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Sample records for chronic mild stress

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

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    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...

  2. 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

  3. Sex differences in the chronic mild stress model of depression.

    Science.gov (United States)

    Franceschelli, Anthony; Herchick, Samantha; Thelen, Connor; Papadopoulou-Daifoti, Zeta; Pitychoutis, Pothitos M

    2014-09-01

    A large volume of clinical and experimental evidence documents sex differences in brain anatomy, chemistry, and function, as well as in stress and drug responses. The chronic mild stress model (CMS) is one of the most extensively investigated animal models of chronic stress. However, only a limited number of studies have been conducted in female rodents despite the markedly higher prevalence of major depression among women. Herein, we review CMS studies conducted in rats and mice of both sexes and further discuss intriguing sex-dependent behavioral and neurobiological findings. The PubMed literature search engine was used to find and collect all relevant articles analyzed in this review. Specifically, a multitermed search was performed with 'chronic mild stress', 'chronic unpredictable stress' and 'chronic variable stress' as base terms and 'sex', 'gender', 'females' and 'depression' as secondary terms in various combinations. Male and female rodents appear to be differentially affected by CMS application, depending on the behavioral, physiological, and neurobiological indices that are being measured. Importantly, the CMS paradigm, despite its limitations, has been successfully used to assess a constellation of interdisciplinary research questions in the sex differences field and has served as a 'silver bullet' in assessing the role of sex in the neurobiology of major depression.

  4. Predictable chronic mild stress in adolescence increases resilience in adulthood.

    Science.gov (United States)

    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

    2013-07-01

    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 adolescent rats (postnatal days (PNDs) 28-55) to test the resilience effect of PCMS on depressive-like behavior in the sucrose preference test and forced swim test and anxiety-like behavior in the novelty-suppressed feeding test and elevated plus maze in adulthood. We also investigated the role of mammalian target of rapamycin (mTOR) signaling in the brain during the PCMS procedure in adolescence. Moreover, we investigated the effect of PCMS in adolescence on subsequent responses to chronic unpredictable stress (CUS; PNDs 63-83) in adulthood. The results demonstrated that PCMS during adolescence produced antidepressant- and anxiolytic-like effects and increased mTOR signaling activity in the prefrontal cortex in early adulthood. Either systemic administration or intra-PFC infusion of the mTOR inhibitor rapamycin completely blocked the behavioral effects produced by PCMS in adolescence. PCMS during adolescence resisted depressive- and anxiety-like behavior caused by CUS in adulthood. These findings indicate that PCMS in adolescence can contribute to resilience against depression and anxiety caused by stress in adulthood.

  5. 3, 4-methylenedioximethamphetamin reverses anxiety induced by chronic mild stress

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    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.

  6. 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.

  7. 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.

  8. 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...

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

    Science.gov (United States)

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

    2015-02-01

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

  10. Chronic unpredictable mild stress generates oxidative stress and systemic inflammation in rats.

    Science.gov (United States)

    López-López, Ana Laura; Jaime, Herlinda Bonilla; Escobar Villanueva, María Del Carmen; Padilla, Malinalli Brianza; Palacios, Gonzalo Vázquez; Aguilar, Francisco Javier Alarcón

    2016-07-01

    Stress is considered to be a causal agent of chronic degenerative diseases, such as cardiovascular disease, diabetes mellitus, arthritis and Alzheimer's. Chronic glucocorticoid and catecholamine release into the circulation during the stress response has been suggested to activate damage mechanisms, which in the long term produce metabolic alterations associated with oxidative stress and inflammation. However, the consequences of stress in animal models for periods longer than 40days have not been explored. The goal of this work was to determine whether chronic unpredictable mild stress (CUMS) produced alterations in the redox state and the inflammatory profile of rats after 20, 40, and 60days. CUMS consisted of random exposure of the animals to different stressors. The following activities were measured in the liver and pancreas: reduced glutathione (GSH), lipid peroxidation (LPO), superoxide dismutase (SOD), catalase (CAT), total antioxidant capacity (TAC), and protein oxidation. Similarly, serum cytokine levels (IL-6, TNF-α, IL-1β, and IL-10) were determined. CUMS activated the stress response from day 20 until day 60. In the liver and pancreas, GHS levels were decreased from day 40, whereas protein lipid peroxidation and protein oxidation were increased. This is the first work to report that the pancreas redox state is subject to chronic stress conditions. The TAC was constant in the liver and reduced in the pancreas. An increase in the TNF-α, IL-1β, and IL-6 inflammatory markers and a decrease in the IL-10 level due to CUMS was shown, thereby resulting in the generation of a systemic inflammation state after 60days of treatment. Together, the CUMS consequences on day 60 suggest that both processes can contribute to the development of chronic degenerative diseases, such as cardiovascular disease and diabetes mellitus. CUMS is an animal model that in addition to avoiding habituation activates damage mechanisms such as oxidative stress and low-grade chronic

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

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    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.

  12. 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...

  13. Cognitive deficits in the rat chronic mild stress model for depression: relation to anhedonic-like responses

    DEFF Research Database (Denmark)

    Henningsen, Kim; Andreasen T., Jesper; Bouzinova, Elena V.

    2009-01-01

    The chronic mild stress (CMS) protocol is widely used to evoke depressive-like behaviours in laboratory rats. The aim of the present study was to examine the effects of chronic stress on cognitive performance. About 70% of rats exposed to 7 weeks of chronic mild stress showed a gradual reduction...... in consumption of a sucrose solution, indicating an anhedonic-like state. The remaining rats did not reduce their sucrose intake, but appeared resilient to the stress-induced effects on sucrose intake. Cognitive profiling of the CMS rats revealed that chronic stress had a negative effect on performance...

  14. The chronic mild stress (CMS) model of depression: History, evaluation and usage.

    Science.gov (United States)

    Willner, Paul

    2017-02-01

    Now 30 years old, the chronic mild stress (CMS) model of depression has been used in >1300 published studies, with a year-on-year increase rising to >200 papers in 2015. Data from a survey of users show that while a variety of names are in use (chronic mild/unpredictable/varied stress), these describe essentially the same procedure. This paper provides an update on the validity and reliability of the CMS model, and reviews recent data on the neurobiological basis of CMS effects and the mechanisms of antidepressant action: the volume of this research may be unique in providing a comprehensive account of antidepressant action within a single model. Also discussed is the use of CMS in drug discovery, with particular reference to hippocampal and extra-hippocampal targets. The high translational potential of the CMS model means that the neurobiological mechanisms described may be of particular relevance to human depression and mechanisms of clinical antidepressant action.

  15. 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......-like response) was reduced in anhedonic rats (p depression-like symptoms are associated with reduced endothelium-dependent relaxation due to suppressed...... endothelium-dependent hyperpolarization-like relaxation despite up-regulation of the NO and COX-2-dependent pathways in rat mesenteric arteries. These changes could affect peripheral resistance and organ perfusion in major depression....

  16. 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...

  17. Influence of housing on the consequences of chronic mild stress in female rats.

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    Baker, S; Bielajew, C

    2007-08-01

    The chronic mild stress (CMS) paradigm was developed to model anhedonia in animals. The repeated administration of a series of unpredictable, mild stressors attempts to mimic the daily stress associated with the onset of clinical depression in humans. Male animals are predominantly used in these investigations despite significant, well-documented sex differences in human depression. In this study, the CMS procedure was modified to be more ecologically relevant to female animals. The effects of stress on sucrose preference, social interaction, rate of weight gain, and regularity of the estrous cycle in female Sprague-Dawley (SD) rats were evaluated in both single- and paired-housed rats, during 3 weeks each of baseline, CMS, and post-CMS phases. The results indicate that only single-housed rats exposed to stressors have a reduced rate of weight gain, significantly attenuated sucrose preference levels, and increased social interaction scores during the CMS phase of the study. Housing condition more than exposure to stress appeared to contribute to the disruption of estrous cycling in some animals. These data suggest that housing affords some protection from the negative consequences of CMS, at least in female rats, and that lack of social interaction in the single-housing condition may render females more vulnerable to stress-related illnesses. The development of paradigms that model human depression should emphasize sex-specific differences.

  18. Sex differences in response to chronic mild stress and congenital serotonin deficiency.

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    Sachs, Benjamin D; Ni, Jason R; Caron, Marc G

    2014-02-01

    Women exhibit a nearly twofold increased risk of developing depression and anxiety disorders when compared to men, a fact that has been hypothesized to result in part from increased stress susceptibility. Here, we used the tryptophan hydroxylase-2 R439H knock-in mouse (Tph2KI) and the chronic unpredictable mild stress (CMS) model to examine sex differences in response to congenital 5-HT deficiency and chronic stress. Our results demonstrate that female mice, but not 5-HT-deficient animals, exhibit significantly increased susceptibility to CMS-induced despair-like behavior in the forced swim test. In addition, female 5-HT-deficient mice exhibit anhedonia-like behavior in the sucrose preference test, whereas male 5-HT-deficient animals do not, suggesting that females exhibit increased sensitivity to at least some of the effects of congenital 5-HT deficiency. Although CMS did not reduce cell proliferation in the hippocampus, low levels of brain 5-HT were associated with increased hippocampal cell proliferation, an effect that was predominantly observed in females. Overall, these results highlight the importance of interactions between psychiatric disease risk factors such as sex, chronic stress and congenital 5-HT deficiency in the development of aberrant emotional behavior.

  19. 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.

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

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    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.

  1. In utero programming alters adult response to chronic mild stress: part 3 of a longitudinal study.

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    Baker, Stephanie L; Mileva, Guergana; Huta, Veronika; Bielajew, Catherine

    2014-11-07

    Exposure to stress before birth may lay the foundation for the development of sensitivities or protection from psychiatric disorders while later stress exposure may trigger either their expression or suppression. This report, part three of a longitudinal study conducted in our laboratory, aimed to examine the interaction between early and adult stress and their effects on measures of anxiety and depression. In parts one and two, we reported the effects of gestational stress (GS) in Long Evans rat dams and their juvenile and young adult offspring. In this third and final installment, we evaluated the effects of GS and chronic mild stress (CMS) in the adult female offspring at 6 month and 12 month time-points. The two by two design included a combination of GS and CMS and the appropriate control groups. Using Hierarchical Linear Modeling, main effects of GS on corticosterone level at the 12 month time-point was found while main effects of CMS were seen in body weight, sucrose preference, and corticosterone, and significant interactions between group at the 6 and 12 month time-points. The GS group had the lowest sucrose preference during CMS at 6 months supporting a cumulative effect of early and later life stress. The GS/CMS group showed lower corticosterone at 12 months than the GS/noCMS group indicating a possible mismatch between prenatal programming and later life stress. These results highlight the importance of early life factors in exerting potentially protective effects in models involving later life stress.

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

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    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.

  3. DISTURBANCES OF BIOLOGICAL RHYTHMS IN A RAT CHRONIC MILD STRESS MODEL OF DEPRESSION

    DEFF Research Database (Denmark)

    Christiansen, Sofie; Wiborg, Ove; Bouzinova, Elena

    Aim: The focus of this project is to identify biomarkers related to circadian disturbances in major depressive disorder. Background: A large body of clinical data from depressed individuals showed that sleep, temperature, hormones, physiological states and moodchanges are consistent...... validated animal model of depression, the chronic mild stress model (CMS). Depression-like and control rats were killed by decapitation within 24 h. Trunk blood, brain and liver tissue were collected. The quantitative amount of plasma corticosterone and melatonin were measured using an ELISA and RIA kit...... that depression-like animals showed an abnormal circadian rhythm in the liver and in subregions of the rat brains related to depression. However, the SCN was partly protected against stress. We found an increased level of corticosteron and melatonin, in the depression-like animals as well as a shifted circadian...

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

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

    2013-12-03

    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.

  5. Chronic mild stress damages mitochondrial ultrastructure and function in mouse brain.

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    Gong, Yu; Chai, Yi; Ding, Jian-Hua; Sun, Xiu-Lan; Hu, Gang

    2011-01-13

    Increasing evidence implicates mitochondrial failure as a crucial factor in the pathogenesis of mental disorders, such as depression. The aim of the present study was to investigate the effects of exposure to chronic mild stress (CMS), a paradigm developed in the late 1980s as an animal model of depression, on the mitochondrial function and mitochondrial ultrastructure in the mouse brain. The results showed that the CMS regime induced depressive-like symptoms in mice characterized by reduced sucrose preference and body weight. Moreover, CMS exposure was associated with a significant increase in immobility time in the tail suspension test. Exposure to the CMS paradigm inhibited mitochondrial respiration rates and dissipated mitochondrial membrane potential in hippocampus, cortex and hypothalamus of mice. In addition, we found a damaged mitochondrial ultrastructure in brains of mice exposed to CMS. These findings provide evidence for brain mitochondrial dysfunction and ultrastructural damage in a mouse model of depression. Moreover, these findings suggest that mitochondrial malfunction-induced oxidative injury could play a role in stress-related disorders such as depression.

  6. The link between unpredictable chronic mild stress model for depression and vascular inflammation?

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    Demirtaş, Tuğçe; Utkan, Tijen; Karson, Ayşe; Yazır, Yusufhan; Bayramgürler, Dilek; Gacar, Nejat

    2014-10-01

    Inflammation has been suggested to be associated with stress-induced depression and cardiovascular dysfunction. Tumor necrosis factor alpha (TNF-α) is a major cytokine in the activation of neuroendocrine, immune, and behavioral responses. In this study, we investigated the effects of infliximab (a TNF-α inhibitor) on endothelium-dependent vascular reactivity, systemic blood pressure, and endothelial nitric oxide synthase (eNOS) immunoreactivity in the unpredictable chronic mild stress (UCMS) model of depression in rats. There was no significant change between all groups in the systemic blood pressure. In UCMS, endothelium-dependent relaxation of the smooth muscle in response to carbachol was significantly decreased with 50 % maximal response (E max) and pD2 values compared with the controls. Infliximab was able to reverse this UCMS effect. Relaxation in response to the nitric oxide (NO) donor sodium nitroprusside and papaverine and KCl-induced contractile responses was similar between groups. In UCMS, decreased expression of eNOS was detected. Moreover, there was no significant change in UCMS + infliximab group with respect to control rats. Our results suggest that tumor necrosis factor-alpha (TNF-α) could be a major mediator of vascular dysfunction associated with UCMS, leading to decreased expression of eNOS.

  7. 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.

  8. Effects of fluoxetine on protein expression of potassium ion channels in the brain of chronic mild stress rats

    OpenAIRE

    Chunlin Chen; Ling Wang; Xianfang Rong; Weiping Wang; Xiaoliang Wang

    2015-01-01

    The purpose of this study is to investigate the expression of major potassium channel subtypes in the brain of chronical mild stress (CMS) rats and reveal the effects of fluoxetine on the expression of these channels. Rats were exposed to a variety of unpredictable stress for three weeks and induced anhedonia, lower sucrose preference, locomotor activity and lower body weight. The protein expressions were determined by Western blot. CMS significantly increased the expression of Kv2.1 channel ...

  9. Effects of chronic mild stress on behavioral and neurobiological parameters - Role of glucocorticoid.

    Science.gov (United States)

    Chen, Jiao; Wang, Zhen-zhen; Zuo, Wei; Zhang, Shuai; Chu, Shi-feng; Chen, Nai-hong

    2016-02-01

    Major depression is thought to originate from maladaptation to adverse events, particularly when impairments occur in mood-related brain regions. Hypothalamus-pituitary-adrenal (HPA) axis is one of the major systems involved in physiological stress response. HPA axis dysfunction and high glucocorticoid concentrations play an important role in the pathogenesis of depression. In addition, astrocytic disability and dysfunction of neurotrophin brain-derived neurotrophin factor (BDNF) greatly influence the development of depression and anxiety disorders. Therefore, we investigated whether depressive-like and anxiety-like behaviors manifest in the absence of glucocorticoid production and circulation in adrenalectomized (ADX) rats after chronic mild stress (CMS) exposure and its potential molecular mechanisms. The results demonstrate that glucocorticoid-controlled rats showed anxiety-like behaviors but not depression-like behaviors after CMS. Molecular and cellular changes included the decreased BDNF in the hippocampus, astrocytic dysfunction with connexin43 (cx43) decreasing and abnormality in gap junction in prefrontal cortex (PFC). Interestingly, we did not find any changes in glucocorticoid receptor (GR) or its chaperone protein FK506 binding protein 51 (FKBP5) expression in the hippocampus or PFC in ADX rats subjected to CMS. In conclusion, the production and circulation of glucocorticoids are one of the contributing factors in the development of depression-like behaviors in response to CMS. In contrast, the effects of CMS on anxiety-like behaviors are independent of the presence of circulating glucocorticoids. Meanwhile, stress decreased GR expression and enhanced FKBP5 expression via higher glucocorticoid exposure. Gap junction dysfunction and changes in BDNF may be associated with anxiety-like behaviors.

  10. Peptide Selank Enhances the Effect of Diazepam in Reducing Anxiety in Unpredictable Chronic Mild Stress Conditions in Rats

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    Kolomin, Timur; Andreeva, Lyudmila; Bondarenko, Elena; Myasoedov, Nikolay; Slominsky, Petr; Shadrina, Maria

    2017-01-01

    It was shown that the anxiolytic effect of Selank is comparable to that of classical benzodiazepine drugs and that the basis of their mechanism of action may be similar. These data suggest that the presence of Selank may change the action of classical benzodiazepine drugs. To test this hypothesis, we evaluated the anxiolytic activity of Selank and diazepam in rats both under conditions of unpredictable chronic mild stress and in its absence, after the individual and combined administration of these compounds using the elevated plus maze test. We found that, even in the absence of chronic stress, the administration of a course of test substances changed anxiety indicators toward their deterioration, but the changes after the administration of a course of Selank were less pronounced. In conditions of chronic stress, anxiety indicator values after the simultaneous use of diazepam and Selank did not differ from the respective values observed before chronic stress exposure. The data obtained indicate that the individual administration of Selank was the most effective in reducing elevated levels of anxiety, induced by the administration of a course of test substances, whereas the combination of diazepam with Selank was the most effective in reducing anxiety in unpredictable chronic mild stress conditions. PMID:28280289

  11. Simvastatin treatment exerts antidepressant-like effect in rats exposed to chronic mild stress.

    Science.gov (United States)

    Lin, Pao-Yen; Chang, Alice Y W; Lin, Tsu-Kung

    2014-09-01

    Hyperlipidemia is associated with increased risk of coronary artery disease and stroke, both of which, in turn, are risk factors of old-age depression. Statins are extensively used for decreasing cholesterol levels. Clinical investigations revealed that long-term use of statins appeared to be associated with a lower risk of anxiety and depression. However, the antidepressant property of statins has not been well examined. This study aimed at examining the antidepressant-like effects of statins in rats exposed to chronic mild stress (CMS). We found that animals exposed to CMS for 4 weeks developed depressive-like state, shown by forced swim test and sucrose preference test. However, these CMS-induced behavioral changes were reversed by simvastatin (5 or 10mg/kg/day) for 14 days, comparable to imipramine (10mg/kg/day) treatment. Locomotor activity and anxiety-like behaviors were not altered by CMS or these treatments. These results demonstrated antidepressant-like effects of statin in CMS model of rats and suggested the potential that statins could be used to facilitate antidepressant treatment in clinical setting.

  12. Chronic unpredictive mild stress leads to altered hepatic metabolic profile and gene expression.

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    Jia, Hong-Mei; Li, Qi; Zhou, Chao; Yu, Meng; Yang, Yong; Zhang, Hong-Wu; Ding, Gang; Shang, Hai; Zou, Zhong-Mei

    2016-03-23

    Depression is a complex disease characterized by a series of pathological changes. Research on depression is mainly focused on the changes in brain, but not on liver. Therefore, we initially explored the metabolic profiles of hepatic extracts from rats treated with chronic unpredictive mild stress (CUMS) by UPLC-Q-TOF/MS. Using multivariate statistical analysis, a total of 26 altered metabolites distinguishing CUMS-induced depression from normal control were identified. Using two-stage receiver operating characteristic (ROC) analysis, 18 metabolites were recognized as potential biomarkers related to CUMS-induced depression via 12 metabolic pathways. Subsequently, we detected the mRNA expressions levels of apoptosis-associated genes such as Bax and Bcl-2 and four key enzymes including Pla2g15, Pnpla6, Baat and Gad1 involved in phospholipid and primary bile acid biosynthesis in liver tissues of CUMS rats by real-time qRT-PCR assay. The expression levels of Bax, Bcl-2, Pla2g15, Pnpla6 and Gad1 mRNA were 1.43,1.68, 1.74, 1.67 and 1.42-fold higher, and those of Baat, Bax/Bcl-2 ratio mRNA were 0.83, 0.85-fold lower in CUMS rats compared with normal control. Results of liver-targeted metabonomics and mRNA expression demonstrated that CUMS-induced depression leads to variations in hepatic metabolic profile and gene expression, and ultimately results in liver injury.

  13. 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.

  14. Neurocircuitry underlying stress and emotional regulation in animals prenatally exposed to alcohol and subjected to chronic mild stress in adulthood

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    Charlis eRaineki

    2014-02-01

    Full Text Available Individuals exposed to alcohol during gestation show higher rates of psychopathologies. The hyperresponsivity to stress induced by prenatal alcohol exposure may be related to this increased rate of psychopathologies, especially because this population is more likely to be exposed to stressful environments throughout life. However, alcohol-induced changes in the overlapping neurocircuitries that underlie stress and the expression of psychopathologies are not fully understood. Here, we performed a comprehensive analysis of the neural activity within central areas known to play key roles in both emotional and stress regulation. Adult male and female offspring from prenatal alcohol exposure (PAE, pair-fed, and ad libitum-fed control conditions were exposed to chronic mild stress (CMS. Following CMS, the neural activity (c-fos mRNA of the amygdala, ventral hippocampal formation, medial prefrontal cortex (mPFC, and paraventricular nucleus of hypothalamus (PVN was assessed in response to an acute stress (elevated plus maze. Our results demonstrate that, overall, PAE decreased neural activity within the amygdala and hippocampal formation in males and increased neural activity within the amygdala and mPFC in females. CMS reduced neural activity within the mPFC and PVN in PAE males, but reduced activity in all areas analyzed in control males. By contrast, CMS reduced neural activity in the mPFC in PAE females and had no effects in control females. Furthermore, the constrained principal component analysis revealed that these patterns of neural activity resulted in differential activation of functional neural networks in males compared to females, indicating sexually dimorphic effects of PAE and CMS. Importantly, the altered networks of brain activation in PAE animals may underlie the hyperresponsivity to stress and increased psychopathologies observed among individuals prenatally exposed to alcohol.

  15. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

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    Khedr LH

    2015-11-01

    Full Text Available Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chronic mild stress (CMS model and changes in hippocampal energy metabolism and the role of paroxetine (PAROX in ameliorating these changes. Male Wistar rats were divided into three groups: vehicle control, CMS-exposed rats, and CMS-exposed rats receiving PAROX (10 mg/kg/day intraperitoneally. Sucrose preference, open-field, and forced swimming tests were carried out. Corticosterone (CORT was measured in serum, while adenosine triphosphate and its metabolites, cytosolic cytochrome-c (Cyt-c, caspase-3 (Casp-3, as well as nitric oxide metabolites (NOx were measured in hippocampal tissue homogenates. CMS-exposed rats showed a decrease in sucrose preference as well as body weight compared to control, which was reversed by PAROX. The latter further ameliorated the CMS-induced elevation of CORT in serum (91.71±1.77 ng/mL vs 124.5±4.44 ng/mL, P<0.001 as well as the changes in adenosine triphosphate/adenosine diphosphate (3.76±0.02 nmol/mg protein vs 1.07±0.01 nmol/mg protein, P<0.001. Furthermore, PAROX reduced the expression of Cyt-c and Casp-3, as well as restoring NOx levels. This study highlights the role of PAROX in reversing depressive behavior associated with stress-induced apoptosis and changes in hippocampal energy metabolism in the CMS model of depression. Keywords: rats, CMS, hippocampus, paroxetine, apoptosis, adenine nucleotides, cytochrome-c, caspase-3

  16. 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

    mild stress and chronic escitalopram treatment. Furthermore, we investigated which classes of immature granule cells are affected by stress and targeted by escitalopram. Rats were initially exposed to 2weeks of CMS and 4weeks of escitalopram treatment with concurrent exposure to stress. The behavioral...... 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......, but not in the rats that did not respond to escitalopram treatment. These changes were not followed by alterations in the volume of the granule cell layer. We also showed a differential regulation of dentate neurons, in different stages of development, by chronic stress and chronic escitalopram treatment. Our study...

  17. 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.

  18. 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...

  19. Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced...... anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d...... changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy....

  20. Summary of high field diffusion MRI and microscopy data demonstrate microstructural aberration in chronic mild stress rat brain

    DEFF Research Database (Denmark)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove

    2016-01-01

    Abstract This data article describes a large, high resolution diffusion MRI data set from fixed rat brain acquired at high field strength. The rat brain samples consist of21adult rat brain hemispheres from animals exposed to chronic mild stress (anhedonic and resilient) and controls. Histology from...... amygdala of the same brain hemispheres is also included with three different stains: DiI and Hoechst stained microscopic images (confocal microscopy) andALDH1L1 antibody based immunohistochemistry.These stains may be used to evaluate neurite density (DiI), nuclear density (Hoechst) and astrocytic density...

  1. Adaptive response to chronic mild ethanol stress involves ROS, sirtuins and changes in chromosome dosage in wine yeasts.

    Science.gov (United States)

    Adamczyk, Jagoda; Deregowska, Anna; Skoneczny, Marek; Skoneczna, Adrianna; Kwiatkowska, Aleksandra; Potocki, Leszek; Rawska, Ewa; Pabian, Sylwia; Kaplan, Jakub; Lewinska, Anna; Wnuk, Maciej

    2016-05-24

    Industrial yeast strains of economic importance used in winemaking and beer production are genomically diverse and subjected to harsh environmental conditions during fermentation. In the present study, we investigated wine yeast adaptation to chronic mild alcohol stress when cells were cultured for 100 generations in the presence of non-cytotoxic ethanol concentration. Ethanol-induced reactive oxygen species (ROS) and superoxide signals promoted growth rate during passages that was accompanied by increased expression of sirtuin proteins, Sir1, Sir2 and Sir3, and DNA-binding transcription regulator Rap1. Genome-wide array-CGH analysis revealed that yeast genome was shaped during passages. The gains of chromosomes I, III and VI and significant changes in the gene copy number in nine functional gene categories involved in metabolic processes and stress responses were observed. Ethanol-mediated gains of YRF1 and CUP1 genes were the most accented. Ethanol also induced nucleolus fragmentation that confirms that nucleolus is a stress sensor in yeasts. Taken together, we postulate that wine yeasts of different origin may adapt to mild alcohol stress by shifts in intracellular redox state promoting growth capacity, upregulation of key regulators of longevity, namely sirtuins and changes in the dosage of genes involved in the telomere maintenance and ion detoxification.

  2. Resveratrol exerts anti-inflammatory and neuroprotective effects to prevent memory deficits in rats exposed to chronic unpredictable mild stress.

    Science.gov (United States)

    Yazir, Yusufhan; Utkan, Tijen; Gacar, Nejat; Aricioglu, Feyza

    2015-01-01

    A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation.

  3. 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

  4. Chronic mild stress and imipramine treatment elicit opposite changes in behavior and in gene expression in the mouse prefrontal cortex.

    Science.gov (United States)

    Erburu, M; Cajaleon, L; Guruceaga, E; Venzala, E; Muñoz-Cobo, I; Beltrán, E; Puerta, E; Tordera, R M

    2015-08-01

    Many studies suggest that the prefrontal cortex (PFC) is a target limbic region for stress response because a dysfunction here is linked to anhedonia, a decrease in reactivity to rewards, and to anxiety. It is suggested that stress-induced persistent molecular changes in this brain region could bring some light on the mechanisms perpetuating depressive episodes. In order to address this issue, here we have studied the long-term PFC gene expression pattern and behavioral effects induced by a chronic mild stress (CMS) model and antidepressant treatment in mice. CMS was applied to mice for six weeks and imipramine (10mg/kg, i.p.) or saline treatment was administered for five weeks starting from the third week of CMS. Mice were sacrificed one month after CMS and following two weeks after the discontinuation of drug treatment and the PFC was dissected and prepared for gene (mRNA) and protein expression studies. Using the same experimental design, a separate group of mice was tested for anhedonia, recognition memory, social interaction and anxiety. CMS induced a long-term altered gene expression profile in the PFC that was partially reverted by imipramine. Specifically, the circadian rhythm signaling pathway and functions such as gene expression, cell proliferation, survival and apoptosis as well as neurological and psychiatric disorders were affected. Of these, some changes of the circadian rhythm pathway (Hdac5, Per1, and Per2) were validated by RT-PCR and western-blot. Moreover, CMS induced long-lasting anhedonia that was reverted by imipramine treatment. Impaired memory, decreased social interaction and anxiety behavior were also induced by chronic stress. We have identified in the PFC molecular targets oppositely regulated by CMS and imipramine that could be relevant for chronic depression and antidepressant action. Among these, a possible candidate for further investigation could be the circadian rhythm pathway.

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

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    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.

  6. Thymol produces an antidepressant-like effect in a chronic unpredictable mild stress model of depression in mice.

    Science.gov (United States)

    Deng, Xue-Yang; Li, Hong-Yan; Chen, Jun-Jun; Li, Rui-Peng; Qu, Rong; Fu, Qiang; Ma, Shi-Ping

    2015-09-15

    Thymol, a bioactive monoterpene isolated from Thymus vulgaris, has displayed inspiring neuroprotective properties. The present study was designed to evaluate the antidepressant-like effects of thymol on a chronic unpredictable mild stress (CUMS) model of depression in mice and explore the underlying mechanisms. It was observed that thymol treatment (15 mg/kg and 30 mg/kg) significantly reversed the decrease of sucrose consumption, the loss of body weight, the reduction of immobile time in the tail suspension tests (TST) and forced swimming tests (FST) induced by CUMS paradigm. The levels of norepinephrine (NE) and serotonin (5-HT) in the hippocampus decreased in the CUMS-treated mice. Chronic treatments with thymol significantly restored the CUMS-induced alterations of monoamine neurotransmitters in the hippocampus. Our results further demonstrated that thymol administration negatively regulated the induction of proinflammatory cytokines including interleukin (IL)-1β, IL-6, and tumor necrosis factor-α in CUMS mice. Furthermore, thymol inhibited the activation of nod-like receptor protein 3 (NLRP3) inflammasome and its adaptor, and subsequently decreased the expression of caspase-1. In sum, our findings suggested that thymol played a potential antidepressant role in CUMS mice model through up-regulating the levels of central neurotransmitters and inhibiting the expressions of proinflammatory cytokines, which might provide potential for thymol in the light of opening up new therapeutic avenues for depression.

  7. Effects of prenatal exposure to a mild chronic variable stress on body weight, preweaning mortality and rat behavior

    Directory of Open Access Journals (Sweden)

    Cabrera R.J.

    1999-01-01

    Full Text Available Early stimulation has been shown to produce long-lasting effects in many species. Prenatal exposure to some strong stressors may affect development of the nervous system leading to behavioral impairment in adult life. The purpose of the present work was to study the postnatal harmful effects of exposure to variable mild stresses in rats during pregnancy. Female Holtzman rats were submitted daily to one session of a chronic variable stress (CVS during pregnancy (prenatal stress; PS group. Control pregnant rats (C group were undisturbed. The pups of PS and C dams were weighed and separated into two groups 48 h after delivery. One group was maintained with their own dams (PS group, N = 70; C group, N = 36 while the other PS pups were cross-fostered with C dams (PSF group, N = 47 and the other C pups were cross-fostered with PS dams (CF group, N = 58. Pups were undisturbed until weaning (postnatal day 28. The male offspring underwent motor activity tests (day 28, enriched environment tests (day 37 and social interaction tests (day 42 in an animal activity monitor. Body weight was recorded on days 2, 28 and 60. The PS pups showed lower birth weight than C pups (Duncan's test, P<0.05. The PS pups suckling with their stressed mothers displayed greater preweaning mortality (C: 23%, PS: 60%; c2 test, P<0.05 and lower body weight than controls at days 28 and 60 (Duncan's test, P<0.05 and P<0.01, respectively. The PS, PSF and CF groups showed lower motor activity scores than controls when tested at day 28 (Duncan's test, P<0.01 for PS group and P<0.05 for CF and PSF groups. In the enriched environment test performed on day 37, between-group differences in total motor activity were not detected; however, the PS, CF and PSF groups displayed less exploration time than controls (Duncan's test, P<0.05. Only the PS group showed impaired motor activity and impaired social behavior at day 42 (Duncan's test, P<0.05. In fact, CVS treatment during gestation plus

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

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    Min Hu

    2016-01-01

    Full Text Available 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.

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

    DEFF Research Database (Denmark)

    Hougaard, K. S.; Andersen, Maud Bering; Hansen, A. M.;

    2005-01-01

    function due to CMS were observed. In the present experimental setting, there was no indication of the two exposures potentiating each other with respect to adverse effects on the nervous system. However, the effects of prenatal CMS indicate that stress during fetal life may interfere with the development...

  10. Paroxetine ameliorates changes in hippocampal energy metabolism in chronic mild stress-exposed rats

    OpenAIRE

    Khedr LH; Nassar NN; El-Denshary ES; Abdel-tawab AM

    2015-01-01

    Lobna H Khedr, Noha N Nassar, Ezzeldin S El-Denshary, Ahmed M Abdel-tawab 1Department of Pharmacology, Faculty of Pharmacy, Misr International University, 2Department of Pharmacology, Faculty of Pharmacy, Cairo University, 3Department of Pharmacology, Faculty of Medicine, Ain Shams University, Cairo, Egypt Abstract: The molecular mechanisms underlying stress-induced depression have not been fully outlined. Hence, the current study aimed at testing the link between behavioral changes in chro...

  11. Antidepressant Effects of Aripiprazole Augmentation for Cilostazol-Treated Mice Exposed to Chronic Mild Stress after Ischemic Stroke

    Science.gov (United States)

    Kim, Yu Ri; Kim, Ha Neui; Hong, Ki Whan; Shin, Hwa Kyoung; Choi, Byung Tae

    2017-01-01

    The aim of this study was to determine the effects and underlying mechanism of aripiprazole (APZ) augmentation for cilostazol (CLS)-treated post-ischemic stroke mice that were exposed to chronic mild stress (CMS). Compared to treatment with either APZ or CLS alone, the combined treatment resulted in a greater reduction in depressive behaviors, including anhedonia, despair-like behaviors, and memory impairments. This treatment also significantly reduced atrophic changes in the striatum, cortex, and midbrain of CMS-treated ischemic mice, and inhibited neuronal cell apoptosis, particularly in the striatum and the dentate gyrus of the hippocampus. Greater proliferation of neuronal progenitor cells was also observed in the ipsilateral striatum of the mice receiving combined treatment compared to mice receiving either drug alone. Phosphorylation of the cyclic adenosine monophosphate response element binding protein (CREB) was increased in the striatum, hippocampus, and midbrain of mice receiving combined treatment compared to treatment with either drug alone, particularly in the neurons of the striatum and hippocampus, and dopaminergic neurons of the midbrain. Our results suggest that APZ may augment the antidepressant effects of CLS via co-regulation of the CREB signaling pathway, resulting in the synergistic enhancement of their neuroprotective effects. PMID:28208711

  12. 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.

  13. Iptakalim confers an antidepressant effect in a chronic mild stress model of depression through regulating neuro-inflammation and neurogenesis.

    Science.gov (United States)

    Lu, Ming; Yang, Jing-Zhe; Geng, Fan; Ding, Jian-Hua; Hu, Gang

    2014-09-01

    Depression is a serious mental disorder in the world, but the underlying mechanisms remain unclear and the effective cures are scarce. Iptakalim (Ipt), an ATP-sensitive potassium (K-ATP) channel opener that can cross the blood-brain barrier freely, has been demonstrated to inhibit neuro-inflammation and enhance adult hippocampal neurogenesis. But it is unknown whether Ipt is beneficial to therapy of depression by modulating neurogenesis and neuro-inflammation. This study aimed to determine the potential antidepressant efficacy of Ipt in a chronic mild stress (CMS) mouse model of depression. We showed that treatment with Ipt (10 mg/kg/day, i.p) for 4 wk restored the decrease of sucrose preference and shortened the immobile time in forced swimming tests (FST) and tail suspension tests (TST) in CMS model mice. We further found that Ipt reversed the CMS-induced reduction of the adult hippocampal neurogenesis and improved cerebral insulin signalling in the CMS mice. Furthermore, Ipt negatively regulated nod-like receptor protein 3 (NLRP3) expression and, in turn, inhibited microglia-mediated neuro-inflammation by suppressing the activation of NLRP3-inflammasome/caspase-1/interleukin 1β axis in the hippocampus of CMS mice. Taken together, our findings demonstrate that Ipt plays a potential antidepressant role in CMS model mice through regulating neuro-inflammation and neurogenesis, which will provide potential for Ipt in terms of opening up novel therapeutic avenues for depression.

  14. 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.

  15. Antidepressant-like effects of Sanyuansan in the mouse forced swim test, tail suspension test, and chronic mild stress model.

    Science.gov (United States)

    Yan, Shuo; You, Zi-Li; Zhao, Qiu-Ying; Peng, Cheng; He, Gang; Gou, Xiao-Jun; Lin, Bin

    2015-12-01

    Natural products have been widely reported as effective therapeutic alternatives for treatment of depression. Sanyuansan is a compound recipe composed of ginseng total saponins, fish oil, and valeriana. The aims of this study were to validate whether Sanyuansan has antidepressant-like effects through acute behavioral tests including the forced swimming test (FST), tail suspension test (TST), locomotor activity test, and chronic mild stress (CMS) mice model of depression. C57BL/6 mice were given oral administration of 30 mg/kg imipramine, Sanyuansan, and saline, respectively. The acute behavioral tests including the TST, FST, and locomotor activity test were done after the administration of drugs for consecutively three times (24 hours, 1 hour, and 0.5 hour prior to the tests). Furthermore, the sucrose preference and the serum corticosterone level of mice in the CMS model were examined. Sanyuansan only at 900 mg/kg markedly reduced immobility time in the TST compared with the saline-treated group of mice. Sanyuansan at doses of 225 mg/kg, 450 mg/kg, and 900 mg/kg significantly reduced immobility time of mice in the FST. Sanyuansan reversed the CMS-induced anhedonia and hyperactivation of the hypothalamus-pituitary-adrenal axis. In addition, our results showed that neither imipramine nor Sanyuansan at any dosage increased spontaneous motor activity. These results suggested that Sanyuansan induced significant antidepressant-like effects in mice in both acute and chronic animal models, which seemed unlikely to be attributed to an increase in locomotor activities of mice, and had no sedative-like effects.

  16. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice.

    Science.gov (United States)

    Kurhe, Yeshwant; Mahesh, Radhakrishnan

    2016-06-01

    Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ) agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS) induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD) for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o.)/escitalopram (10 mg/kg p.o.)/vehicle (10 ml/kg p.o.) daily from day 15-28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST), tail suspension test (TST) and elevated plus maze (EPM) were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  17. Biophysical modeling of high field diffusion MRI demonstrates micro-structural aberration in chronic mild stress rat brain.

    Science.gov (United States)

    Khan, Ahmad Raza; Chuhutin, Andrey; Wiborg, Ove; Kroenke, Christopher D; Nyengaard, Jens R; Hansen, Brian; Jespersen, Sune Nørhøj

    2016-11-15

    Depression is one of the leading causes of disability worldwide. Immense heterogeneity in symptoms of depression causes difficulty in diagnosis, and to date, there are no established biomarkers or imaging methods to examine depression. Unpredictable chronic mild stress (CMS) induced anhedonia is considered to be a realistic model of depression in studies of animal subjects. Stereological and neuronal tracing techniques have demonstrated persistent remodeling of microstructure in hippocampus, prefrontal cortex and amygdala of CMS brains. Recent developments in diffusion MRI (d-MRI) analyses, such as neurite density and diffusion kurtosis imaging (DKI), are able to capture microstructural changes and are considered to be robust tools in preclinical and clinical imaging. The present study utilized d-MRI analyzed with a neurite density model and the DKI framework to investigate microstructure in the hippocampus, prefrontal cortex, caudate putamen and amygdala regions of CMS rat brains by comparison to brains from normal controls. To validate findings of CMS induced microstructural alteration, histology was performed to determine neurite, nuclear and astrocyte density. d-MRI based neurite density and tensor-based mean kurtosis (MKT) were significantly higher, while mean diffusivity (MD), extracellular diffusivity (Deff) and intra-neurite diffusivity(DL) were significantly lower in the amygdala of CMS rat brains. Deff was also significantly lower in the hippocampus and caudate putamen in stressed groups. Histological neurite density corroborated the d-MRI findings in the amygdala and reductions in nuclear and astrocyte density further buttressed the d-MRI results. The present study demonstrated that the d-MRI based neurite density and MKT can reveal specific microstructural changes in CMS rat brains and these parameters might have value in clinical diagnosis of depression and for evaluation of treatment efficacy.

  18. Pioglitazone, a PPARγ agonist rescues depression associated with obesity using chronic unpredictable mild stress model in experimental mice

    Directory of Open Access Journals (Sweden)

    Yeshwant Kurhe

    2016-06-01

    Full Text Available Pioglitazone, a peroxisome proliferator activated receptor gamma (PPARγ agonist belonging to thiazolidinedione class, is mainly used in diabetes mellitus. Obese subjects are twice likely to become depressed than non-obese individuals. The biological mechanisms linking depression with obesity still remain poorly understood and there is immense need for better therapeutic intervention against such co-morbid disorders. The present study investigates the effect of pioglitazone on the chronic unpredictable mild stress (CUMS induced depression in obese mice by using behavioral tests and biochemical estimations. Mice were fed with high fat diet (HFD for 14 weeks and were further subjected to different stress procedures for 28 days to induce depressive behavior. Animals were administered orally with pioglitazone (30 mg/kg p.o./escitalopram (10 mg/kg p.o./vehicle (10 ml/kg p.o. daily from day 15–28. Various behavioral paradigms such as sucrose preference test, forced swim test (FST, tail suspension test (TST and elevated plus maze (EPM were performed. Biochemical estimations including plasma glucose, total cholesterol, triglycerides, and total proteins were performed. The data obtained from behavioral assays and biochemical assessments indicated that obese animals exhibited severe depressive-like behavior compared to non-obese animals. Furthermore, obese animals subjected to CUMS worsen the depressive behavior compared to obese control animals. Repetitive treatment with pioglitazone reversed the CUMS induced behavioral and biochemical alterations in HFD fed obese mice which atleast in part may be mediated through improving altered plasma glucose. The study suggests that pioglitazone needs further attention with respect to molecular mechanisms that could provide a better therapeutic strategy against depression associated with obesity.

  19. Effect of fluoxetine and resveratrol on testicular functions and oxidative stress in a rat model of chronic mild stress-induced depression.

    Science.gov (United States)

    Sakr, H F; Abbas, A M; Elsamanoudy, A Z; Ghoneim, F M

    2015-08-01

    Our objective was to investigate the effects of chronic unpredictable mild stress (CUMS) with or without selective serotonin reuptake inhibitor (fluoxetine) and anti-oxidant (resveratrol) on testicular functions and oxidative stress in rats. Fifty male rats were divided into 2 groups; control and CUMS. CUMS group was further subdivided into 4 subgroups administered water, fluoxetine, resveratrol and both. Sucrose intake, body weight gain, serum corticosterone, serotonin and testosterone levels, sperm count and motility, testicular malondialdehyde, superoxide dismutase (SOD), catalase, glutathione (GSH), and gene expression of steroidogenic acute-regulatory (StAR) protein and cytochrome P450 side chain cleavage (P450scc) enzyme were evaluated. CUMS decreased sucrose intake, weight gain, anti-oxidants (SOD, catalase, GSH), testosterone, serotonin, StAR and cytochrome P450scc gene expression, sperm count and motility and increased malondialdehyde and corticosterone. Fluoxetine increased malondialdehyde, sucrose intake, weight gain, serotonin and decreased anti-oxidants, StAR and cytochrome P450scc gene expression, sperm count and motility, testosterone, corticosterone in stressed rats. Administration of resveratrol increased anti-oxidants, sucrose intake, weight gain, serotonin, StAR and cytochrome P450scc gene expression, testosterone, sperm count and motility, and decreased malondialdehyde and corticosterone in stressed rats with or without fluoxetine. In conclusion, CUMS induces testicular dysfunctions and oxidative stress. While treatment of CUMS rats with fluoxetine decreases the depressive behavior, it causes further worsening of testicular dysfunctions and oxidative stress. Administration of resveratrol improves testicular dysfunctions and oxidative stress that are caused by CUMS and further worsened by fluoxetine treatment.

  20. Sex-specific effects of prenatal chronic mild stress on adult spatial learning capacity and regional glutamate receptor expression profiles.

    Science.gov (United States)

    Wang, Yan; Ma, Yuchao; Hu, Jingmin; Zhang, Xinxin; Cheng, Wenwen; Jiang, Han; Li, Min; Ren, Jintao; Zhang, Xiaosong; Liu, Mengxi; Sun, Anji; Wang, Qi; Li, Xiaobai

    2016-07-01

    Both animal experiments and clinical studies have demonstrated that prenatal stress can cause cognitive disorders in offspring. To explore the scope of these deficits and identify potential underlying mechanisms, we examined the spatial learning and memory performance and glutamate receptor (GluR) expression patterns of adult rats exposed to prenatal chronic mild stress (PCMS). Principal component analysis (PCA) was employed to reveal the interrelationships among spatial learning indices and GluR expression changes. Female PCMS-exposed offspring exhibited markedly impaired spatial learning and memory in the Morris water maze (MWM) task compared to control females, while PCMS-exposed males showed better initial spatial learning in the MWM compared to control males. PCMS also altered basal and post-MWM glutamate receptor expression patterns, but these effects differed markedly between sexes. Male PCMS-exposed offspring exhibited elevated basal expression of NR1, mGluR5, and mGluR2/3 in the prefrontal cortex (PFC), whereas females showed no basal expression changes. Following MWM training, PCMS-exposed males expressed higher NR1 in the PFC and mammillary body (MB), higher mGluR2/3 in PFC, and lower NR2B in the hippocampus (HIP), PFC, and MB compared to unstressed MWM-trained males. Female PCMS-exposed offspring showed strongly reduced NR1 in MB and NR2B in the HIP, PFC, and MB, and increased mGluR2/3 in PFC compared to unstressed MWM-trained females. This is the first report suggesting that NMDA subunits in the MB are involved in spatial learning. Additionally, PCA further suggests that the NR1-NR2B form is the most important for spatial memory formation. These results reveal long-term sex-specific effects of PCMS on spatial learning and memory performance in adulthood and implicate GluR expression changes within HIP, PFC, and MB as possible molecular mechanisms underlying cognitive dysfunction in offspring exposed to prenatal stress.

  1. Antidepressant-like activity of magnesium in the chronic mild stress model in rats: alterations in the NMDA receptor subunits.

    Science.gov (United States)

    Pochwat, Bartłomiej; Szewczyk, Bernadeta; Sowa-Kucma, Magdalena; Siwek, Agata; Doboszewska, Urszula; Piekoszewski, Wojciech; Gruca, Piotr; Papp, Mariusz; Nowak, Gabriel

    2014-03-01

    Recent data suggests that the glutamatergic system is involved in the pathophysiology and treatment of major depressive disorder (MDD) and that the N-methyl-D-aspartate (NMDA) receptor is a potential target for antidepressant drugs. The magnesium ion blocks the ion channel of the NMDA receptor and prevents its excessive activation. Some preclinical and clinical evidence suggests also that magnesium may be useful in the treatment of depression. The present study investigated the effect of magnesium treatment (10, 15 and 20 mg/kg, given as magnesium hydroaspartate) in the chronic mild stress (CMS) model of depression in rats. Moreover, the effect of CMS and magnesium (with an effective dose) on the level of the proteins related to the glutamatergic system (GluN1, GluN2A, GluN2B and PSD-95) in the hippocampus, prefrontal cortex (PFC) and amygdala were examined. A significant reduction in the sucrose intake induced by CMS was increased by magnesium treatment at a dose of 15 mg/kg, beginning from the third week of administration. Magnesium did not affect this behavioural parameter in the control animals. CMS significantly increased the level of the GluN1 subunit in the amygdala (by 174%) and GluN2A in the hippocampus (by 191%), both of which were significantly attenuated by magnesium treatment. Moreover, magnesium treatment in CMS animals increased the level of GluN2B (by 116%) and PSD-95 (by 150%) in the PFC. The present results for the first time demonstrate the antidepressant-like activity of magnesium in the animal model of anhedonia (CMS), thus indicating the possible involvement of the NMDA/glutamatergic receptors in this activity.

  2. Chronic unpredicted mild stress-induced depression alter saxagliptin pharmacokinetics and CYP450 activity in GK rats

    Directory of Open Access Journals (Sweden)

    Zhengchao Xia

    2016-01-01

    Full Text Available Background. This study was to explore the pharmacokinetics of saxagliptin (Sax in Goto–Kakizaki (GK rats complicated with depression induced by chronic unpredicted mild stress (CUMS. The comorbidity of diabetic patients with depression is becoming more and more epidemic. Whether depression mental disorder alters the pharmacokinetics of hypoglycemic drugs in diabetes patients is not clear.Methods. Five-week-old male GK rats were kept in the cage for 7 weeks in a specific pathogen free (SPF-grade lab until the emergence of diabetes and were then divided into two groups: control group and depression model group. Rats in the CUMS-induced depression group were exposed to a series of stressors for 8 weeks. Plasma serotonin and dopamine levels and behavior of open-field test were used to confirm the establishment of the depression model. All rats were given 0.5 mg/kg Sax orally after 8 weeks and blood samples were collected at different time points. The Sax concentration was assayed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS. The CYP450 activity of the liver microsomes was determined by using cocktails of probe drugs in which the activities of CYP enzymes were assessed through the determination of the production of the probe drugs.Results. Statistically significant differences in Sax pharmacokinetics were observed for area under curve, clearance, peak concentration, peak time and mean residence time between the depression rats and the control rats, while no statistical differences were observed for half-time and distribution volume by HPLC-MS/MS analysis. The CYP450 activity had different changes in the depression group.Conclusions. These results indicated that CUMS-induced depression alters the drug metabolic process of Sax and CYP450 activity of the liver microsomal enzymes in GK rats.

  3. Sex-dependent influence of chronic mild stress (CMS) on voluntary alcohol consumption; study of neurobiological consequences.

    Science.gov (United States)

    Marco, Eva M; Ballesta, Javier Antonio; Irala, Carlos; Hernández, María-Donina; Serrano, María Elisa; Mela, Virginia; López-Gallardo, Meritxell; Viveros, María-Paz

    2017-01-01

    Alcohol use disorder and depression are highly comorbid, and both conditions exhibit important sexual dimorphisms. Here, we aimed to investigate voluntary alcohol consumption after 6weeks of chronic mild stress (CMS) in Wistar rats - employed as an animal model of depression. Male and female rats were investigated, and changes in several molecular markers were analysed in frontal cortex (FCx) and hippocampal formation (HF). CMS induced depressive-like responses in the forced swimming test - increased immobility time - in male and female animals, without affecting anhedonia (sucrose preference test) nor motor activity (holeboard); body weight gain and food intake were diminished only among CMS males. Voluntary alcohol consumption was evaluated in a two-bottle choice paradigm (ethanol 20% versus tap water) for 4 consecutive days; females exhibited a higher preference for alcohol compared to male animals. In particular, alcohol consumption was significantly higher among CMS females compared to CMS male animals. Remarkably, similar changes in both male and female animals exposed to CMS were observed regarding the expression levels of NCAM-140KDa (decrease), GFAP and CB1R expression (increase) within the FCx as well as for HF PSD-95 levels (increase). However, contrasting effects in males and females were reported in relation to synaptophysin (SYN) protein levels within the FCx, HF CB1R expression (a decrease among male animals but an increase in females); while the opposite pattern was observed for NCAM-140KDa protein levels in the HF. A decrease in CB2R expression was only observed in the HF of CMS-females. The present study suggests that male and female animals might be differentially affected by CMS regarding later voluntary alcohol consumption. In this initial approach, cortical SYN, and NCAM-140KDa, CB1R and CB2R expression within the HF have arisen as potential candidates to explain such sex differences in behaviour. However, the depression

  4. The effects of reboxetine treatment on depression-like behavior, brain neurotrophins, and ERK expression in rats exposed to chronic mild stress.

    Science.gov (United States)

    First, Maya; Gil-Ad, Irit; Taler, Michal; Tarasenko, Igor; Novak, Nurit; Weizman, Abraham

    2013-05-01

    Chronic mild stress (CMS) in rats is an established rodent depression model. Antidepressants attenuate the depression-like symptoms and prevent the biochemical changes caused by stress. In the present study, we examined the effect of CMS and the selective norepinephrine reuptake inhibitor (NRI) reboxetine (REB) treatment on behavioral parameters in rats and on hippocampal and cortical neurotrophic factors. Male Sprague Dawley rats were exposed for 5 weeks to a variety of mild stressors. REB (5 mg/kg/i.p.) was daily injected to half of the stressed and unstressed groups. Animal behavior following CMS was tested using the Morris Water Maze (MWM) cognitive paradigm and by monitoring sucrose intake and weight gain. After 5 weeks of CMS, stressed rats showed decreased sucrose intake, and REB treatment normalized this decrease. CMS reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, and REB treatment reversed this alteration and increased BDNF receptor (TrkB) levels. REB elevated hippocampal extracellular signal-regulated kinase (ERK) phosphorylation of both stressed and unstressed rats. In conclusion, our study shows that BDNF, its receptor TrkB, and ERK participate in the neurobiological response to chronic stress and in the molecular and cellular activities of REB in the hippocampus.

  5. Neuroplastic Correlates in the mPFC Underlying the Impairment of Stress-Coping Ability and Cognitive Flexibility in Adult Rats Exposed to Chronic Mild Stress during Adolescence

    Science.gov (United States)

    Zhang, Yu; Shao, Feng; Wang, Qiong; Xie, Xi

    2017-01-01

    Using a valid chronic mild stress (CMS) model of depression, we found that adolescent (postnatal days [PND] 28–41) CMS induced transient alterations in anhedonia that did not persist into adulthood after a 3-week recovery period. Previously stressed adult rats exhibited more immobility/despair behaviors in the forced swimming test and a greater number of trials to reach criterion in the set-shifting task, suggesting the impaired ability to cope with stressors and the cognitive flexibility that allows adaptation to dynamic environments during adulthood. In addition, adult rat exposure to adolescent CMS had a relatively inhibited activation in ERK signaling and downstream protein expression of phosphorylated cAMP-response element-binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in the medial prefrontal cortex. Further correlation analysis demonstrated that immobility and set-shifting performance were positively correlated with the inhibition of ERK signaling. These results indicated adolescent CMS can be used as an effective stressor to model an increased predisposition to adult depression. PMID:28182105

  6. Differential proteomic analysis of the anti-depressive effects of oleamide in a rat chronic mild stress model of depression.

    Science.gov (United States)

    Ge, Lin; Zhu, Ming-Ming; Yang, Jing-Yu; Wang, Fang; Zhang, Rong; Zhang, Jing-Hai; Shen, Jing; Tian, Hui-Fang; Wu, Chun-Fu

    2015-04-01

    Depression is a complex psychiatric disorder, and its etiology and pathophysiology are not completely understood. Depression involves changes in many biogenic amine, neuropeptide, and oxidative systems, as well as alterations in neuroendocrine function and immune-inflammatory pathways. Oleamide is a fatty amide which exhibits pharmacological effects leading to hypnosis, sedation, and anti-anxiety effects. In the present study, the chronic mild stress (CMS) model was used to investigate the antidepressant-like activity of oleamide. Rats were exposed to 10weeks of CMS or control conditions and were then subsequently treated with 2weeks of daily oleamide (5mg/kg, i.p.), fluoxetine (10mg/kg, i.p.), or vehicle. Protein extracts from the hippocampus were then collected, and hippocampal maps were generated by way of two-dimensional gel electrophoresis (2-DE). Altered proteins induced by CMS and oleamide were identified through mass spectrometry and database searches. Compared to the control group, the CMS rats exhibited significantly less body weight gain and decreased sucrose consumption. Treatment with oleamide caused a reversal of the CMS-induced deficit in sucrose consumption. In the proteomic analysis, 12 protein spots were selected and identified. CMS increased the levels of adenylate kinase isoenzyme 1 (AK1), nucleoside diphosphate kinase B (NDKB), histidine triad nucleotide-binding protein 1 (HINT1), acyl-protein thioesterase 2 (APT-2), and glutathione S-transferase A4 (GSTA4). Compared to the CMS samples, seven spots changed significantly following treatment with oleamide, including GSTA4, glutathione S-transferase A6 (GSTA6), GTP-binding nuclear protein Ran (Ran-GTP), ATP synthase subunit d, transgelin-3, small ubiquitin-related modifier 2 (SUMO2), and eukaryotic translation initiation factor 5A-1 (eIF5A1). Of these seven proteins, the level of eIF5A1 was up-regulated, whereas the remaining proteins were down-regulated. In conclusion, oleamide has antidepressant

  7. 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

    used in situ hybridization to elucidate the molecular mechanisms, which may be involved in the development of anhedonia during CMS. In the CA3 of the ventral hippocampus, we found upregulation of brain-derived neurotrophic factor (BDNF) mRNA in the CMS resilient group indicating protective role of BDNF...... to CMS and found the latter to be more valid as rats probably easier adapt to restraint stress. Finally, we used the conditioned place preference model to demonstrate a clear tendency towards a distinct morphine induced behavioral difference between CMS resilient and CMS sensitive animals. Udgivelsesdato...

  8. Assessing the Impact of Post Traumatic Stress Symptoms on Resting State Function Networks in a Military Chronic Mild Traumatic Brain Injury Sample.

    Science.gov (United States)

    Nathan, Dominic E; Bellgowan, Julie F; French, Louis M; Wolf, Jonathan P; Oakes, Terry; Mielke, Jeannine B; Sham, Elyssa B; Liu, Wei; Riedy, Gerard

    2017-03-19

    The relationship between post traumatic stress disorder (PTSD) and chronic symptoms of mild traumatic brain injury (mTBI) is difficult to discern and poorly understood. An accurate differential diagnosis, assessment and treatment of mTBI and PTSD is challenging due to significant symptom overlap and the absence of clearly established biomarkers. The objective of this work is to examine how post traumatic stress influences task-free brain networks in chronic mTBI subjects. Control subjects (N=44) were compared with chronic mTBI subjects with low (N=58, PCLC totalpost traumatic stress symptoms (PTSS). The results indicate significant differences in Brodmann area 10 for all mTBI subject groups, indicating potential mTBI related disruptions with regulation of emotions and decision-making. The effects of PTSS were observed in the anterior cingulate, and parahippocampus suggesting possible disruptions pertaining to memory regulation, encoding and retrieval. The overall results indicate the presence of aberrant connectivity patterns between controls and chronic mTBI subjects with low, medium and high PTSS. Furthermore, the findings suggest a disruption in attention relating to a network of brain regions involved with emotional regulation and memory coding, rather than a fear related response. Taken together, the results suggest these regions form a network that could be a target for future research pertaining to PTSD and chronic mTBI. Furthermore, the use of clinical measures, task based imaging studies or multimodal imaging could help further elucidate specific neural correlates of PTSS and mTBI.

  9. Diffusion kurtosis imaging and high-resolution MRI demonstrate structural aberrations of caudate putamen and amygdala after chronic mild stress.

    Science.gov (United States)

    Delgado y Palacios, Rafael; Verhoye, Marleen; Henningsen, Kim; Wiborg, Ove; Van der Linden, Annemie

    2014-01-01

    The pathophysiology of major depressive disorder (MDD) and other stress related disorders has been associated with aberrations in the hippocampus and the frontal brain areas. More recently, other brain regions, such as the caudate nucleus, the putamen and the amygdala have also been suggested to play a role in the development of mood disorders. By exposing rats to a variety of stressors over a period of eight weeks, different phenotypes, i.e. stress susceptible (anhedonic-like) and stress resilient animals, can be discriminated based on the sucrose consumption test. The anhedonic-like animals are a well validated model for MDD. Previously, we reported that in vivo diffusion kurtosis imaging (DKI) of the hippocampus shows altered diffusion properties in chronically stressed rats independent of the hedonic state and that the shape of the right hippocampus is differing among the three groups, including unchallenged controls. In this study we evaluated diffusion properties in the prefrontal cortex, caudate putamen (CPu) and amygdala of anhedonic-like and resilient phenotypes and found that mean kurtosis in the CPu was significantly different between the anhedonic-like and resilient animals. In addition, axial diffusion and radial diffusion were increased in the stressed animal groups in the CPu and the amygdala, respectively. Furthermore, we found that the CPu/brain volume ratio was increased significantly in anhedonic-like animals as compared with control animals. Concurrently, our results indicate that the effects of chronic stress on the brain are not lateralized in these regions. These findings confirm the involvement of the CPu and the amygdala in stress related disorders and MDD. Additionally, we also show that DKI is a potentially important tool to promote the objective assessment of psychiatric disorders.

  10. 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.

  11. Mild mental stress in diabetes

    DEFF Research Database (Denmark)

    Hildebrandt, P; Mehlsen, J; Sestoft, L;

    1985-01-01

    A TV-game of tennis of 20 min duration was used to study the influence of mild mental stress on subcutaneous blood-flow (SBF), blood-pressure and heart rate in nine insulin-dependent diabetics and nine healthy subjects. SBF was measured on the thigh by local clearance of xenon-133. Measurements......--increase in blood-pressure was observed in both groups. In conclusion, we found that even mild mental strain influences SBF in both normal subjects and in diabetics. The induced alterations in the two groups are different, probably because of a slight parasympathetic dysfunction in the diabetics....

  12. Chronic ultra-mild stress improves locomotor performance of B6D2F1 mice in a motor risk situation.

    Science.gov (United States)

    Negroni, Julia; Venault, Patrice; Pardon, Marie Christine; Pérez-Diaz, Fernando; Chapouthier, Georges; Cohen-Salmon, Charles

    2004-12-06

    Chronic low grade stress predispose to psychopathological disorders. We consistently showed that chronic ultra-mild stress (CUMS) applied to B6D2F1 female mice induced behavioral disinhibition in several conflict exploration models. Insufficient reactivity to conflicts may be maladaptive and lead to inappropriate appreciation of potential risks and impaired ability to cope with those. Therefore, the purpose of the study was to assess the effect of a CUMS procedure on the behavior of mice in a motor risk situation based on multisensory conflict. Following three weeks exposure to various mild stressors, stressed and control B6D2F1 mice were tested on the rotating beam to determine how CUMS exposure affected balance control, posture stability and locomotor performance in response to a sensory-motor challenge. Detailed behavioral analysis included several parameters, both postural (height of the trunk, tail angle, number of imbalances, falls and head movements) and kinetic (mean velocity on the beam, distance covered with large and small movements, plus time spent in no-motion episodes). Comparisons between control and stressed mice showed that CUMS exposure increased mean velocity and improved locomotor performance in the learning task. In addition, sensitivity to sensory conflict seemed to be reduced in stressed mice, which displayed fewer behavioral adjustments to the increasing difficulty of the test compared to control mice. The results are discussed in terms of the possible influence of disturbances in behavioral and attentional inhibitory processes following CUMS exposure. Whether longer periods of CUMS exposure would shift the performance on the RTB from improvement to deterioration remain to be established.

  13. TNF-alpha inhibition prevents cognitive decline and maintains hippocampal BDNF levels in the unpredictable chronic mild stress rat model of depression.

    Science.gov (United States)

    Şahin, Tuğçe Demirtaş; Karson, Ayşe; Balcı, Fuat; Yazır, Yusufhan; Bayramgürler, Dilek; Utkan, Tijen

    2015-10-01

    Previous findings have shown that patients with depression express higher levels of proinflammatory cytokines such as TNF-α and IL-6. We have recently found that Infliximab (a TNF-α inhibitor) decreased anhedonia and despair-like behavior in the rat unpredictable chronic mild stress (UCMS) model of depression suggesting that inflammation might play an important role in depression. An increasing number of studies suggest that inflammation is also associated with cognitive impairments. The current study aimed to investigate the effect of UCMS on the cognitive performance of rats and their hippocampal BDNF levels and the effect of chronic Infliximab (5mg/kg/weekly, i.p.) treatment on these measures. Rats were subjected to different types of stressors daily for a period of 56 days to induce depression-like state. The UCMS resulted in impairments in spatial and emotional memory acquisition and retention with no effect on the level of locomotor activity. These behavioral effects of UCMS were accompanied by reduction in the level of BDNF in the CA1 and CA3 regions of the hippocampus. Chronic Infliximab treatment prevented the UCMS-induced cognitive impairments as well as the reduction in the levels of hippocampal brain-derived neurotrophic factor (BDNF). These results suggest that Infliximab improves the spatial and emotional memory impairments induced by chronic stress in rats likely through its effects on hippocampal function by modulating inflammation.

  14. Sex differences in the rapid and the sustained antidepressant-like effects of ketamine in stress-naïve and "depressed" mice exposed to chronic mild stress.

    Science.gov (United States)

    Franceschelli, A; Sens, J; Herchick, S; Thelen, C; Pitychoutis, P M

    2015-04-02

    During the past decade, one of the most striking discoveries in the treatment of major depression was the clinical finding that a single infusion of a sub-anesthetic dose of the N-methyl-d-aspartate receptor antagonist ketamine produces a rapid (i.e. within a few hours) and long-lasting (i.e. up to two weeks) antidepressant effect in both treatment-resistant depressed patients and in animal models of depression. Notably, converging clinical and preclinical evidence support that responsiveness to antidepressant drugs is sex-differentiated. Strikingly, research regarding the antidepressant-like effects of ketamine has focused almost exclusively on the male sex. Herein we report that female C57BL/6J stress-naïve mice are more sensitive to the rapid and the sustained antidepressant-like effects of ketamine in the forced swim test (FST). In particular, female mice responded to lower doses of ketamine (i.e. 3mg/kg at 30 min and 5mg/kg at 24h post-injection), doses that were not effective in their male counterparts. Moreover, tissue levels of the excitatory amino acids glutamate and aspartate, as well as serotonergic activity, were affected in a sex-dependent manner in the prefrontal cortex and the hippocampus, at the same time-points. Most importantly, a single injection of ketamine (10mg/kg) induced sex-dependent behavioral effects in mice subjected to the chronic mild stress (CMS) model of depression. Intriguingly, female mice were more reactive to the earlier effects of ketamine, as assessed in the open field and the FST (at 30 min and 24h post-treatment, respectively) but the antidepressant potential of the drug proved to be longer lasting in males, as assessed in the splash test and the FST (days 5 and 7 post-treatment, respectively). Taken together, present data revealed that ketamine treatment induces sex-dependent rapid and sustained neurochemical and behavioral antidepressant-like effects in stress-naïve and CMS-exposed C57BL/6J mice.

  15. Effects of Ning Shen Ling Granule(宁神灵冲剂)and Dehydroepiandrosterone on Cognitive Function in Mice Undergoing Chronic Mild Stress

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xiao; DONG Yi-long; YANG Nan; LIU Yan-yong; GAO Rui-feng; ZUO Ping-ping

    2007-01-01

    Objective:To investigate the changes of spontaneous and cognitive behavior,and cholinergic M receptors in the brain of mice subjected to chronic mild stress (CMS),and to determine the effect of Ning Shen Ling Granule (宁神灵冲剂,NSL) and dehydroepiandrosterone (DHEA) on them.Methods:CMS model mice were established by applying stress every day for 3 consecutive weeks with 7 kinds of unforeseeable stress sources,and they were medicated for 1 week beginning at the 3rd week of modeling.The changes in behavior were determined by Morris Water Maze and spontaneous movement test,and M-receptor binding activity in cerebral cortex,hippocampus and hypothalamus were measured by radioactive ligand assay with 3H-QNB.Results:(1)The spontaneous movement in CMS model mice was significantly reduced,with the latency for searching platform in Morris Water Maze obviously prolonged (P<0.01),and these abnormal changes in behavior were improved in those treated with NSL and DHEA.(2)The binding ability of M-receptor in cerebral cortex and hippocampus of CMS mice was significantly decreased as compared with those in the control group (P<0.05),but could be restored to the normal level after intervention with NSL or DHEA.Conclusion:The decline of spontaneous movement and spatial learning and memory ability could be induced in animals by chronic mild stress,and that may be related to the low activity of central cholinergic M-receptors.Both NSL and DHEA could effectively alleviate the above-mentioned changes.

  16. Anxiolytic profile of fluoxetine as monitored following repeated administration in animal rat model of chronic mild stress

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    Muhammad Farhan

    2016-09-01

    Full Text Available Background: Fluoxetine, a selective serotonin re-uptake inhibitor (SSRI, has been proposed to be more effective as an antidepressive drug as compared to other SSRIs. After chronic SSRI administration, the increase in synaptic levels of 5-HT leads to desensitization of somatodentritic 5-HT autoreceptors in the raphe nuclei. Chronic stress may alter behavioral, neurochemical and physiological responses to drug challenges and novel stressors. Methods: Twenty four male rats were used in this study. Animals of CMS group were exposed to CMS. Animals of stressed and unstressed group were administrated with fluoxetine at dose of 1.0 mg/kg s well as 5.0 mg/kg repeatedly for 07 days 1 h before exposed to CMS. The objective of the present study was to evaluate that repeated treatment with fluoxetine could attenuate CMS-induced behavioral deficits. Results: Treatment with fluoxetine attenuated CMS-induced behavioral deficits. Fluoxetine administration induced hypophagia in unstressed as well as CMS rats. Acute and repeated administration of fluoxetine increased motor activity in familiar environment but only repeated administration increased exploratory activity in open field. Anxiolytic effects of fluoxetine were greater in unstressed rats. These anxiolytic effects were produced as result of repeated administration not on acute administration of fluoxetine at 1.0 mg/kg as well as 5.0 mg/kg. Conclusion: The present study demonstrated that CMS exposure resulted into behavioral deficits and produced depressive-like symptoms. Fluoxetine, an SSRI, administration attenuated behavioral deficits induced by CMS. Anxiolytic effects of repeated fluoxetine administration were greater in unstressed than CMS animals.

  17. Metabonomic Evaluation of Chronic Unpredictable Mild Stress-Induced Changes in Rats by Intervention of Fluoxetine by HILIC-UHPLC/MS.

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    Longshan Zhao

    Full Text Available Hydrophilic interaction-ultra high performance liquid chromatography (HILIC-UHPLC allows the analysis of highly polar metabolites, providing complementary information to reversed-phase (RP chromatography. By optimization of the preparation and analytical conditions in HILIC mode, HILIC-UHPLC/MS was applied for the global metabolic profiling of rat plasma samples generated in an experimental model of chronic unpredictable mild stress (CUMS, and the concomitant investigation of the protective effect of fluoxetine was also evaluated. Identification of plasma metabolic profiles indicated that significant changes in specific metabolites occurred after fluoxetine exposure, including increased phenylalanine, serine, acetyl-L-carnitine, carnitine and decreased creatine, betaine, proline, tryptophan, tyrosine, C16:0 LPC. Some novel biomarkers from this HILIC-UHPLC/MS approach were betaine, proline, tyrosine creatine and serine compared with the results of RP-UHPLC/MS. The complementary nature of this technique is confirmed and is on agreement with previously published studies.

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

    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.

  19. Proteomic investigation of the ventral rat hippocampus links DRP-2 to escitalopram treatment resistance and SNAP to stress resilience in the chronic mild stress model of depression

    DEFF Research Database (Denmark)

    Bisgaard, Christina; Jayatissa, Magdalena N; Enghild, Jan J

    2007-01-01

    of depression, by exposing rats to a series of mild stressors for 7 weeks, with antidepressant treatment during the last 4 weeks. In the CMS model, animals were split into six different groups at the end of treatment; unchallenged control escitalopram (n = 12), unchallenged control vehicle (n = 12), CMS vehicle...... (n = 12), CMS escitalopram responders (n = 11), CMS escitalopram non-responders (n = 13) and CMS resilient (stress resistant) (n = 12). Protein levels in the ventral rat hippocampus were compared between the groups to provide putative markers of anhedonia, escitalopram resistance, and stress...... resilience. Twenty-eight candidate protein spots were selected, of which 13 were successfully identified using tandem mass spectrometry. DRP-2 (dihydropyrimidinase-related protein-2) was a potential marker for escitalopram resistance, whereas alpha-SNAP and beta-SNAP were associated with stress resilience...

  20. Antidepressant like effects of hydrolysable tannins of Terminalia catappa leaf extract via modulation of hippocampal plasticity and regulation of monoamine neurotransmitters subjected to chronic mild stress (CMS).

    Science.gov (United States)

    Chandrasekhar, Y; Ramya, E M; Navya, K; Phani Kumar, G; Anilakumar, K R

    2017-02-01

    Terminalia catappa L. belonging to Combretaceae family is a folk medicine, known for its multiple pharmacological properties, but the neuro-modulatory effect of TC against chronic mild stress was seldom explored. The present study was designed to elucidate potential antidepressant-like effect of Terminalia cattapa (leaf) hydro-alcoholic extract (TC) by using CMS model for a period of 7 weeks. Identification of hydrolysable tannins was done by using LC-MS. After the CMS exposure, mice groups were administered with imipramine (IMP, 10mg/kg, i.p.) and TC (25, 50 and 100mg/kg of TC, p.o.). Behavioural paradigms used for the study included forced swimming test (FST), tail suspension test (TST) and sucrose preference test (SPT). After behavioural tests, monoamine neurotransmitter, cortisol, AchE, oxidative stress levels and mRNA expression studies relevant to depression were assessed. TC supplementation significantly reversed CMS induced immobility time in FST and other behavioural paradigms. Moreover, TC administration significantly restored CMS induced changes in concentrations of hippocampal neurotransmitters (5-HT, DA and NE) as well as levels of acetyl cholinesterase, cortisol, monoamine oxidases (MAO-A, MAO-B), BDNF, CREB, and p-CREB. It suggests that TC supplementation could supress stress induced depression by regulating monoamine neurotransmitters, CREB, BDNF, cortisol, AchE level as well as by amelioration of oxidative stress. Hence TC can be used as a complementary medicine against depression-like disorder.

  1. 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.

  2. Antidepressant-like action of AGN 2979, a tryptophan hydroxylase activation inhibitor, in a chronic mild stress model of depression in rats.

    Science.gov (United States)

    Gittos, M W; Papp, M

    2001-10-01

    Chronic mild stress (CMS) procedure was used to study an antidepressant-like activity of AGN 2979, a selective inhibitor of tryptophan hydroxylase (TH) activation. At the dose of 4 mg/kg, AGN 2979 fully reversed the CMS-induced reduction in the consumption of 1% sucrose solution. This effect was maintained for at least 1 week after cessation of treatment and no signs of withdrawal were observed in either stressed or control animals receiving AGN 2979. The lower (1 mg/kg) and higher (16 mg/kg) doses were ineffective. The magnitude of action of AGN 2979 in the CMS model was comparable to that of imipramine (10 mg/kg) but its onset of action appears to be faster since the inhibition of sucrose intake in stressed animals was already reversed after the 1st week of AGN 2979 administration while imipramine required 3 weeks of treatment to cause similar effect. These results provide support for the hypothesis that inhibition of TH activation may result in a potent antidepressant activity.

  3. Young-Adult Male Rats' Vulnerability to Chronic Mild Stress Is Reflected by Anxious-Like instead of Depressive-Like Behaviors

    Science.gov (United States)

    José Jaime, Herrera-Pérez; Venus, Benítez-Coronel; Graciela, Jiménez-Rubio; Tania, Hernández-Hernández Olivia

    2016-01-01

    In a previous study, we found that chronic mild stress (CMS) paradigm did not induce anhedonia in young-adult male rats but it reduced their body weight gain. These contrasting results encouraged us to explore other indicators of animal's vulnerability to stress such as anxious-like behaviors, since stress is an etiologic factor also for anxiety. Thus, in this study, we evaluated the vulnerability of these animals to CMS using behavioral tests of depression or anxiety and measuring serum corticosterone. Male Wistar rats were exposed to four weeks of CMS; the animals' body weight and sucrose preference (indicator of anhedonia) were assessed after three weeks, and, after the fourth week, some animals were evaluated in a behavioral battery (elevated plus maze, defensive burying behavior, and forced swimming tests); meanwhile, others were used to measure serum corticosterone. We found that CMS (1) did not affect sucrose preference, immobility behavior in the forced swimming test, or serum corticosterone; (2) decreased body weight gain; and (3) increased the rat's entries into closed arms of the plus maze and the cumulative burying behavior. These data indicate that young male rats' vulnerability to CMS is reflected as poor body weight gain and anxious-like instead of depressive-like behaviors. PMID:27433469

  4. Apigenin ameliorates chronic mild stress-induced depressive behavior by inhibiting interleukin-1β production and NLRP3 inflammasome activation in the rat brain.

    Science.gov (United States)

    Li, Ruipeng; Wang, Xiangxiang; Qin, Tingting; Qu, Rong; Ma, Shiping

    2016-01-01

    Increasing evidence suggests that inflammation and oxidative stress may contribute to the development of major depressive disorder (MDD). Apigenin, a type of bioflavonoid widely found in citrus fruits, has a number of biological actions including anti-inflammatory and antioxidant effects. Although apigenin has potential antidepressant activity, the mechanisms of this effect remain unclear. The present study aims to investigate the effects of apigenin on behavioral changes and inflammatory responses induced by chronic unpredictable mild stress (CUMS) in rats. GW9662, a selective peroxisome proliferator-activated receptor gamma (PPARγ) inhibitor, was administered 30 min before apigenin. We found that treatment with apigenin (20mg/kg, intragastrically) for three weeks remarkably ameliorated CUMS-induced behavioral abnormalities, such as decreased locomotor activity and reduced sucrose consumption. In response to oxidative stress, the NLRP3 inflammasome was activated and IL-1β secretion increased in the prefrontal cortex (PFC) of CUMS rats. However, apigenin treatment upregulated PPARγ expression and downregulated the expression of NLRP3, which subsequently downregulated the production of IL-1β. In addition, GW9662 diminished the inhibitory effects of apigenin on the NLRP3 inflammasome. In conclusion, our results demonstrate that apigenin exhibits antidepressant-like effects in CUMS rats, possibly by inhibiting IL-1β production and NLRP3 inflammasome expression via the up-regulation of PPARγ expression.

  5. Effects of Chronic Mild Stress on the Development of Atherosclerosis and Expression of Toll-Like Receptor 4 Signaling Pathway in Adolescent Apolipoprotein E Knockout Mice

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    Hongfeng Gu

    2009-01-01

    Full Text Available Here, we investigated the effect of chronic mild stress (CMS on the development of atherosclerosis as well as the expression of Toll-like receptors (TLRs signaling pathway in adolescent apolipoprotein E knockout (apoE-/- mice. Mice were subjected to daily CMS for 0, 4, and 12 weeks, respectively. To identify the expression of Toll-like receptor 4 signaling pathway in adolescent apolipoprotein E knockout mice subjected to CMS, we compared gene expression in aortas of stressed and unstressed mice using TLRs signaling pathway real-time PCR microarrays consisting of 87 genes. We found that atherosclerosis lesions both in aortic tress and sinuses of CMS mice were significantly increased linearly in response to duration of CMS exposure. Among 87 genes analyzed, 15 genes were upregulated in stressed mice, especially TLR4, myeloid differentiation factor 88 (MyD88, and IL-1β, and 28 genes were downregulated compared with nonstressed mice. CMS mice demonstrated markedly increased aortic atherosclerosis that were associated with significant increases in levels of expression of TLR4, MyD88, nuclear factor κB (NF-κB, MCP-1, IL-1β, TNF-α, and sICAM-1. Taken together, our results suggest an important role for TLR4 signaling pathway in atherosclerosis in a CMS mouse model.

  6. 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.

  7. Vascular dysfunction in Chronic Mild Stress (CMS) induced depression model in rats: monoamine homeostasis and endothelial dysfunction

    DEFF Research Database (Denmark)

    Bouzinova, Elena; Wiborg, Ove; Aalkjær, Christian;

    Major depression and cardiovascular diseases have strong co-morbidity but the reason for this is unknown. In CMS model of depression only some rats develop depression-like symptoms (i.e. anhedonia, measured by sucrose intake) while others are resilient to 8 weeks of CMS. Anhedonic rats have...... decreased cardiac output and unchanged blood pressure, suggesting increased total peripheral resistance. Small mesenteric and femoral arteries from CMS and non-stressed rats responded similarly to noradrenaline (NA) under control conditions but inhibition of neuronal reuptake with cocaine increased NA...... sensitivity stronger in anhedonic than in resilient and non-stressed groups. In contrast, corticosterone-sensitive extra-neuronal monoamine uptake was diminished in rats exposed to CMS. These changes in monoamine homeostasis were associated with upregulation neuronal NA transporter and reduced expression...

  8. Umbelliferone reverses depression-like behavior in chronic unpredictable mild stress-induced rats by attenuating neuronal apoptosis via regulating ROCK/Akt pathway.

    Science.gov (United States)

    Qin, Tingting; Fang, Fang; Song, Meiting; Li, Ruipeng; Ma, Zhanqiang; Ma, Shiping

    2017-01-15

    There is increasing evidence that major depressive disorder (MDD) is also a progressive neurodegeneration disorder and neuronal damage is the major pathology of MDD. Umbelliferone, a coumarin derivative, was found in a range of plants with proved anti-oxidative, anti-inflammatory and neuroprotective effects. The primary purpose of this investigation was to evaluate whether umbelliferone could confer an antidepressant-like effect on the depressive model in rats developed by chronic unpredictable mild stress (CUMS) and explore the possible mechanism involved in its neuroprotective effects. We found that treatments with umbelliferone (15mg/kg, 30mg/kg) significantly ameliorated CUMS-induced depressive-like behaviors, such as decreased sucrose consumption, reduced locomotor activity and prolonged immobility time. Rats under CUMS stimulation treated with umbelliferone (15mg/kg, 30mg/kg) showed reduced neuronal apoptosis, as well as inhibited inflammatory cytokines levels by down-regulating Rho-associated protein kinase (ROCK) signaling and up-regulating protein kinase B (Akt) signaling. In conclusion, umbelliferone showed neuroprotective effects on CUMS-induced model of depression, which was associated with the inhibition of neuronal apoptosis modulated by ROCK/Akt pathway.

  9. Neuronal apoptosis and synaptic density in the dentate gyrus of ischemic rats' response to chronic mild stress and the effects of Notch signaling.

    Directory of Open Access Journals (Sweden)

    Shaohua Wang

    Full Text Available Our previous research highlighted an inconsistency with Notch1 signaling-related compensatory neurogenesis after chronic mild stress (CMS in rodents suffering from cerebral ischemia, which continue to display post-stroke depressive symptoms. Here, we hypothesize that CMS aggrandized ischemia-related apoptosis injury and worsened synaptic integrity via gamma secretase-meditated Notch1 signaling. Adult rats were exposed to a CMS paradigm after left middle cerebral artery occlusion (MCAO. Open-field and sucrose consumption testing were employed to assess depression-like behavior. Gene expression of pro-apoptotic Bax, anti-apoptotic Bcl-2, and synaptic density-related synaptophysin were measured by western blotting and real-time PCR on Day 28 after MCAO surgery. CMS induced depressive behaviors in ischemic rats, which was accompanied by an elevation in Bax/bcl-2 ratio, TUNEL staining in neurons and reduced synaptophysin expression in the dentate gyrus. These collective effects were reversed by the gamma-secretase inhibitor DAPT (N-[N-(3,5-difluorophenacetyl-L-alanyl]-S-phenyl-glycine t-butyl ester. We found that post-stroke stressors made neurons in the dentate gyrus vulnerable to apoptosis, which supports a putative role for Notch signaling in neural integrity, potentially in newborn cells' synaptic deficit with regard to preexisting cells. These findings suggest that post-stroke depression therapeutically benefits from blocking gamma secretase mediated Notch signaling, and whether this signaling pathway could be a therapeutic target needs to be further investigated.

  10. 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.

  11. iTRAQ-based quantitative analysis of hippocampal postsynaptic density-associated proteins in a rat chronic mild stress model of depression.

    Science.gov (United States)

    Han, X; Shao, W; Liu, Z; Fan, S; Yu, J; Chen, J; Qiao, R; Zhou, J; Xie, P

    2015-07-09

    Major depressive disorder (MDD) is a prevalent psychiatric mood illness and a major cause of disability and suicide worldwide. However, the underlying pathophysiology of MDD remains poorly understood due to its heterogenic nature. Extensive pre-clinical research suggests that many molecular alterations associated with MDD preferentially localize to the postsynaptic density (PSD). Here, we used a rodent chronic mild stress (CMS) model to generate susceptible and unsusceptible subpopulations. Proteomic analysis using an isobaric tag for relative and absolute quantitation (iTRAQ) and tandem mass spectrometry was performed to identify differentially expressed proteins in enriched PSD preparations from the hippocampi of different groups. More than 1500 proteins were identified and quantified, and 74 membrane proteins were differentially expressed. Of these membrane proteins, 51 (69%) were identified by SynaptomeDB search as having a predicted PSD localization. The unbiased profiles identified several PSD candidate proteins that may be related to CMS vulnerability or insusceptibility, and these two CMS phenotypes displayed differences in the abundance of several types of proteins. A detailed protein functional analysis pointed to a role for PSD-associated proteins involved in signaling and regulatory functions. Within the PSD, the N-methyl-D-aspartate (NMDA) receptor subunit NR2A and its downstream targets contribute to CMS susceptibility. Further analysis of disease relevance indicated that the PSD contains a complex set of proteins of known relevance to mental illnesses including depression. In sum, these findings provide novel insights into the contribution of PSD-associated proteins to stress susceptibility and further advance our understanding of the role of hippocampal synaptic plasticity in MDD.

  12. Influences of Chronic Mild Stress Exposure on Motor, Non-Motor Impairments and Neurochemical Variables in Specific Brain Areas of MPTP/Probenecid Induced Neurotoxicity in Mice.

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    Udaiyappan Janakiraman

    Full Text Available Parkinson's disease (PD is regarded as a movement disorder mainly affecting the elderly population and occurs due to progressive loss of dopaminergic (DAergic neurons in nigrostriatal pathway. Patients suffer from non-motor symptoms (NMS such as depression, anxiety, fatigue and sleep disorders, which are not well focussed in PD research. Depression in PD is a predominant /complex symptom and its pathology lies exterior to the nigrostriatal system. The main aim of this study is to explore the causative or progressive effect of chronic mild stress (CMS, a paradigm developed as an animal model of depression in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (25 mg/kg. body wt. with probenecid (250 mg/kg, s.c. (MPTP/p induced mice model of PD. After ten i.p. injections (once in 3.5 days for 5 weeks of MPTP/p or exposure to CMS for 4 weeks, the behavioural (motor and non-motor impairments, levels and expressions of dopamine (DA, serotonin (5-HT, DAergic markers such as tyrosine hydroxylase (TH, dopamine transporter (DAT, vesicular monoamine transporters-2 (VMAT 2 and α-synuclein in nigrostriatal (striatum (ST and substantia nigra (SN and extra-nigrostriatal (hippocampus, cortex and cerebellum tissues were analysed. Significantly decreased DA and 5-HT levels, TH, DAT and VMAT 2 expressions and increased motor deficits, anhedonia-like behaviour and α-synuclein expression were found in MPTP/p treated mice. Pre and/or post exposure of CMS to MPTP/p mice further enhanced the MPTP/p induced DA and 5-HT depletion, behaviour abnormalities and protein expressions. Our results could strongly confirm that the exposure of stress after MPTP/p injections worsens the symptoms and neurochemicals status of PD.

  13. 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.

  14. Evidence for oxidative stress in the developing cerebellum of the rat after chronic mild carbon monoxide exposure (0.0025% in air

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    Lopez Ivan A

    2009-05-01

    Full Text Available Abstract Background The present study was designed to test the hypothesis that chronic very mild prenatal carbon monoxide (CO exposure (25 parts per million subverts the normal development of the rat cerebellar cortex. Studies at this chronic low CO exposure over the earliest periods of mammalian development have not been performed to date. Pregnant rats were exposed chronically to CO from gestational day E5 to E20. In the postnatal period, rat pups were grouped as follows: Group A: prenatal exposure to CO only; group B: prenatal exposure to CO then exposed to CO from postnatal day 5 (P5 to P20; group C: postnatal exposure only, from P5 to P20, and group D, controls (air without CO. At P20, immunocytochemical analyses of oxidative stress markers, and structural and functional proteins were assessed in the cerebellar cortex of the four groups. Quantitative real time PCR assays were performed for inducible (iNOS, neuronal (nNOS, and endothelial (eNOS nitric oxide synthases. Results Superoxide dismutase-1 (SOD1, SOD2, and hemeoxygenase-1 (HO-1 immunoreactivity increased in cells of the cerebellar cortex of CO-exposed pups. INOS and nitrotyrosine immunoreactivity also increased in blood vessels and Purkinje cells (PCs of pups from group-A, B and C. By contrast, nNOS immunoreactivity decreased in PCs from group-B. Endothelial NOS immunoreactivity showed no changes in any CO-exposed group. The mRNA levels for iNOS were significantly up-regulated in the cerebellum of rats from group B; however, mRNA levels for nNOS and eNOS remained relatively unchanged in groups A, B and C. Ferritin-H immunoreactivity increased in group-B. Immunocytochemistry for neurofilaments (structural protein, synapsin-1 (functional protein, and glutamic acid decarboxylase (the enzyme responsible for the synthesis of the inhibitory neurotransmitter GABA, were decreased in groups A and B. Immunoreactivity for two calcium binding proteins, parvalbumin and calbindin, remained

  15. 7,8-Dihydroxyflavone, a Tropomyosin-Kinase Related Receptor B Agonist, Produces Fast-Onset Antidepressant-Like Effects in Rats Exposed to Chronic Mild Stress

    Science.gov (United States)

    Chang, Hsin-An; Wang, Ying-Hsiu; Tung, Che-Se; Yeh, Chin-Bin

    2016-01-01

    Objective Brain-derived neurotrophic factor (BDNF) and its specific receptor, tropomyosin-related kinase (TrkB), play important roles in treating depression. In this experiment, we examined whether 7,8-dihydroxyflavone, a novel potent TrkB agonist, could reverse the behavioral and biochemical abnormalities induced by the chronic mild stress (CMS) paradigm in rats. Methods SD rats were exposed to a battery of stressors for 56 days. 7,8-dihydroxyflavone (5 and 20 mg/kg) were administered intraperitoneally during the last 28 days of the CMS paradigm. Rats were tested in sucrose consumption test (SCT), forced-swimming test (FST) and elevated T-maze (ETM). Serum corticosterone levels and hippocampal BDNF levels of the rats were measured. Results Four-week CMS on the rats induced their depression-like behavior in SCT. The CMS-reduced sucrose consumption was reversed starting from 7 days after the 7,8-dihydroxyflavone (20 mg/kg) treatment and remained across the subsequent treatment regime. 7,8-dihydroxyflavone, when given at 5 mg/kg for 3 weeks, reduced the immobility time in the FST in the CMS-subjected rats. Additionally, the 4-week treatment with 7,8-dihydroxyflavone (20 mg/kg) attenuated the CMS-induced increase in anxiety-like behavior in the ETM. For the CMS-subjected rats, 7,8-dihydroxyflavone treatment dose-dependently reduced their serum corticosterone levels but increased their hippocampal BDNF levels only at 5 mg/kg. Conclusion 7,8-dihydroxyflavone was beneficial for both depression and anxiety-like behaviors, and may exert fast-onset antidepressant effects. This provides a new insight into the pharmacological management of depression.

  16. 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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    Isingrini, Elsa; Camus, Vincent; Le Guisquet, Anne-Marie; Pingaud, Maryse; Devers, Séverine; Belzung, Catherine

    2010-01-01

    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. PMID:20436931

  17. 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.

  18. 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

  19. Chronic stress, cognitive functioning and mental health.

    Science.gov (United States)

    Marin, Marie-France; Lord, Catherine; Andrews, Julie; Juster, Robert-Paul; Sindi, Shireen; Arsenault-Lapierre, Geneviève; Fiocco, Alexandra J; Lupien, Sonia J

    2011-11-01

    This review aims to discuss the evidence supporting the link between chronic stress, cognitive function and mental health. Over the years, the associations between these concepts have been investigated in different populations. This review summarizes the findings that have emerged from older populations as well as from populations suffering from pathological aging, namely Mild Cognitive Impairment and Alzheimer's Disease. Although older adults are an interesting population to study in terms of chronic stress, other stress-related diseases can occur throughout the lifespan. The second section covers some of these stress-related diseases that have recently received a great deal of attention, namely burnout, depression, and post-traumatic stress disorder. Given that chronic stress contributes to the development of certain pathologies by accelerating and/or exacerbating pre-existing vulnerabilities that vary from one individual to the other, the final section summarizes data obtained on potential variables contributing to the association between chronic stress and cognition.

  20. Chronic Stress and Performance

    Science.gov (United States)

    2011-09-01

    to the cannabinoid CB(1) receptor agonist HU-210 following chronic stress. European Journal of Pharmacology, 499(3), 291-295. Holscher, C. (1999...learning and memory, has the highest concentration of GC receptors in the brain and is involved in the stress response. Extensive research has... receptor levels than stressed male rodents (Konkle, 2003; Figueiredo, 2002; Handa, 1994). Males and females react to stress differently, so two models

  1. Chronic post-traumatic headache after mild head injury

    DEFF Research Database (Denmark)

    Kjeldgaard, Dorte; Forchhammer, Hysse; Teasdale, Tom

    2014-01-01

    to or above the cut-off score for having post-traumatic stress disorder (PTSD) according to the HTQ. In terms of demographics and headache, the groups were comparable except the CPTH group were more often without affiliation to the labour market ( P ...BACKGROUND: The aetiology behind chronic post-traumatic headache (CPTH) after mild head injury is unclear and management is complicated. In order to optimize treatment strategies we aimed to characterize a CPTH population. METHODS: Ninety patients with CPTH and 45 patients with chronic primary...... headaches were enrolled from the Danish Headache Center. All patients were interviewed about demographic and headache data. They completed the Harvard Trauma Questionnaire (HTQ), Rivermead Post Concussion Symptoms Questionnaire, SF-36 and a headache diary. RESULTS: The CPTH group experienced more cognitive...

  2. 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

  3. 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。

  4. Effects of prenatal chronic mild stress exposure on hippocampal cell proliferation, expression of GSK-3α, β and NR2B in adult offspring during fear extinction in rats.

    Science.gov (United States)

    Li, Min; Li, Xiaobai; Zhang, Xinxin; Ren, Jintao; Jiang, Han; Wang, Yan; Ma, Yuchao; Cheng, Wenwen

    2014-06-01

    Stress during pregnancy has been implicated as a risk factor for the development of many mental disorders; however, the influence of prenatal stress on the fear or anxiety-related behaviors, especially the fear extinction in adult offspring has been little investigated. In order to investigate how prenatal stress affects fear extinction, which is regarded as a form of new learning that counteracts the expression of Pavlovian's conditioned fear, a rat model of prenatal chronic mild stress (PNS) was used to evaluate the effects of PNS on fear extinction in adult offspring. The expression of hippocampal glycogen synthase kinase-3s (GSK-3α, β), N-methyl-d-aspartic acid receptors (NMDARs)-2B and the hippocampal cell proliferation in dentate gyrus in the adult offspring during fear extinction were studied. Our results showed that PNS significantly reduced body weight of pups, indicating PNS might induce growth retardation in offspring. Moreover, PNS significantly enhanced the freezing behavior of offspring at the phase of extinction, suggesting PNS impaired the abilities of fear extinction learning. In addition, PNS significantly increased the levels of GSK-3α, β and NR2B, but reduced hippocampal cell proliferation during fear extinction. Taken together, our findings suggest that maternal stress during pregnancy can impair the fear extinction of adult offspring, probably by affecting the neural plasticity of brain.

  5. 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.

  6. 1,2,3,4-Tetrahydroisoquinoline produces an antidepressant-like effect in the forced swim test and chronic mild stress model of depression in the rat: Neurochemical correlates.

    Science.gov (United States)

    Możdżeń, Edyta; Papp, Mariusz; Gruca, Piotr; Wąsik, Agnieszka; Romańska, Irena; Michaluk, Jerzy; Antkiewicz-Michaluk, Lucyna

    2014-04-15

    1,2,3,4-Tetrahydroisoquinoline (TIQ) is an exo- and endogenous amine naturally present in mammalian brain which displays antidepressant-like effect in various animal models: the forced swim test (FST) and chronic mild stress (CMS) paradigm in rats. To elucidate this action we compared the effects of TIQ with imipramine, a classic antidepressant drug and one of the most clinically effective. Applied behavioral tests showed that TIQ produced an antidepressant-like effect with a potency comparable to that of imipramine. TIQ (25-50mg/kg i.p.), similarly to imipramine (10-30mg/kg i.p.), reduced the immobility time in FST and completely reversed the decrease in sucrose intake caused by CMS in the rat. In addition, in order to avoid the possible psychostimulating effect of TIQ we examined the influence of its administration on locomotor activity in rats. TIQ, like imipramine, produced a reduction in horizontal locomotor activity. This suggested that TIQ did not have psychostimulant properties and that prolonged swimming in the FST was a result of an increased motivation to escape from the stressful situation. The biochemical analyses have shown that TIQ activates monoaminergic systems as a reversible monoamine oxidase (MAO) inhibitor and free radical scavenger. Beyond the activation of noradrenaline and serotonin systems, TIQ also moderately affects the dopamine system. On the basis of the presented behavioral and biochemical studies we suggest that TIQ is a potential new antidepressant which may be effective for the depression therapy in a clinical setting.

  7. The neurogenic effects of an enriched environment and its protection against the behavioral consequences of chronic mild stress persistent after enrichment cessation in six-month-old female Balb/C mice.

    Science.gov (United States)

    Vega-Rivera, Nelly Maritza; Ortiz-López, Leonardo; Gómez-Sánchez, Ariadna; Oikawa-Sala, Julian; Estrada-Camarena, Erika Monserrat; Ramírez-Rodríguez, Gerardo Bernabé

    2016-03-15

    Because stress may underlie the presence of depressive episodes, strategies to produce protection against or to reverse the effects of stress on neuroplasticity and behavior are relevant. Preclinical studies showed that exposure to stimuli, such as physical activity and environmental enrichment (ENR), produce beneficial effects against stress causing antidepressant-like effects in rodents. Additionally, ENR induces positive effects on neuroplasticity, neurochemistry and behavior at any age of rodents tested. Here, we analyzed whether ENR exposure prevents the development of depressive-like behavior produced by unpredictable, chronic mild stress (CMS) exposure as well as changes in hippocampal neurogenesis in a six-month-old female Balb/C mice, strain that shows low baseline levels of hippocampal neurogenesis. Mice were assigned to one of four groups: (1) normal housing-normal housing (NH-NH), (2) NH-CMS, (3) ENR-NH, or (4) ENR-CMS. The animals were exposed over 46 days to ENR or NH and subsequently to NH or CMS for 4 weeks. ENR induces long-term effects protecting against CMS induction of anhedonia and hopelessness behaviors. Independent of housing conditions, ENR increased the number of proliferative cells (Ki67), and CMS decreased the number of proliferative cells. ENR increased the newborn cells (BrdU) and mature phenotypes of neurons; these effects were not changed by CMS exposure. Similarly, the number of doublecortin-positive cells was not affected by CMS in ENR mice, which showed more cells with complex dendrite arborizations. Our study suggests that ENR induces protection against the effects of CMS on behavior and neuroplasticity in six-month-old Balb/C mice.

  8. Effects of pentoxifylline, 7-nitroindazole, and imipramine on tumor necrosis factor-α and indoleamine 2,3-dioxygenase enzyme activity in the hippocampus and frontal cortex of chronic mild-stress-exposed rats

    Directory of Open Access Journals (Sweden)

    Mohamed BMSA

    2013-05-01

    Full Text Available Bassim MSA Mohamed,1,6 Sawsan Aboul-Fotouh,2,5 Eman A Ibrahim,3 Hanan Shehata,4 Amal A Mansour,4 Nemat AZ Yassin,1 Wafaa El-Eraky,1 Ahmed M Abdel-Tawab2,5 1Department of Pharmacology, National Research Centre, Cairo, Egypt; 2Department of Pharmacology, 3Department of Pathology, 4Department of Medical Biochemistry and Molecular Biology, 5Clinical Pharmacology Unit, Ain Shams University, Cairo, Egypt; 6Atlantic Veterinary College, University of Prince Edward Island, Charlottetown, PE, Canada Objectives: This study aimed to investigate the role of tumor necrosis factor (TNF-α and the neuronal nitric oxide synthase enzyme in dysregulation of indoleamine 2,3-dioxygenase (IDO enzyme, and hence serotonin availability in chronic mild stress (CMS, an animal model of depression. Methods: Rats were divided into five groups: two control and CMS-exposed for 6 weeks, and another three groups exposed to CMS and administered pentoxifylline 50 mg/kg/day intraperitoneally, 7-nitroindazole 40 mg/kg/day subcutaneously, or imipramine 20 mg/kg/day intraperitoneally for the previous 3 CMS weeks. Rats were assessed for neurochemical and immunohistochemical abnormalities. Results: Pentoxifylline-, 7-nitroindazole-, and imipramine-treated rats showed amelioration of CMS-induced behavioral deficits that was accompanied by significant reduction in kynurenine/serotonin molar ratio and nitrates/nitrites in frontal cortex and hippocampus. In the pentoxifylline and 7-nitroindazole groups, serum TNF-α was reduced relative to the CMS group (18.54 ± 0.85 and 19.16 ± 1.54 vs 26.20 ± 1.83 pg/mL, respectively; P < 0.05. Exposure to CMS increased TNF-α and IDO immunohistochemical staining scores in both hippocampus and midbrain raphe nuclei. 7-Nitroindazole and pentoxifylline significantly (P < 0.05 reduced TNF-α immunostaining in hippocampus and raphe nuclei, with significant (P < 0.01 reduction of IDO immunostaining in raphe nuclei. Likewise, imipramine reduced TNF

  9. 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.

  10. 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

  11. Acute stress does not affect the impairing effect of chronic stress on memory retrieval

    Directory of Open Access Journals (Sweden)

    Jamile Ozbaki

    2016-07-01

    Full Text Available Objective(s: Due to the prevalence and pervasiveness of stress in modern life and exposure to both chronic and acute stresses, it is not clear whether prior exposure to chronic stress can influence the impairing effects of acute stress on memory retrieval. This issue was tested in this study. Materials and Methods: Adult male Wistar rats were randomly assigned to the following groups: control, acute, chronic, and chronic + acute stress groups. The rats were trained with six trials per day for 6 consecutive days in the water maze. Following training, the rats were either kept in control conditions or exposed to chronic stress in a restrainer 6 hr/day for 21 days. On day 22, a probe test was done to measure memory retention. Time spent in target and opposite areas, platform location latency, and proximity were used as indices of memory retention. To induce acute stress, 30 min before the probe test, animals received a mild footshock. Results: Stressed animals spent significantly less time in the target quadrant and more time in the opposite quadrant than control animals. Moreover, the stressed animals showed significantly increased platform location latency and proximity as compared with control animals. No significant differences were found in these measures among stress exposure groups. Finally, both chronic and acute stress significantly increased corticosterone levels. Conclusion: Our results indicate that both chronic and acute stress impair memory retrieval similarly. Additionally, the impairing effects of chronic stress on memory retrieval were not influenced by acute stress.

  12. 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

  13. Integration of ¹H NMR and UPLC-Q-TOF/MS for a comprehensive urinary metabonomics study on a rat model of depression induced by chronic unpredictable mild stress.

    Directory of Open Access Journals (Sweden)

    Hong-Mei Jia

    Full Text Available Depression is a type of complex psychiatric disorder with long-term, recurrent bouts, and its etiology remains largely unknown. Here, an integrated approach utilizing (1H NMR and UPLC-Q-TOF/MS together was firstly used for a comprehensive urinary metabonomics study on chronic unpredictable mild stress (CUMS treated rats. More than twenty-nine metabolic pathways were disturbed after CUMS treatment and thirty-six potential biomarkers were identified by using two complementary analytical technologies. Among the identified biomarkers, nineteen (10, 11, 16, 17, 21-25, and 27-36 were firstly reported as potential biomarkers of CUMS-induced depression. Obviously, this paper presented a comprehensive map of the metabolic pathways perturbed by CUMS and expanded on the multitude of potential biomarkers that have been previously reported in the CUMS model. Four metabolic pathways, including valine, leucine and isoleucine biosynthesis; phenylalanine, tyrosine and tryptophan biosynthesis; tryptophan metabolism; synthesis and degradation of ketone bodies had the deepest influence in the pathophysiologic process of depression. Fifteen potential biomarkers (1-2, 4-6, 15, 18, 20-23, 27, 32, 35-36 involved in the above four metabolic pathways might become the screening criteria in clinical diagnosis and predict the development of depression. Moreover, the results of Western blot analysis of aromatic L-amino acid decarboxylase (DDC and indoleamine 2, 3-dioxygenase (IDO in the hippocampus of CUMS-treated rats indicated that depletion of 5-HT and tryptophan, production of 5-MT and altered expression of DDC and IDO together played a key role in the initiation and progression of depression. In addition, none of the potential biomarkers were detected by NMR and LC-MS simultaneously which indicated the complementary of the two kinds of detection technologies. Therefore, the integration of (1H NMR and UPLC-Q-TOF/MS in metabonomics study provided an approach to identify

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  15. 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.

  16. 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

  17. Glucocorticoids, chronic stress, and obesity.

    Science.gov (United States)

    Dallman, Mary F; Pecoraro, Norman C; La Fleur, Susanne E; Warne, James P; Ginsberg, Abigail B; Akana, Susan F; Laugero, Kevin C; Houshyar, Hani; Strack, Alison M; Bhatnagar, Seema; Bell, Mary E

    2006-01-01

    Glucocorticoids either inhibit or sensitize stress-induced activity in the hypothalamo-pituitary-adrenal (HPA) axis, depending on time after their administration, the concentration of the steroids, and whether there is a concurrent stressor input. When there are high glucocorticoids together with a chronic stressor, the steroids act in brain in a feed-forward fashion to recruit a stress-response network that biases ongoing autonomic, neuroendocrine, and behavioral outflow as well as responses to novel stressors. We review evidence for the role of glucocorticoids in activating the central stress-response network, and for mediation of this network by corticotropin-releasing factor (CRF). We briefly review the effects of CRF and its receptor antagonists on motor outflows in rodents, and examine the effects of glucocorticoids and CRF on monoaminergic neurons in brain. Corticosteroids stimulate behaviors that are mediated by dopaminergic mesolimbic "reward" pathways, and increase palatable feeding in rats. Moreover, in the absence of corticosteroids, the typical deficits in adrenalectomized rats are normalized by providing sucrose solutions to drink, suggesting that there is, in addition to the feed-forward action of glucocorticoids on brain, also a feedback action that is based on metabolic well being. Finally, we briefly discuss the problems with this network that normally serves to aid in responses to chronic stress, in our current overindulged, and underexercised society.

  18. 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...

  19. Mild systemic thermal therapy ameliorates renal dysfunction in a rodent model of chronic kidney disease.

    Science.gov (United States)

    Iwashita, Yoshihiro; Kuwabara, Takashige; Hayata, Manabu; Kakizoe, Yutaka; Izumi, Yuichiro; Iiyama, Junichi; Kitamura, Kenichiro; Mukoyama, Masashi

    2016-06-01

    Thermal therapy has become a nonpharmacological therapy in clinical settings, especially for cardiovascular diseases. However, the practical role of thermal therapy on chronic kidney disease remains elusive. We performed the present study to investigate whether a modified thermal protocol, repeated mild thermal stimulation (MTS), could affect renal damages in chronic kidney disease using a mouse renal ablation model. Mice were subjected to MTS or room temperature (RT) treatment once daily for 4 wk after subtotal nephrectomy (Nx) or sham operation (Sh). We revealed that MTS alleviated renal impairment as indicated by serum creatinine and albuminuria in Nx groups. In addition, the Nx + MTS group showed attenuated tubular histological changes and reduced urinary neutrophil gelatinase-associated lipocalin excretion approximately by half compared with the Nx + RT group. Increased apoptotic signaling, such as TUNEL-positive cell count and cleavage of caspase 3, as well as enhanced oxidative stress were significantly reduced in the Nx + MTS group compared with the Nx + RT group. These changes were accompanied with the restoration of kidney Mn-SOD levels by MTS. Heat shock protein 27, a key molecular chaperone, was phosphorylated by MTS only in Nx kidneys rather than in Sh kidneys. MTS also tended to increase the phosphorylation of p38 MAPK and Akt in Nx kidneys, possibly associated with the activation of heat shock protein 27. Taken together, these results suggest that modified MTS can protect against renal injury in a rodent model of chronic kidney disease.

  20. Chronic stress and immunosenescence: a review.

    Science.gov (United States)

    Bauer, Moisés Evandro

    2008-01-01

    This paper reviews recent work suggesting that human immunosenescence may be closely related to both chronic stress and stress hormones. The age-related immunological changes are also similarly found during chronic stress or glucocorticoid exposure. These data further suggest that endogenous glucocorticoids could be associated with immunosenescence. When compared with young subjects, healthy elders are emotionally distressed in parallel to increased cortisol/dehydroepiandrosterone ratio. Furthermore, chronically stressed elderly subjects may be particularly at risk of stress-related pathology because of further alterations in glucocorticoid-immune signaling. Age-related increase in cortisol/dehydroepiandrosterone ratio could be understood as a major determinant of immunological changes observed during aging. Strictly healthy elders are somewhat protected from chronic stress exposure and show normal cortisol levels and increased T cell function. This information adds a new key dimension to the biology of aging and stress.

  1. Role of chronic stress and depression in periodontal diseases.

    Science.gov (United States)

    Warren, Kimberly R; Postolache, Teodor T; Groer, Maureen E; Pinjari, Omar; Kelly, Deanna L; Reynolds, Mark A

    2014-02-01

    An extensive body of experimental and clinical evidence documents the negative impact of chronic psychological stress and depression on the immune system and health. Chronic stress and depression can result in general dysregulation of the immune system, of both cellular and humoral pathways, which may contribute to pathogenic infection and concomitant periodontal tissue destruction. In general, the evidence is consistent with the hypothesis that stress can modify the host defense and progression of periodontal infections in patients susceptible to periodontitis. However, substantial evidence also indicates that these conditions can mediate risk for disease, including periodontitis, through changes in health-related behaviors, such as oral hygiene, smoking and diet. The unequivocal interpretation of studies has also been hampered, in part, by issues related to conceptualization of stress and depression, as well as commonly associated comorbidities, such as diabetes, that can modify the onset and progression of periodontal disease. In addition, stress and depression appear to fall into a spectrum, ranging from mild to severe, involving a complex interaction of genetic background, coping strategies and environment. Differences in the conceptualization of stress and depression are probably important in assessing associations with other biologic and clinical measures. Future studies are necessary to clarify the complex interactions of chronic stress and depression in periodontal diseases.

  2. 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

  3. Arginines Plasma Concentration and Oxidative Stress in Mild to Moderate COPD

    Science.gov (United States)

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

    2016-01-01

    Background Elevated plasma concentrations of the endogenous nitric oxide synthase (NOS) inhibitor asymmetric dimethylarginine (ADMA) have been observed in respiratory conditions such as asthma and cystic fibrosis. Since oxidative stress has been shown to increase the activity of arginine methylating enzymes, hence increased ADMA synthesis, and to reduce ADMA degrading enzymes, hence increased ADMA concentrations, we assessed methylated arginines concentrations in chronic obstructive pulmonary disease (COPD), a disease characterized by increased oxidative stress. Methods Plasma arginine, ADMA and symmetric dimethylarginine (SDMA), oxidative stress markers (thiobarbituric acid reactive substances, TBARS, and plasma proteins SH, PSH) and antioxidants (taurine and paraoxonase 1, PON1, activity) were measured in 43 COPD patients with mild (n = 29) or moderate (n = 14) disease and 43 age- and sex-matched controls. Results TBARS significantly increased with COPD presence and severity (median 2.93 vs 3.18 vs 3.64 μmol/L, respectively in controls, mild and moderate group, p<0.0001 by ANOVA) whereas PSH decreased (6.69±1.15 vs 6.04±0.85 vs 5.33±0.96 μmol/gr prot, p<0.0001 by ANOVA). Increased ADMA/arginine ratio, primarily due to reduced arginine concentrations, was also observed with COPD presence and severity (median 0.0067 vs 0.0075 vs 0.0100, p<0.0001 by ANOVA). In multiple logistic regression analysis, only TBARS (OR 0.44, 95% CI 0.25–0.77; p = 0.0045) and ADMA/Arginine ratio (OR 1.72, 95% CI 2.27–13.05; p = 0.02) were independently associated with COPD severity. Conclusion COPD presence and severity are associated with increased oxidative stress and alterations in arginine metabolism. The reduced arginine concentrations in COPD may offer a new target for therapeutic interventions increasing arginine availability. PMID:27479314

  4. Chronic effect of ketanserin in mild to moderate essential hypertension.

    Science.gov (United States)

    Woittiez, A J; Wenting, G J; van den Meiracker, A H; Ritsema van Eck, H J; Man in't Veld, A J; Zantvoort, F A; Schalekamp, M A

    1986-02-01

    Ketanserin, an antagonist highly selective for 5-hydroxytryptamine (serotonin) type 2 (S2) receptors, was given as monotherapy in a dose of 40 mg b.i.d. to 24 subjects with mild to moderate essential hypertension. Its effects were evaluated in a placebo-controlled double-blind crossover study. The effect on blood pressure in 18 subjects was monitored by 24-hour ambulatory intra-arterial measurements. Systolic and diastolic intra-arterial pressures were significantly lowered by ketanserin both during the day and at night, whereas heart rate was unchanged. Cuff pressure readings (triplicate measurements) with the London School of Hygiene sphygmomanometer and an automatic device (12 measurements in 1 hour) in the outpatient clinic also showed a significant effect on both supine and standing pressures. No postural hypotension was noted. Ketanserin had no effect on endogenous creatinine clearance, serum cholesterol levels, and the plasma levels of norepinephrine, renin, and aldosterone. The only side effect that was significantly more common with ketanserin than with placebo treatment was an increase in body weight. Ketanserin may have a place in the treatment of mild to moderate essential hypertension.

  5. Gender differences in the enhanced vulnerability of BDNF+/- mice to mild stress.

    Science.gov (United States)

    Advani, Tushar; Koek, Wouter; Hensler, Julie G

    2009-06-01

    Two mild stress paradigms were used in the present study: acute (i.e. three injections of saline over 24 h) and subchronic (i.e. single daily injection of saline for 7 d). These mild stress procedures did not alter the behaviour of wild-type mice in the forced swim test. However, male BDNF+/- mice exhibited increased immobility in the forced swim test after mild stress. This genotypic difference in stress responsivity was also evident in plasma corticosterone levels after a single injection of saline. The behaviour of female mice of either genotype was not altered by mild stress, and there was no genotypic difference in the corticosterone response of female mice to a single saline injection. Male BDNF+/- mice should be a useful model in which to examine behavioural and neurochemical consequences of interactions among genetic and environmental factors implicated in stress-related affective disorders, such as major depression.

  6. The Relation of Mild Traumatic Brain Injury to Chronic Lapses of Attention

    Science.gov (United States)

    Pontifex, Matthew B.; Broglio, Steven P.; Drollette, Eric S.; Scudder, Mark R.; Johnson, Chris R.; O'Connor, Phillip M.; Hillman, Charles H.

    2012-01-01

    We assessed the extent to which failures in sustained attention were associated with chronic mild traumatic brain injury (mTBI) deficits in cognitive control among college-age young adults with and without a history of sport-related concussion. Participants completed the ImPACT computer-based assessment and a modified flanker task. Results…

  7. A critical review of chronic stress effects on spatial learning and memory.

    Science.gov (United States)

    Conrad, Cheryl D

    2010-06-30

    The purpose of this review is to evaluate the effects of chronic stress on hippocampal-dependent function, based primarily upon studies using young, adult male rodents and spatial navigation tasks. Despite this restriction, variability amongst the findings was evident and how or even whether chronic stress influenced spatial ability depended upon the type of task, the dependent variable measured and how the task was implemented, the type and duration of the stressors, housing conditions of the animals that include accessibility to food and cage mates, and duration from the end of the stress to the start of behavioral assessment. Nonetheless, patterns emerged as follows: For spatial memory, chronic stress impairs spatial reference memory and has transient effects on spatial working memory. For spatial learning, however, chronic stress effects appear to be task-specific: chronic stress impairs spatial learning on appetitively motivated tasks, such as the radial arm maze or holeboard, tasks that evoke relatively mild to low arousal components from fear. But under testing conditions that evoke moderate to strong arousal components from fear, such as during radial arm water maze testing, chronic stress appears to have minimal impairing effects or may even facilitate spatial learning. Chronic stress clearly impacts nearly every brain region and thus, how chronic stress alters hippocampal spatial ability likely depends upon the engagement of other brain structures during behavioral training and testing.

  8. Life-time protection against severe heat stress by exposing young Drosophila melanogaster flies to a mild cold stress.

    Science.gov (United States)

    Le Bourg, Éric

    2016-04-01

    Previous studies in the laboratory of the author have shown that subjecting flies to a mild stress (e.g. a cold stress) during the first 2 weeks of adult life can increase lifespan and resistance to severe stresses (e.g. heat and fungal infection) at 6 weeks of age (ca the mean lifespan at 25 °C). This result could either show that a mild stress protects flies against severe stress for the entire life or for a duration of 4 weeks. To clarify the issue, young flies living at 25 °C were pretreated with a cold stress and thereafter transferred at 19 or 22 °C, which increases lifespan. The mild cold stress protected these flies from heat at ages when flies kept at 25 °C are dead, i.e. at 10 weeks of age or 8 weeks after the end of cold stress. Thus, a mild stress protects flies for life, even if the duration of life is increased. Because temperature can strongly vary from day to day in the wild, and lifespan of flies too, it would be a selective advantage if the ability to survive a strong stress after having been subjected to a mild stress would be maintained not only for a few days but for life, whatever its duration could be. If flies would be subjected to a mild stress when living at 25 °C, a temperature change from e.g. 25 to 22 °C would increase their lifespan and they could survive a strong stress at an age when flies kept at 25 °C are dead.

  9. Clinical Studies on Treatment of Chronic Prostatitis with Acupuncture and Mild Moxibustion

    Institute of Scientific and Technical Information of China (English)

    Yu Yang; Kang Jingli; Duan Shumin

    2005-01-01

    To observe the therapeutic effect of acupuncture and mild moxibustion on chronic prostatitis and to probe into the mechanism of the therapy. Two hundred patients with chronic prostatitis were randomly divided into two groups so as to observe respectively the changes in clinical symptoms, count of WBC and lecithin corpuscles in succus prostaticus, prostatic capcules and internal echo, tenderness and elasticity of prostate by palpation before and after treatment. After treatment, a remarkable improvement was found in clinical symptoms, succus prostaticus test and ultrasonic examination in the treatment group with a statistically significant difference (P<0.05) as compared to the control group. The treatment of chronic prostatitis with acupuncture and mild moxibustion can remove the stagnation of succus prostaticus, improve the blood circulation in prostate, inhibit or kill the pathogenic micro-organisms, strengthen or regulate the immune function of the patients, improve local blood circulation, eliminate the accumulation of secretion and relieve the obstruction of the prostatic ducts.

  10. Neural Control of Chronic Stress Adaptation

    Directory of Open Access Journals (Sweden)

    James eHerman

    2013-08-01

    Full Text Available 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 stress reactivity and eventually become maladaptive. The long-term impact of stress is kept in check by the process of habituation, which reduces HPA axis responses upon repeated exposure to homotypic stressors and likely limits deleterious actions of prolonged glucocorticoid secretion. Habituation is regulated by limbic stress-regulatory sites, and is at least in part glucocorticoid feedback-dependent. Chronic stress also sensitizes reactivity to new stimuli. While sensitization may be important in maintaining response flexibility in response to new threats, it may also add to the cumulative impact of glucocorticoids on the brain and body. Finally, unpredictable or severe stress exposure may cause long-term and lasting dysregulation of the HPA axis, likely due to altered limbic control of stress effector pathways. Stress-related disorders, such as depression and PTSD, are accompanied by glucocorticoid imbalances and structural/ functional alterations in limbic circuits that resemble those seen following chronic stress, suggesting that inappropriate processing of stressful information may be part of the pathological process.

  11. Endoplasmic reticulum stress is chronically activated in chronic pancreatitis.

    Science.gov (United States)

    Sah, Raghuwansh P; Garg, Sushil K; Dixit, Ajay K; Dudeja, Vikas; Dawra, Rajinder K; Saluja, Ashok K

    2014-10-03

    The pathogenesis of chronic pancreatitis (CP) is poorly understood. Endoplasmic reticulum (ER) stress has now been recognized as a pathogenic event in many chronic diseases. However, ER stress has not been studied in CP, although pancreatic acinar cells seem to be especially vulnerable to ER dysfunction because of their dependence on high ER volume and functionality. Here, we aim to investigate ER stress in CP, study its pathogenesis in relation to trypsinogen activation (widely regarded as the key event of pancreatitis), and explore its mechanism, time course, and downstream consequences during pancreatic injury. CP was induced in mice by repeated episodes of acute pancreatitis (AP) based on caerulein hyperstimulation. ER stress leads to activation of unfolded protein response components that were measured in CP and AP. We show sustained up-regulation of unfolded protein response components ATF4, CHOP, GRP78, and XBP1 in CP. Overexpression of GRP78 and ATF4 in human CP confirmed the experimental findings. We used novel trypsinogen-7 knock-out mice (T(-/-)), which lack intra-acinar trypsinogen activation, to clarify the relationship of ER stress to intra-acinar trypsinogen activation in pancreatic injury. Comparable activation of ER stress was seen in wild type and T(-/-) mice. Induction of ER stress occurred through pathologic calcium signaling very early in the course of pancreatic injury. Our results establish that ER stress is chronically activated in CP and is induced early in pancreatic injury through pathologic calcium signaling independent of trypsinogen activation. ER stress may be an important pathogenic mechanism in pancreatitis that needs to be explored in future studies.

  12. Investigations into mild electric foot shock stress-induced cognitive enhancement: possible role of angiotensin neuropeptides.

    Science.gov (United States)

    Bali, Anjana; Singh, Nirmal; Jaggi, Amteshwar Singh

    2013-09-01

    This study was designed to investigate the role of angiotensin neuropeptides in mild electric foot shock stress-induced cognitive enhancement in mice. Mild stress was induced by applying mild electric foot shocks of 0.15 mA intensity for 0.5 s. The stress-induced alteration in cognition was assessed using a Morris water maze test. The animals were subjected to mild electric foot shocks 5 min before we recorded escape latency time (ELT), an index of learning, during the first 4 days of a 5-day trial in the Morris water maze. The time spent in target quadrant (TSTQ), an index of retrieval, was noted on the fifth day without prior administration of electric foot shock. The angiotensin-converting enzyme inhibitor lisinopril (5, 10 and 20 mg/kg), and telmisartan (1, 2 and 5 mg/kg), an angiotensin II receptor blocker, were employed to assess the role of angiotensin neuropeptides. The application of mild electric shocks significantly decreased ELT and increased TSTQ, indicating enhancement in stress-induced learning and memory. However, administration of lisinopril and telmisartan significantly attenuated the stress-induced decrease in ELT and increase in TSTQ. It may be concluded that mild electric foot shock-induced stress triggers the release of angiotensin neuropeptides that may be responsible for memory enhancement.

  13. 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.

  14. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Institute of Scientific and Technical Information of China (English)

    Massimo; Sartori; Silvano; Andorno; Angelo; Rossini; Renzo; Boldorini; Cristina; Bozzola; Stefania; Carmagnola; Mario; Del; Piano; Emanuele; Albano

    2010-01-01

    AIM:To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C(CHC). METHODS:We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to,or unsuitable for,antiviral therapy who underwent mild iron depletion(ferritin≤70 ng/mL) by long-term phlebotomy.Histological improvement,as defined by at least one point reduction in the staging score or,in case...

  15. 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

  16. 甘丙肽2型受体激动剂对慢性温和应激模型大鼠抑郁样行为的影响%Effects of Galanin Receptor 2 Agonist on Depression-like Behavior in Chronic Mild Stress Model Rats

    Institute of Scientific and Technical Information of China (English)

    张攀; 刘博; 王彤; 李慧; 杨予涛; 徐志卿

    2016-01-01

    Objective To explore the effect of intracerebroventricular injection of AR-M1896, a galanin receptor 2 agonist, on depres-sion-like behavior in rat chronic mild stress (CMS) model. Methods 48 Sprague-Dawley rats were randomly assigned into control group, CMS group, CMS artificial cerebrospinal fluid (aCSF) group and CMS AR-M1896 group equally. The control group received no interven-tion, and the other groups were established chronic mild stress model. After six-week of stress, forced swim test and sucrose preference test were conducted to identify the CMS rats. AR-M1896 or aCSF was injected into the lateral ventricle of CMS AR-M1896 group and CMS aC-SF group, respectively. The immobility time and climbing time in the forced swim test were analysed, and the sucrose consumption percent-age in the sucrose preference test was measured. Results The immobility time decreased (F=11.998, P<0.01), climbing time increased (F=8.268, P<0.05), and the sucrose consumption percentage increased (F=10.352, P<0.01) in CMS AR-M1896 group, compared with CMS aC-SF group. Conclusion Intracerebroventricular administration of galanin receptor 2 agonist AR-M1896 is effective on depression in CMS model rats.%目的 侧脑室注射甘丙肽2型受体(GalR2)激动剂AR-M1896,探讨其对慢性温和应激模型(CMS)大鼠抑郁样行为的影响.方法 48只Sprague-Dawley大鼠随机等分为对照组、CMS组、CMS人工脑脊液(aCSF)组、CMS AR-M1896组.对照组不作任何处理,其他3组制备大鼠慢性温和应激模型.应激6周后,通过强迫游泳及糖水偏好实验验证抑郁样行为;挑选造模成功大鼠,CMS aCSF组和CMS AR-M1896组侧脑室分别注射aCSF和AR-M1896.观察强迫游泳实验中的不动时间、攀爬时间,以及糖水偏好实验中的糖水饮用百分比.结果 与CMS aCSF组相比,CMS AR-M1896组不动时间明显缩短(F=11.998,P<0.01),攀爬时间延长(F=8.268,P<0.05),糖水饮用百分比明显增加(F=10.352,P<0.01).结论

  17. Pathogenesis of Chronic Hyperglycemia: From Reductive Stress to Oxidative Stress

    Directory of Open Access Journals (Sweden)

    Liang-Jun Yan

    2014-01-01

    Full Text Available Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH, respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.

  18. Resilience to chronic stress is mediated by hippocampal brain-derived neurotrophic factor.

    Science.gov (United States)

    Taliaz, Dekel; Loya, Assaf; Gersner, Roman; Haramati, Sharon; Chen, Alon; Zangen, Abraham

    2011-03-23

    Chronic stress is a trigger for several psychiatric disorders, including depression; however, critical individual differences in resilience to both the behavioral and the neurochemical effects of stress have been reported. A prominent mechanism by which the brain reacts to acute and chronic stress is activation of the hypothalamic-pituitary-adrenal (HPA) axis, which is inhibited by the hippocampus via a polysynaptic circuit. Alterations in secretion of stress hormones and levels of brain-derived neurotrophic factor (BDNF) in the hippocampus were implicated in depression and the effects of antidepressant medications. However, the potential role of hippocampal BDNF in behavioral resilience to chronic stress and in the regulation of the HPA axis has not been evaluated. In the present study, Sprague Dawley rats were subjected to 4 weeks of chronic mild stress (CMS) to induce depressive-like behaviors after lentiviral vectors were used to induce localized BDNF overexpression or knockdown in the hippocampus. The behavioral outcome was measured during 3 weeks after the CMS procedure, then plasma samples were taken for measurements of corticosterone levels, and finally hippocampal tissue was taken for BDNF measurements. We found that hippocampal BDNF expression plays a critical role in resilience to chronic stress and that reduction of hippocampal BDNF expression in young, but not adult, rats induces prolonged elevations in corticosterone secretion. The present study describes a mechanism for individual differences in responses to chronic stress and implicates hippocampal BDNF in the development of neural circuits that control adequate stress adaptations.

  19. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Science.gov (United States)

    Sagai, Masaru; Bocci, Velio

    2011-12-20

    The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not.Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB), resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2). Nrf2 then induces the transcription of antioxidant response elements (ARE). Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr), catalase (CAT), heme-oxygenase-1 (HO-1), NADPH-quinone-oxidoreductase (NQO-1), phase II enzymes of drug metabolism and heat shock proteins (HSP). Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT) and activated protein-1 (AP-1).Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1α (HIF-1a), which is also induced via moderate oxidative

  20. Mechanisms of Action Involved in Ozone Therapy: Is healing induced via a mild oxidative stress?

    Directory of Open Access Journals (Sweden)

    Sagai Masaru

    2011-12-01

    Full Text Available Abstract The potential mechanisms of action of ozone therapy are reviewed in this paper. The therapeutic efficacy of ozone therapy may be partly due the controlled and moderate oxidative stress produced by the reactions of ozone with several biological components. The line between effectiveness and toxicity of ozone may be dependent on the strength of the oxidative stress. As with exercise, it is well known that moderate exercise is good for health, whereas excessive exercise is not. Severe oxidative stress activates nuclear transcriptional factor kappa B (NFκB, resulting in an inflammatory response and tissue injury via the production of COX2, PGE2, and cytokines. However, moderate oxidative stress activates another nuclear transcriptional factor, nuclear factor-erythroid 2-related factor 2 (Nrf2. Nrf2 then induces the transcription of antioxidant response elements (ARE. Transcription of ARE results in the production of numerous antioxidant enzymes, such as SOD, GPx, glutathione-s-transferase(GSTr, catalase (CAT, heme-oxygenase-1 (HO-1, NADPH-quinone-oxidoreductase (NQO-1, phase II enzymes of drug metabolism and heat shock proteins (HSP. Both free antioxidants and anti-oxidative enzymes not only protect cells from oxidation and inflammation but they may be able to reverse the chronic oxidative stress. Based on these observations, ozone therapy may also activate Nrf2 via moderate oxidative stress, and suppress NFκB and inflammatory responses. Furthermore, activation of Nrf2 results in protection against neurodegenerative diseases, such as Alzheimer's and Parkinson's diseases. Mild immune responses are induced via other nuclear transcriptional factors, such as nuclear factor of activated T-cells (NFAT and activated protein-1 (AP-1. Additionally, the effectiveness of ozone therapy in vascular diseases may also be explained by the activation of another nuclear transcriptional factor, hypoxia inducible factor-1α (HIF-1a, which is also induced via

  1. Psychoneuroendocrinological studies on chronic stress and depression.

    Science.gov (United States)

    Tafet, Gustavo E; Smolovich, Jaime

    2004-12-01

    The adaptive response to stress is characterized by activation of neural and neuroendocrine cascades mediated mainly by the noradrenergic/sympathetic and limbic-hypothalamic-pituitary-adrenal (HPA) systems, respectively. Chronic psychosocial stress has long been associated with the origin and development of depression, where increased levels of cortisol have been observed in both conditions. In this regard, increased levels of cortisol could be directly involved in the mood changes observed in depression, and direct connections between these and alterations of the serotonergic neurotransmission have been also proposed. Therefore, we investigated the potential link between alterations of the limbic-HPA system with the serotonergic hypothesis of depression at both the molecular and clinical levels. Our findings support the notion that chronic psychosocial stress may lead to depression in certain individuals depending on the psychobiological background and their particular psychological resources. Therefore, certain interventions aimed at normalization of the HPA system could potentially prevent the development of depression in chronically stressed subjects. This would be possible through either pharmacological interventions or psychotherapeutic strategies, such as cognitive therapy, aimed at improving resilience and controllability in stressful situations.

  2. Beneficial effects of mild stress (hormetic effects): dietary restriction and health.

    Science.gov (United States)

    Kouda, Katsuyasu; Iki, Masayuki

    2010-01-01

    Hormesis is defined as a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition, and has been recognized as representing an overcompensation for mild environmental stress. The beneficial effects of mild stress on aging and longevity have been studied for many years. In experimental animals, mild dietary stress (dietary restriction, DR) without malnutrition delays most age-related physiological changes, and extends maximum and average lifespan. Animal studies have also demonstrated that DR can prevent or lessen the severity of cancer, stroke, coronary heart disease, autoimmune disease, allergy, Parkinson's disease and Alzheimer's disease. The effects of DR are considered to result from hormetic mechanisms. These effects were reported by means of various DR regimens, such as caloric restriction, total-nutrient restriction, alternate-day fasting, and short-term fasting. Mild dietary stress, including restriction of amount or frequency of intake, is the essence of DR. For more than 99% of their history, humans lived as hunter-gatherers and adapted to restrictions in their food supply. On the other hand, an oversufficiency of food for many today has resulted in the current global epidemic of obesity and obesity-related diseases. DR may be used, therefore, as a novel approach for therapeutic intervention in several diseases, when detailed information about effects of mild dietary stress on human health is obtained from clinical trials.

  3. Mild maternal stress disrupts associative learning and increases aggression in offspring.

    Science.gov (United States)

    Eaton, L; Edmonds, E J; Henry, T B; Snellgrove, D L; Sloman, K A

    2015-05-01

    Maternal stress has been shown to affect behaviour of offspring in a wide range of animals, but this evidence has come from studies that exposed gestating mothers to acute or severe stressors, such as restraint or exposure to synthetic stress hormones. Here we show that exposure of mothers to even a mild stressor reduces associative learning and increases aggression in offspring. Female guppies were exposed to routine husbandry procedures that produced only a minimal, non-significant, elevation of the stress hormone cortisol. In contrast to controls, offspring from mothers that experienced this mild stress failed to learn to associate a colour cue and food reward, and showed a greater amount of inter-individual variation in behaviour compared with control offspring. This mild stress also resulted in offspring that were more aggressive towards their own mirror image than controls. While it is possible that these results could represent the transmission of beneficial maternal characteristics to offspring born into unpredictable environments, the potential for mild maternal stress to affect offspring performance also has important implications for research into the trans-generational effects of stress.

  4. Calculation of Wave Radiation Stress in Combination with Parabolic Mild Slope Equation

    Institute of Scientific and Technical Information of China (English)

    ZHENG Yonghong; SHEN Yongming; QIU Dahong

    2000-01-01

    A new method for the calculation of wave radiation stress is proposed by linking the expressions for wave radiation stress with the variables in the parabolic mild slope equation. The governing equations are solved numerically by the finite difference method. Numerical results show that the new method is accurate enough, can be efficiently solved with little programming effort, and can be applied to the calculation of wave radiation stress for large coastal areas.

  5. Improvement ofSchisandrae Fructusprocessed products on depressive mice induced by chronic unpredictable mild stress%五味子不同炮制品对小鼠慢性不可预知性应激抑郁的改善作用

    Institute of Scientific and Technical Information of China (English)

    荆然; 李慧峰; 程艳刚; 裴妙荣

    2016-01-01

    Objective To evaluate the improvement ofSchisandrae Fructusprocessed products on depression of mice induced by chronic unpredictable mild stress.Methods ICR mice were randomly divided into control group, model group, fluoxetine group, andSchisandrae Fructus,Schisandrae Fructusprocessed with alcohol, andSchisandrae Fructusprocessed with wine groups, and each group had 10 mice. Mice in the control and model groups were ig administered with distilled water. Mice in the fluoxetine group were ig administered with Fluoxetine Hydrochloride Dispersible Tablets 3.3 mg/kg. Mice in the Schisandrae Fructus groups were ig administered withSchisandrae Fructus1.0 g/kg with volume of 10 mL/kg. Ten kinds of unpredictable stimulations were adopted to establish the model of chronic unpredictable mild stress after last administration 1 h for 28 d. Behaviors of depressive mice in open field test, tail suspression test, and forced swimming test were observed. The contents of 5-HT, DA, and CORT in serum were determined by Enzyme-linked immunosorbent assay (ELISA) method. Results were analyzed by comprehensive analysis method. Results Compared with the model group, the open field stand times and open central grid crossing times were increased, but the time of hanging tail and room temperature forced swimming were decreased in theSchisandrae Fructus group (P< 0.05, 0.01). There were no differences on open field stand times and open central grid crossing times inSchisandrae Fructusprocessed with alcohol and wine groups, but the time of hanging tail and room temperature forced swimming were decreased (P< 0.05). Compared with the model group, contents of 5-HT and DA in serum of depressive mice were increased, but the contents of CORT in serum were decreased in the Schisandrae Fructus group (P< 0.01). The contents of 5-HT in serum of depressive mice were increased, but the contents of CORT in serum were decreased in theSchisandrae Fructusprocessed with alcohol and wine groups (P< 0.05, 0

  6. White Matter Abnormalities are Associated with Chronic Postconcussion Symptoms in Blast-Related Mild Traumatic Brain Injury

    Science.gov (United States)

    Miller, Danielle R.; Hayes, Jasmeet P.; Lafleche, Ginette; Salat, David H.; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are non-specific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of co-morbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) Veterans were assigned to one of three groups including a blast-exposed no-TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI−LOC), and a blast-related mTBI with LOC group (mTBI+LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI+LOC group had more spatially heterogeneous white matter abnormalities than those in the no-TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI+LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS. PMID:26497829

  7. White matter abnormalities are associated with chronic postconcussion symptoms in blast-related mild traumatic brain injury.

    Science.gov (United States)

    Miller, Danielle R; Hayes, Jasmeet P; Lafleche, Ginette; Salat, David H; Verfaellie, Mieke

    2016-01-01

    Blast-related mild traumatic brain injury (mTBI) is a common injury among Iraq and Afghanistan military veterans due to the frequent use of improvised explosive devices. A significant minority of individuals with mTBI report chronic postconcussion symptoms (PCS), which include physical, emotional, and cognitive complaints. However, chronic PCS are nonspecific and are also associated with mental health disorders such as posttraumatic stress disorder (PTSD). Identifying the mechanisms that contribute to chronic PCS is particularly challenging in blast-related mTBI, where the incidence of comorbid PTSD is high. In this study, we examined whether blast-related mTBI is associated with diffuse white matter changes, and whether these neural changes are associated with chronic PCS. Ninety Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans were assigned to one of three groups including a blast-exposed no--TBI group, a blast-related mTBI without loss of consciousness (LOC) group (mTBI--LOC), and a blast-related mTBI with LOC group (mTBI + LOC). PCS were measured with the Rivermead Postconcussion Questionnaire. Results showed that participants in the mTBI + LOC group had more spatially heterogeneous white matter abnormalities than those in the no--TBI group. These white matter abnormalities were significantly associated with physical PCS severity even after accounting for PTSD symptoms, but not with cognitive or emotional PCS severity. A mediation analysis revealed that mTBI + LOC significantly influenced physical PCS severity through its effect on white matter integrity. These results suggest that white matter abnormalities are associated with chronic PCS independent of PTSD symptom severity and that these abnormalities are an important mechanism explaining the relationship between mTBI and chronic physical PCS.

  8. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats.

    Science.gov (United States)

    Figueroa-García, María del Consuelo; Espinosa-García, María Teresa; Martinez-Montes, Federico; Palomar-Morales, Martín; Mejía-Zepeda, Ricardo

    2015-01-01

    It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S) in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.

  9. Even a Chronic Mild Hyperglycemia Affects Membrane Fluidity and Lipoperoxidation in Placental Mitochondria in Wistar Rats.

    Directory of Open Access Journals (Sweden)

    María del Consuelo Figueroa-García

    Full Text Available It is known the deleterious effects of diabetes on embryos, but the effects of diabetes on placenta and its mitochondria are still not well known. In this work we generated a mild hyperglycemia model in female wistar rats by intraperitoneal injection of streptozotocin in 48 hours-old rats. The sexual maturity onset of the female rats was delayed around 6-7 weeks and at 16 weeks-old they were mated, and sacrificed at day 19th of pregnancy. In placental total tissue and isolated mitochondria, the fatty acids composition was analyzed by gas chromatography, and lipoperoxidation was measured by thiobarbituric acid reactive substances. Membrane fluidity in mitochondria was measured with the excimer forming probe dipyrenylpropane and mitochondrial function was measured with a Clark-type electrode. The results show that even a chronic mild hyperglycemia increases lipoperoxidation and decreases mitochondrial function in placenta. Simultaneously, placental fatty acids metabolism in total tissue is modified but in a different way than in placental mitochondria. Whereas the chronic mild hyperglycemia induced a decrease in unsaturated to saturated fatty acids ratio (U/S in placental total tissue, the ratio increased in placental mitochondria. The measurements of membrane fluidity showed that fluidity of placenta mitochondrial membranes increased with hyperglycemia, showing consistency with the fatty acids composition through the U/S index. The thermotropic characteristics of mitochondrial membranes were changed, showing lower transition temperature and activation energies. All of these data together demonstrate that even a chronic mild hyperglycemia during pregnancy of early reproductive Wistar rats, generates an increment of lipoperoxidation, an increase of placental mitochondrial membrane fluidity apparently derived from changes in fatty acids composition and consequently, mitochondrial malfunction.

  10. Diagnosis of mild chronic pancreatitis (Cambridge classification): Comparative study using secretin injection-magnetic resonance cholangiopancreatography and endoscopic retrograde pancreatography

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    AIM: To investigate the usefulness of secretin injection MRCP for the diagnosis of mild chronic pancreatitis. METHODS: Sixteen patients having mild chronic pancreatitis according to the Cambridge classification and 12 control subjects with no abnormal findings on the pancreatogram were examined for the diagnostic accuracy of secretin injection-MRCP regarding abnormal branch pancreatic ducts associated with mild chronic pancreatitis (Cambridge Classification), using endoscopic retrograde cholangiopancreatography (ERCP) for comparison. RESULTS: The sensitivity and specificity for abnormal branch pancreatic ducts determined by two reviewers were respectively 55%-63% and 75%-83% in the head, 57%-64% and 82%-83% in the body, and 44%-44%and 72%-76% in the tail of the pancreas. The sensitivity and specificity for mild chronic pancreatitis were 56%-63% and 92%-92%, respectively. Interobserver abnormal branch pancreatic duct and of mild chronic pancreatitis was good to excellent. CONCLUSION: Secretin injection-MRCP might be useful for the diagnosis of mild chronic pancreatitis.

  11. Psychosocial Determinants of Chronic Stress in Nursing

    Science.gov (United States)

    1987-12-22

    and mental exhaustion ( Maslach , 1979; Pines & Aronson, 1980). Signs of physical exhaustion are chronic fatigue, weakness, and weariness. Accident...studies of nurses on the cumulative effects of dealing repeatedly with suffering and death of patients have not been done (Davidson & Jackson , 1985). It... Maslach , C. ~1979). The burn-out syndrome and patient care. In c. G~rf1eld (Ed.), Stress and survival (pp. 111-120). St. LOU1S! Mosby. Maslach , .c

  12. Effects of exercise on behavior and serum cortisol in depression due to chronic mild stress%不同时程游泳运动对抑郁症模型大鼠行为及血清皮质醇的影响

    Institute of Scientific and Technical Information of China (English)

    何松彬; 王小同; 唐闻捷

    2008-01-01

    目的 观察不同时程游泳运动对抑郁症模型大鼠行为及血清皮质醇的影响.方法 选取48只SD大鼠随机分为3个大组,每个大组各设3个亚组(每个亚组6只大鼠),第一大组观察造模时运动对大鼠的影响(造模伴运动组),包括空白对照组、造模对照组、造模伴运动组;第二大组观察造模后运动对大鼠的影响(造模后运动组),包括空白对照组、造模对照组、造模后运动组;第三大组观察造模前运动对大鼠的影响(造模前运动组),包括空白对照组、造模对照组、造模前运动组(造模后运动组与造模前运动组为同一组).所有造模大鼠均给予21 d慢性轻度不可预见性应激,记录大鼠旷野试验、糖水试验相关数据,用放射免疫法测定血清皮质醇含量.结果 造模可使大鼠出现糖水摄入减少、糖水偏爱度降低,在旷野试验中水平运动能力减弱、垂直运动能力减弱、排粪便数增加.造模伴运动组大鼠上述现象得到抑制,造模前运动组及造模后运动组的大鼠均未能显示抑制现象,造模可使大鼠血皮质醇含量升高,造模伴运动组及造模前运动组能有效降低血清皮质醇含量,其中造模伴运动组尤为明显.结论 不同时程的游泳运动对抑郁症模型大鼠行为学及血清皮质醇具有不同的影响作用;运动可以降低血清皮质醇含量,并且具有一定的累积效应;运动对抑郁症状的改变以即刻作用为主,没有长期累积作用.%Objective To investigate the effects of exercise on behavior and serum cortisol levels in depression caused by chronic,unpredictable,mild stress(CUMS).Methods Forty-eight male Sprague-Dawley rats were randomly divided into 3 groups:A,B and C.Each group was then divided into 3 subgroups:a blank control subgroup,a model subgroup,and an intervention subgroup.CUMS such as unpredictable forced swimming in cold water,electric stimulation of the animals'feet and shaking of the

  13. Cytoprotective effects of mild plasma-activated medium against oxidative stress in human skin fibroblasts

    Science.gov (United States)

    Horiba, Minori; Kamiya, Tetsuro; Hara, Hirokazu; Adachi, Tetsuo

    2017-01-01

    Non-thermal atmospheric pressure plasma (NTAPP) has recently been applied to living cells and tissues and has emerged as a novel technology for medical applications. NTAPP affects cells not only directly, but also indirectly with previously prepared plasma-activated medium (PAM). The objective of this study was to demonstrate the preconditioning effects of “mild PAM” which was prepared under relatively mild conditions, on fibroblasts against cellular injury generated by a high dose of hydrogen peroxide (H2O2). We observed the preconditioning effects of mild PAM containing approximately 50 μM H2O2. Hydrogen peroxide needs to be the main active species in mild PAM for it to exert preconditioning effects because the addition of catalase to mild PAM eliminated these effects. The nuclear translocation and recruitment of nuclear factor erythroid 2-related factor 2 (Nrf2) to antioxidant response elements (ARE) in heme oxygenase 1 (HO-1) promoters and the up-regulation of HO-1 were detected in fibroblasts treated with mild PAM. The addition of ZnPP, a HO-1-specific inhibitor, or the knockdown of Nrf2 completely abrogated the preconditioning effects. Our results demonstrate that mild PAM protects fibroblasts from oxidative stress by up-regulating HO-1, and the H2O2-induced activation of the Nrf2-ARE pathway needs to be involved in this reaction. PMID:28169359

  14. Responses of KT2440 Pseudomonas putida to mild water stress

    DEFF Research Database (Denmark)

    Gülez, Gamze

    betydningen af flagellær motilitet og produktion af EPS under matric stess undersøgt ved brug af den såkaldte Porous Surface Model (PSM), som genererer væske-filmens effekter ved kontrol af !m. Det blev vist, at flagellær motilitet var begrænset under matric stress; Pseudomonas putida KT2440 kolonier udviste...... overflade-kolonidannelse under matric stress. Et af hovedformålene med denne afhandling var at forbedre PSM-metoden, således at rækken af matric potentials udvides (dvs. ned til -1.5 MPa, vegetations-visnings-punktet), idet det nuværende spektrum af matric potentials, der kan genereres med PSM-metoden, er...... smalt og nærmest begrænset til 1 m H2O (10 kPa). Med dette formål modificerede vi PSM-metoden, sådan at den ønskede !m kan fastsættes svarende til den negative værdi af det givne pneumatiske tryk. Denne modificerede model har vi kaldt Pressurized Porous Surface Model (PPSM). Gennem validering af...

  15. 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.

  16. 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

  17. Assessing posttraumatic stress disorder in children with mild to borderline intellectual disabilities

    NARCIS (Netherlands)

    Mevissen, E.H.M.; Didden, H.C.M.; Korzilius, H.P.L.M.; Jongh, A. de

    2016-01-01

    Background: Evidence suggests that children with mild to borderline intellectual disabilities (MBID; IQ 50-85) have an elevated risk for both being exposed to potentially traumatic events and developing a post-traumatic stress disorder (PTSD). In this target group, PTSD often remains undiscovered du

  18. Assessing posttraumatic stress disorder in children with mild to borderline intellectual disabilities

    NARCIS (Netherlands)

    Mevissen, L.; Didden, R.; Korzilius, H.; de Jongh, A.

    2016-01-01

    Background: Evidence suggests that children with mild to borderline intellectual disabilities (MBID; IQ 50–85) have an elevated risk for both being exposed to potentially traumatic events and developing a posttraumatic stress disorder (PTSD). In this target group, PTSD often remains undiscovered due

  19. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L;

    1995-01-01

    /I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

  20. Effects of the chronic restraint stress induced depression on reward-related learning in rats.

    Science.gov (United States)

    Xu, Pan; Wang, Kezhu; Lu, Cong; Dong, Liming; Chen, Yixi; Wang, Qiong; Shi, Zhe; Yang, Yanyan; Chen, Shanguang; Liu, Xinmin

    2017-03-15

    Chronic mild or unpredictability stress produces a persistent depressive-like state. The main symptoms of depression include weight loss, despair, anhedonia, diminished motivation and mild cognition impairment, which could influence the ability of reward-related learning. In the present study, we aimed to evaluate the effects of chronic restraint stress on the performance of reward-related learning of rats. We used the exposure of repeated restraint stress (6h/day, for 28days) to induce depression-like behavior in rats. Then designed tasks including Pavlovian conditioning (magazine head entries), acquisition and maintenance of instrumental conditioning (lever pressing) and goal directed learning (higher fixed ratio schedule of reinforcement) to study the effects of chronic restraint stress. The results indicated that chronic restraint stress influenced rats in those aspects including the acquisition of a Pavlovian stimulus-outcome (S-O) association, the formation and maintenance of action-outcome (A-O) causal relation and the ability of learning in higher fixed ratio schedule. In conclusion, depression could influence the performances in reward-related learning obviously and the series of instrumental learning tasks may have potential as a method to evaluate cognitive changes in depression.

  1. Stress as a diagnostic challenge for postconcussive symptoms: sequelae of mild traumatic brain injury or physiological stress response.

    Science.gov (United States)

    Hanna-Pladdy, B; Berry, Z M; Bennett, T; Phillips, H L; Gouvier, W D

    2001-08-01

    There is considerable controversy regarding whether persistent postconcussive symptoms (PCS) are injury-specific, in a subgroup of individuals after mild traumatic brain injury (TBI). The following findings have contributed to this controversy: (1) The base rate of PCS in mild TBI is comparable to uninjured controls; and (2) The severity of PCS covary with daily stress levels (Gouvier, Cubic, Jones, Brantley, & Cutlip, 1992). We examined this relationship further by evaluating the effects of experimental conditions of stress or relaxation on individuals with TBI and uninjured control subjects, with low and high PCS endorsement. We evaluated psychophysiological parameters, neuropsychological performance, and changes in PCS and stress perception. In our study, subjects with TBI increased PCS after engaging in cognitively challenging tasks, and demonstrated significant autonomic changes in the stress condition. Symptomatic TBI subjects exposed to high stress had increases in PCS complaints, decreased speed of information processing, and subtle memory deficits. Our results suggest that PCS are injury-specific and that individuals with a history of TBI are susceptible to the effects of stress. Relaxation training including breathing retraining may be an effective means of decreasing PCS and cognitive complaints in subjects with mild TBI.

  2. Insulin resistance and hyperinsulinaemia in mild to moderate progressive chronic renal failure and its association with aerobic work capacity

    DEFF Research Database (Denmark)

    Eidemak, I; Feldt-Rasmussen, B; Kanstrup, I L

    1995-01-01

    Tissue sensitivity to insulin and aerobic work capacity was measured in patients with mild to moderate progressive chronic renal failure. Twenty-nine non-diabetic patients with a glomerular filtration rate of 25 ml.min-1.1.73 m-2 (11-43) (median, range) and 15 sex, age, and body mass index matched....../I ratio in both groups. In conclusion, not only patients with end-stage chronic renal failure but also those with mild to moderate progressive chronic renal failure are insulin resistant and hyperinsulinaemic. The tissue sensitivity to insulin is correlated to the maximal aerobic work capacity suggesting...

  3. Phlebotomy improves histology in chronic hepatitis C males with mild iron overload

    Science.gov (United States)

    Sartori, Massimo; Andorno, Silvano; Rossini, Angelo; Boldorini, Renzo; Bozzola, Cristina; Carmagnola, Stefania; Piano, Mario Del; Albano, Emanuele

    2010-01-01

    AIM: To investigate the usefulness of mild iron depletion and the factors predictive for histological improvement following phlebotomy in Caucasians with chronic hepatitis C (CHC). METHODS: We investigated 28 CHC Caucasians with persistently elevated serum aminotransferase levels and non responders to, or unsuitable for, antiviral therapy who underwent mild iron depletion (ferritin ≤ 70 ng/mL) by long-term phlebotomy. Histological improvement, as defined by at least one point reduction in the staging score or, in case of unchanged stage, as at least two points reduction in the grading score (Knodell), was evaluated in two subsequent liver biopsies (before and at the end of phlebotomy, 48 ± 16 mo apart). RESULTS: Phlebotomy showed an excellent safety profile. Histological improvement occurred in 12/28 phlebotomized patients. Only males responded to phlebotomy. At univariate logistic analysis alcohol intake (P = 0.034), high histological grading (P = 0.01) and high hepatic iron concentration (HIC) (P = 0.04) before treatment were associated with histological improvement. Multivariate logistic analysis showed that in males high HIC was the only predictor of histological improvement following phlebotomy (OR = 1.41, 95% CI: 1.03-1.94, P = 0.031). Accordingly, 12 out of 17 (70%) patients with HIC ≥ 20 μmol/g showed histological improvements at the second biopsy. CONCLUSION: Male CHC Caucasian non-responders to antiviral therapy with low-grade iron overload can benefit from mild iron depletion by long-term phlebotomy. PMID:20128028

  4. Applying a traumatic stress approach to understanding PCS following pediatric mild TBI.

    Science.gov (United States)

    Donlon, Katharine; Jones, Russell T

    2015-01-01

    Pediatric traumatic brain injury is a significant public health concern affecting hundreds of thousands of children each year. The majority of children who sustain traumatic brain injuries are classified as having a mild traumatic brain injury, and a subset of these children go on to experience persistent physical, cognitive, and emotional symptoms. These symptoms, known as postconcussive symptoms, can endure for months and even years after injury. The outcomes of mild traumatic brain injury are variable and not well understood for a small percentage of children who experience persistent symptoms. The current article explores the potential influence of children's posttraumatic stress symptoms on persistent postconcussive symptoms. Despite the high incidence of posttraumatic stress symptoms after pediatric accidental injury, they have not yet been identified as an important factor for consideration in the understanding of pediatric postconcussive outcomes. The article will review the literature on posttraumatic stress and postconcussive symptoms after pediatric injury and consider neurobiological and cognitive factors to propose a model explaining a pathway through which posttraumatic stress reactions may serve as the mechanism for the expression and maintenance of postconcussive symptoms after mild traumatic brain injury. The clinical implications for the proposed relationship between posttraumatic stress symptoms and postconcussive symptoms are considered prior to the conclusion of the article, which acknowledges limitations in the current literature and provides suggestions for future research.

  5. Cognitive and neuroinflammatory consequences of mild repeated stress are exacerbated in aged mice

    Science.gov (United States)

    Buchanan, J.B.; Sparkman, N.L.; Chen, J.; Johnson, R.W.

    2008-01-01

    Summary Peripheral immune stimulation as well as certain types of psychological stress increases brain levels of inflammatory cytokines such as interleukin-1β (IL-1β), IL-6 and tumor necrosis factor α (TNFα). We have demonstrated that aged mice show greater increases in central inflammatory cytokines, as well as greater cognitive deficits, compared to adults in response to peripheral lipopolysaccharide (LPS) administration. Because aged mice are typically more sensitive to systemic stressors such as LPS, and certain psychological stressors induce physiological responses similar to those that follow LPS, we hypothesized that aged mice would be more sensitive to the physiological and cognitive effects of mild stress than adult mice. Here, adult (3–5 mo) and aged (22–23 mo) male BALB/c mice were trained in the Morris water maze for 5 days. Mice were then exposed to a mild restraint stress of 30 minutes before being tested in a working memory version of the water maze over a 3 day period. On day 4 mice were stressed and then killed for collection of blood and brain. In a separate group of animals, mice were killed immediately after one, two or three 30 min restraint sessions and blood for peripheral corticosterone and cytokine protein measurement, and brains were dissected for central cytokine mRNA measurement. Stress disrupted spatial working memory in both adult and aged mice but to a much greater extent in the aged mice. In addition, aged mice showed an increase in stress-induced expression of hippocampal IL-1β mRNA and MHC class II protein compared to non-stressed controls while expression in adult mice was unaffected by stress. These data show that aged mice are more sensitive to both the cognitive and inflammatory effects of mild stress than are adult mice and suggest a possible a role for IL-1β. PMID:18407425

  6. 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.

  7. 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

  8. Domains of Chronic Stress and Suicidal Behaviors among Inpatient Adolescents

    Science.gov (United States)

    Pettit, Jeremy W.; Green, Kelly L.; Grover, Kelly E.; Schatte, Dawnelle J.; Morgan, Sharon T.

    2011-01-01

    Little is known about the role of chronic stress in youth suicidal behaviors. This study examined the relations between specific domains of chronic stress and suicidal behaviors among 131 inpatient youth (M age = 15.02 years) who completed measures of stress, suicidal ideation, suicide attempt, and suicide intent. After controlling for…

  9. 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

  10. Influence on the Expression of TRH in Hypothalamus of Rats with Chronic Unpredictable Mild Stress-induced Depression by Different Electro-acupuncture Treatment%不同电针对慢性应激抑郁模型大鼠下丘脑促甲状腺激素释放激素表达的影响

    Institute of Scientific and Technical Information of China (English)

    莫雨平; 李志刚; 姚海江; 宋洪涛; 陈万顺; 王鑫; 加吾拉·阿不力孜; 许安萍; 唐银杉; 韩向博

    2014-01-01

    目的:观察不同电针对慢性应激抑郁模型( CUMS)大鼠下丘脑中促甲状腺激素释放激素( TRH)表达的影响,探讨TRH在大鼠实验性抑郁症发病过程中的作用机制及不同电针干预对其的影响。方法:将60只清洁健康雄性SD大鼠,随机分为正常组、模型组、脉冲电针组、音乐电针组及氟西汀组,每组12只。孤养结合CUMS21天复制抑郁症模型,通过开野试验观察大鼠行为学变化,采用免疫组织化学法、酶联免疫吸附法及荧光实时定量PCR分别检测TRH在大鼠下丘脑中的表达情况。结果:模型组大鼠开野实验水平运动及垂直运动明显减少,脉冲电针组、音乐电针组及氟西汀组均可改善此变化;模型组大鼠下丘脑内TRH表达均明显降低,脉冲电针组、音乐电针组及氟西汀组可逆转此病理变化,但氟西汀组治疗效果较两组电针治疗效果略胜一筹;两组电针治疗之间无明显统计学差异。结论:抑郁大鼠的TRH含量低于正常;电针治疗抑郁症可能是通过升高TRH的含量而发挥抗抑郁作用。音乐电针与脉冲电针治疗抑郁症效果差异不明显。%Objective:To investigate the influence on the expression of TRH in the hypothalamus of rats with chronic un-predictable mild stress by different electro-acupuncture( EA) treatments, to elucidate the possible role of TRH in the development of experimental depression and the effect of different EA for them.Methods:Adult male SD rats were ran-domly divided into a normal control group(n=12),a model group (n=12),a pulsed EA group(n=12),a music EA group( n=12) and a fluoxetine group( n=12) .Depression models were established by lonely raising and chronic unpre-dictable mild stress for 21 days.Open-field test was performed to test the behavior of rats.The expression of hypothala-mus TRH was detected by using immunohistochemistry , enzyme linked immunosorbent assay( ELISA) and real

  11. 音乐电针和脉冲电针对慢性应激抑郁模型大鼠不同脑区单胺类神经递质表达的影响%Influence of Music Electro-acupuncture and Pulsed Electro-acupuncture on the Different Encephalic Regions of Monoamine Neurotransmitter Chronic Unpredictable Mild Stress Depression Model Rats

    Institute of Scientific and Technical Information of China (English)

    唐银杉; 纪倩; 曹瑾; 滕金艳; 邓晓丰; 李静; 李志刚

    2014-01-01

    目的:对比观察不同电针对慢性应激抑郁模型大鼠额叶和海马5-HT、DA和NE表达的影响,进一步研究音乐电针与脉冲电针干预治疗抑郁症的疗效差异以及其生物学机制。方法:雄性SD大鼠,随机分为5组:正常对照组、模型组、百忧解组、音乐电针组、脉冲电针组,每组10只。除正常对照组外,其余均采用慢性应激结合孤养的方式造模。采用开野实验、糖水消耗实验和体重检测进行各组的行为学评价;采用放射免疫法分别检测大鼠额叶和海马5-HT、DA和NE的表达。结果:实验第21天后,模型组大鼠行为学指标较正常对照组有明显降低(P<0.01);百忧解组、音乐电针组和脉冲电针组与模型组比较,大鼠活动度、糖水消耗量和体重明显升高(P<0.05)。与正常对照组比较,模型组大鼠额叶和海马组织5-HT、DA和NE的表达量明显降低(P<0.01);与模型组相比,百忧解组、脉冲电针组和音乐电针组能提高额叶和海马组织的5-HT、DA、NE的表达量(P<0.05);与脉冲电针组比较,音乐电针组海马和额叶组织的5-HT的表达量有显著性差异(P<0.05)。结论:百忧解、脉冲电针和音乐电针均可改善慢性应激抑郁大鼠的行为学症状,具有一定的抗抑郁作用;音乐电针在提高慢性应激模型大鼠中枢单胺类的神经水平方面优于百忧解和脉冲电针,这可能是音乐电针发挥抗抑郁治疗作用的途径之一。%Objective:To observe the influence of different electro -acupuncture on frontal lobe and hippocampus to 5-HT,DA,NE neurotransmitter ’ s expression of chronic unpredictable mild stress depression model rats , to probe into the mechanism for treating depression .Methods:Fifty male SD rats were randomly divided into five groups:Nor-mal control group, Model group, Fluoxetine group, music electro-acupuncture group and pulsed

  12. 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.

  13. 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

  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. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    OpenAIRE

    Giusti B; Marini M; Rossi L; Lapini I; Magi A; Capalbo A; Lapalombella R; di Tullio S; Samaja M; Esposito F; Margonato V; Boddi M; Abbate R; Velcsteinas A

    2009-01-01

    Abstract: Background: Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after ...

  16. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    OpenAIRE

    Esposito Fabio; Samaja Michele; di Tullio Simona; Lapalombella Rosa; Capalbo Andrea; Magi Alberto; Lapini Ilaria; Rossi Luciana; Marini Marina; Giusti Betti; Margonato Vittoria; Boddi Maria; Abbate Rosanna; Veicsteinas Arsenio

    2009-01-01

    Abstract Background Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after th...

  17. 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

  18. Effect of serotonergic and catecholaminergic antagonists on mild-stress-induced excessive grooming in the rat.

    Science.gov (United States)

    Rodríguez Echandía, E L; Broitman, S T; Fóscolo, M R

    1983-12-01

    Excessive grooming was induced in male rats by two ip injections of physiological saline. This mild stressful procedure did not modify open-field locomotion in 5-min trials. Methysergide (15 mg/kg) and pizotifene (5 mg/kg), serotonergic blockers, selectively prevented the grooming response to saline without affecting locomotion. Haloperidol (.4 mg/kg) also prevented the excessive grooming. However, this dopaminergic blocker impaired locomotion. The alpha- or beta-adrenoceptor antagonists phentolamine (20 mg/kg) and l-propranolol (20 mg/kg) did not prevent the excessive grooming in response to saline and did not affect locomotion. The results suggest that some serotonergic pathways in the brain are involved in the grooming response to a mild stress and support previous findings on the role of dopaminergic systems on this activity.

  19. Treatment of a mild chronic case of ciguatera fish poisoning with intravenous mannitol, a case study.

    Science.gov (United States)

    Mitchell, Gary

    2005-03-01

    This article describes a recent case of ciguatera poisoning treated with intravenous mannitol. Mannitol has been used with good effect in non-controlled studies in acutely severely poisoned patients, but is not described in the treatment of chronic or milder poisoning. Our patient was a 35-year-old Niuean man who had eaten a ciguatoxic fish two weeks previously. His symptoms were not severe but were very unpleasant and restricted his ability to work. He was given a single dose of mannitol (0.66g/kg) as an intravenous infusion over two hours. His symptoms dramatically improved within 24 hours, and within a few days he felt virtually back to his former self. He experienced no side effects to the mannitol. It is suggested that intravenous mannitol may prove to be a useful treatment for mild to moderate ciguatera poisoning, and for patients who present late for treatment.

  20. Cardiac response to exercise in mild-to-moderate chronic obstructive pulmonary disease

    Institute of Scientific and Technical Information of China (English)

    Hao-Yan Wang; Qiu-Fen Xu; Yao Xiao

    2009-01-01

    Objective Chronic obstructive pulmonary disease (COPD) increases the risk of cardiovascular problem.The symptom of dyspnea on exertion may be associated with pulmonary dysfunction or heart failure, or both. The study objective was to determine whether cardiac dysfunction adds to the mechanism of dyspnea caused mainly by impaired lung function in patients with mild-to-moderate COPD. Methods Patients with COPD and healthy controls performed incremental and constant work rate exercise testing. Venous blood samples were collected in 19 COPD patients and 10 controls before and during constant work exercise for analysis of N-terminal-pro-BNP (NT-pro-BNP). Results Peak oxygen uptake and constant work exercise time (CWET) were significantly lower in COPD group than in control group (15.81±3.65 vs 19.19a±6.16 ml/min kg, P=0.035 and 7.78±6.53 rain vs 14.77±7.33 min, P=0.015, respectively). Anaerobic threshold, oxygen pulse and heart rate reserve were not statistically significant between COPD group and control group. The NT-pro-BNP levels both at rest and during constant work exercise were higher in COPD group compared to control group, but without statistical significance. The correlations between CWET and NT-proBNP at rest or during exercise in patients with COPD were not statistically significant. Conclusions Heart failure does not contribute to exercise intolerance in mild-to-moderate COPD.

  1. Association between macular degeneration and mild to moderate chronic kidney disease

    Science.gov (United States)

    Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

    2017-01-01

    Abstract Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264–1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218–1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients. PMID:28296786

  2. Mild and moderate pre-dialysis chronic kidney disease is associated with increased coronary artery calcium

    Directory of Open Access Journals (Sweden)

    Budoff M

    2011-12-01

    Full Text Available Sion K Roy, Albert Cespedes, Dong Li, Tae-Young Choi, Matthew J BudoffDivision of Cardiology, Department of Medicine, Los Angeles Biomedical Research Center at Harbor-UCLA Medical Center, Torrance, California, USABackground: It is increasingly evident that patients with chronic kidney disease (CKD are more likely to die from heart disease than kidney failure. This study evaluated whether pre-dialysis CKD is an independent risk factor for coronary artery calcium (CAC.Methods: A total of 544 consecutive patients who underwent CAC scoring were analyzed. Eleven patients requiring hemodialysis were excluded. Patients were divided into three groups: normal glomerular filtration rate (GFR (GFR > 90 mL/min/1.73 m2, mild CKD (90 ≥ GFR > 60 mL/min/1.73 m2, and moderate CKD (60 ≥ GFR > 30 mL/min/1.73 m2. Continuous and categorical variables were compared using analysis of variance and the χ2 statistic. A multiple logistic regression model was used for detecting the association between total CAC score and GFR. An unadjusted model was used, followed by a second model adjusted for covariates known to be related to CAC. Another multivariable binary logistic model predicting the presence of CAC (>10 was performed and odds of incidence of CAC (>10 were calculated among the three GFR subgroups.Results: After adjustment for covariates, patients with mild CKD had mean CAC scores 175 points higher than those with the referent normal GFR (P = 0.048, while those with moderate CKD had mean CAC scores 693 points higher than the referent (P < 0.001. After adjustment for covariates, patients with mild CKD were found to be 2.2 times more likely (95% confidence interval 1.3–3.7, P = 0.004 and patients with moderate CKD were 6.4 times more likely (95% confidence interval 2.9–14.3, P < 0.001 to have incident CAC compared with the group with normal GFR.Conclusion: Mild and moderate pre-dialysis CKD are independent risk factors for increased mean and incident CAC

  3. The Effects of Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Combined Mild Traumatic Brain Injury/Post-Traumatic Stress Disorder on Returning Veterans.

    Science.gov (United States)

    Combs, Hannah L; Berry, David T R; Pape, Theresa; Babcock-Parziale, Judith; Smith, Bridget; Schleenbaker, Randal; Shandera-Ochsner, Anne; Harp, Jordan P; High, Walter M

    2015-07-01

    United States veterans of the Iraqi (Operation Iraqi Freedom [OIF]) and Afghanistan (Operation Enduring Freedom [OEF]) conflicts have frequently returned from deployment after sustaining mild traumatic brain injury (mTBI) and enduring stressful events resulting in post-traumatic stress disorder (PTSD). A large number of returning service members have been diagnosed with both a history of mTBI and current PTSD. Substantial literature exists on the neuropsychological factors associated with mTBI and PTSD occurring separately; far less research has explored the combined effects of PTSD and mTBI. The current study employed neuropsychological and psychological measures in a sample of 251 OIF/OEF veterans to determine whether participants with a history of mTBI and current PTSD (mTBI+PTSD) have poorer cognitive and psychological outcomes than participants with mTBI only (mTBI-o), PTSD only (PTSD-o), or veteran controls (VC), when groups are comparable on intelligence quotient, education, and age. The mTBI+PTSD group performed more poorly than VC, mTBI-o, and PTSD-o groups on several neuropsychological measures. Effect size comparisons suggest small deleterious effects for mTBI-o on measures of processing speed and visual attention and small effects for PTSD-o on measures of verbal memory, with moderate effects for mTBI+PTSD on the same variables. Additionally, the mTBI+PTSD group was significantly more psychologically distressed than the PTSD-o group, and PTSD-o group was more distressed than VC and mTBI-o groups. These findings suggest that veterans with mTBI+PTSD perform significantly lower on neuropsychological and psychiatric measures than veterans with mTBI-o or PTSD-o. The results also raise the possibility of mild but persisting cognitive changes following mTBI sustained during deployment.

  4. 米邦塔仙人掌果胶对慢性不可预知温和应激小鼠绝望症状的改善作用%Study on the improvement of milpa alta cactus pectin on desperate symptoms in mice exposed to chronic unpreditc able mild stress

    Institute of Scientific and Technical Information of China (English)

    肖同楚; 黄朝明; 杨兴娥; 湛进进; 郭莲军

    2015-01-01

    目的:研究米邦塔仙人掌果胶( MCP)对慢性不可预知温和应激( CUMS)小鼠绝望症状的改善作用。方法雄性昆明种小鼠随机分为空白对照组、模型组、MCP低剂量组(50 mg/kg)、MCP中剂量组(100 mg/kg)、MCP高剂量组(200 mg/kg)。除空白对照组不进行任何应激处理外,其余组均进行CUMS,各MCP组均在进行CUMS期间每天灌胃相应剂量MCP。造模结束24 h后进行悬尾实验,48 h后进行强迫游泳实验。结果模型组悬尾实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP高剂量组潜伏期显著长于模型组(P<0.05),MCP中、高剂量组累计不动时间显著短于模型组(P均<0.01)。模型组强迫游泳实验潜伏期显著短于空白对照组(P<0.01),累计不动时间显著长于空白对照组(P<0.01);MCP各给药组潜伏期与空白对照组比较差异均无统计学意义(P均>0.05),而MCP高剂量组累计不动时间显著短于模型组(P<0.05)。结论 MCP能较好地缓解CMS小鼠的行为绝望症状。%Objetc ive It is to investigate the effect of milpa alta cactus pectin ( MCP) on desperate symptoms in mice ex-posed to chronic unpredictable mild stress ( CUMS) .Methods The male Kunming mice were randomly divided into 5 groups such as control group, CUMS+Vehicle group, CUMS+MCP 50 mg/kg group, CUMS+MCP 100 mg/kg group, and CUMS+MCP 200 mg/kg group.Except the control group, the other groups were exposed to CUMS for 6 weeks.And during this peri-od, the animals were treated with corresponding drug by intragastric administration.While the ends of the model, the tail sus-pension test ( TST) was carried out after 24 hours, and the forced swimming test ( FST) were conducted after 48 hours.Re-sults In TST, the latency of the CUMS+Vehicle group was significantly shorter (P0.05), and the immobility time of the

  5. 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

  6. CUMS抑郁模型大鼠脑组织DA、5-HT及其代谢产物的浓度变化%Concentration change of DA, 5-HT and their metabolites in brain tissue of depression models rat treated with chronic unpredicted mild stress

    Institute of Scientific and Technical Information of China (English)

    唐亚梅; 陈春梅; 刘勇

    2012-01-01

    Objective We explored the related neurobiochemistry pathomechanism by the comparison of concentration of dopamine(DA), 5-hydroxytryptamine (5-HT) and their metabolites in brain tissue in the Chronic unpredicted mild stress (CUMS)depression model rats. Methods 24 male Spragur-Dawley (SD) rats were randomly assigned to 3 groups: control group, model group and fluoxetine group. CUMS with solitary condition was taken to manufacture depression rat model. After separated the brains tissues of CUMS depression rats, the levels of DA, 5-HT and their metabolites of the tissue homogenate from the medial prefrontal cortex (mPFC) and hippocampus were examined with Coularray Electrochemic detection for high performance liquid chromatogram (HPLC) technique. Results Compared to contronl group, the levels of DA, homovanillic acid (HVA), 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) in the mPFC of depression model rats have significantly decreased(P<0.01 or 0.05), and the levels of DA, HVA and 5-HT in hippocampus have significantly decreased (P<0.01 or 0.05); Compared to model group, the levels of DA, HVA and 5 -HT in the mPFC of fluoxetine group rats have significantly increased (P<0.01 or 0.05), and the levels of DA, 5 -HT and 5 -HIAA in hippocampus have significantly increased (P <0.05). Conclusion The activity of DA and 5 -HT systems in the mPFC and hippocampus were decreased in CUMS depression model rats.%目的:通过分析抑郁模型大鼠脑组织DA、5-HT及其代谢产物的浓度变化,探讨抑郁症发病的神经生化机制.方法:将24只雄性SD大鼠随机分成对照组、模型组和氟西汀组3组;采用慢性轻度不可预见性应激(CUMS)结合孤养建立抑郁大鼠模型,随后取脑并分离内侧前额皮质(mPFC)和海马,采用库仑阵列电化学高效液相色谱法测定上述脑区DA、5-HT及其代谢产物的浓度.结果:与对照组比较,模型组大鼠mPFC区DA、高香草酸(HVA)、5-HT及5-羟吲哚乙酸(5-HIAA

  7. The effect of repetitive transcranial magnetic stimulation on the changes of depressive like behaviors in chronic unpredictable mild stress model rats and its possible mechanism%重复经颅磁刺激对抑郁模型大鼠行为的改善作用及机制

    Institute of Scientific and Technical Information of China (English)

    刘高华; 陈冠婕; 陈怡环; 杨帆; 张瑞国; 彭正午; 谭庆荣

    2013-01-01

    Objective To investigate the effect of repetitive transcranial magnetic stimulation (rTMS) on the depressive like behaviors and expression of brain derived neurotrophic factor (BDNF),IL-1β and NF-κB of hippocampal in chronic unpredictable mild stress (CUMS) rats.Methods Thirty-two adult male rats were randomly divided into four groups (n =8):Control group,Control + rTMS group,CUMS group and CUMS + rTMS group.The sucrose preference test,forced swim test and open field test were used to evaluate depressive like behaviors for each groups.In addition,the expression of BDNF,NF-κB and IL-1 β in hippocampal were detected by western blot and ELISA after behavioral test,respectively.Results 1.The effects of rTMS on depressive like behaviors of CUMS rats:in the sucrose preference test,the sucrose preference rate of CUMS rats (0.67 ± 0.06) was significantly lower than Control group (0.91 ± 0.04),which was higher in the CUMS + rTMS group (0.83 ±0.08).In the forced swim test,the immobility time of CUMS group ((26.88 ± 11.33) s) was longer than Control group ((15.22 ± 6.75) s) and CUMS + rTMS group ((18.41 ± 6.95) s).In the open field test,both the total distance travelled and number of central area entry times of CUMS group((849.165 ± 769.01) cm,(7.42 ± 5.68))were significantly shorter ((6224.81 ± 1403.2) cm) and smaller (22.86 ± 3.72) than Control group,and those of the CUMS + rTMS were longer ((4105.57 ± 1516.92)cm) and larger (21.25 ± 3.45).All the behavioral results were statistically significant (P< 0.05).And of all the aforementioned behavioral parameters,there were no significant differences between Control group and Control + rTMS group(P>0.05).2.The effects of rTMS on the hippocampal expressions of BDNF,NF-κB and IL-1β in CUMS rats:compared with Control group,the hippocampal expression of BDNF in CUMS rats was significantly decreased,while the expressions of NF-κB and IL-1β in the hippocampus were significantly increased (P< 0.05).Compared

  8. Association of Mild to Moderate Chronic Kidney Disease With Venous Thromboembolism Pooled Analysis of Five Prospective General Population Cohorts

    NARCIS (Netherlands)

    Mahmoodi, Bakhtawar K.; Gansevoort, Ron T.; Naess, Inger Anne; Lutsey, Pamela L.; Braekkan, Sigrid K.; Veeger, Nic J. G. M.; Brodin, Ellen E.; Meijer, Karina; Sang, Yingying; Matsushita, Kunihiro; Hallan, Stein I.; Hammerstrom, Jens; Cannegieter, Suzanne C.; Astor, Brad C.; Coresh, Josef; Folsom, Aaron R.; Hansen, John-Bjarne; Cushman, Mary

    2012-01-01

    Background-Recent findings suggest that chronic kidney disease (CKD) may be associated with an increased risk of venous thromboembolism (VTE). Given the high prevalence of mild-to-moderate CKD in the general population, in depth analysis of this association is warranted. Methods and Results-We poole

  9. Alterations in magnesium and oxidative status during chronic emotional stress.

    Science.gov (United States)

    Cernak, I; Savic, V; Kotur, J; Prokic, V; Kuljic, B; Grbovic, D; Veljovic, M

    2000-03-01

    Magnesium and oxidative status were investigated in young volunteers exposed to chronic stress (political intolerance, awareness of potential military attacks, permanent stand-by duty and reduced holidays more than 10 years) or subchronic stress consisting of everyday mortal danger in military actions lasting more than 3 months. Significant decreases in plasma ionized Mg2+, total Mg and ionized Ca2+ concentrations were found in both groups. Similarly, both study groups exhibited oxidative stress as assessed by increased plasma superoxide anions and malondialdehyde and modified antioxidant defense. There were no significant differences between the two stress groups. A negative correlation between magnesium balance and oxidative stress was observed suggesting that the same etiological factor (chronic stress) initiate decreases in both free and total magnesium concentrations and simultaneously increase oxidative stress intensity. These findings support the need for magnesium supplementation with antioxidant vitamins for people living in conditions of chronic stress.

  10. 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

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

    Science.gov (United States)

    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.

  12. Filling in the gaps: Anticipatory control of eye movements in chronic mild traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Mithun Diwakar

    2015-01-01

    Full Text Available A barrier in the diagnosis of mild traumatic brain injury (mTBI stems from the lack of measures that are adequately sensitive in detecting mild head injuries. MRI and CT are typically negative in mTBI patients with persistent symptoms of post-concussive syndrome (PCS, and characteristic difficulties in sustaining attention often go undetected on neuropsychological testing, which can be insensitive to momentary lapses in concentration. Conversely, visual tracking strongly depends on sustained attention over time and is impaired in chronic mTBI patients, especially when tracking an occluded target. This finding suggests deficient internal anticipatory control in mTBI, the neural underpinnings of which are poorly understood. The present study investigated the neuronal bases for deficient anticipatory control during visual tracking in 25 chronic mTBI patients with persistent PCS symptoms and 25 healthy control subjects. The task was performed while undergoing magnetoencephalography (MEG, which allowed us to examine whether neural dysfunction associated with anticipatory control deficits was due to altered alpha, beta, and/or gamma activity. Neuropsychological examinations characterized cognition in both groups. During MEG recordings, subjects tracked a predictably moving target that was either continuously visible or randomly occluded (gap condition. MEG source-imaging analyses tested for group differences in alpha, beta, and gamma frequency bands. The results showed executive functioning, information processing speed, and verbal memory deficits in the mTBI group. Visual tracking was impaired in the mTBI group only in the gap condition. Patients showed greater error than controls before and during target occlusion, and were slower to resynchronize with the target when it reappeared. Impaired tracking concurred with abnormal beta activity, which was suppressed in the parietal cortex, especially the right hemisphere, and enhanced in left caudate and

  13. Chronic administration of quercetin prevent spatial learning and memory deficits provoked by chronic stress in rats.

    Science.gov (United States)

    Mohammadi, Hadis Said; Goudarzi, Iran; Lashkarbolouki, Taghi; Abrari, Kataneh; Elahdadi Salmani, Mahmoud

    2014-08-15

    There are several reports that cognitive impairment is observed in stress related disorders and chronic stress impairs learning and memory. However, very few studies have looked into the possible ways of preventing this stress-induced deficit. This research study was conducted to evaluate the effects of quercetin, a natural flavonoid, with strong antioxidant and free radical scavenger properties, on chronic stress induced learning and memory deficits and oxidative stress in hippocampus. For chronic stress, rats were restrained daily for 6h/day (from 9:00 to 15:00) for 21 days in well-ventilated plexiglass tubes without access to food and water. The animals were injected with quercetin or vehicle 60 min before restraint stress over a period of 21 days. Then, rats trained with six trials per day for 6 consecutive days in the water maze. On day 28, a probe test was done to measure memory retention. In addition, oxidative stress markers in the hippocampus were evaluated. Results of this study demonstrated that chronic stress exposure rats exhibited higher escape latency during training trials and reduced time spent in target quadrant, higher escape location latency and average proximity in probe trial test. Quercetin (50mg/kg) treatment during restraint stress (21 days) markedly decreased escape latency and increased time spent in target quadrant during Morris water maze task. In comparison to vehicle treated group, chronic-stress group had significantly higher malondialdehyde (MDA) levels, significantly higher superoxide dismutase (SOD) activity and significantly lower glutathione peroxidase (GPx) activity in the hippocampus. Quercetin treatment caused a significant decrease in the hippocampus MDA levels and improves SOD and GPx activities in stressed animals. Finally, quercetin significantly decreased plasma corticosterone levels in stressed animals. Based on results of this study, chronic stress has detrimental effects on learning and memory and quercetin treatment

  14. Influence of Perceived Stress on Incident Amnestic Mild Cognitive Impairment: Results From the Einstein Aging Study.

    Science.gov (United States)

    Katz, Mindy J; Derby, Carol A; Wang, Cuiling; Sliwinski, Martin J; Ezzati, Ali; Zimmerman, Molly E; Zwerling, Jessica L; Lipton, Richard B

    2016-01-01

    Stress is a potentially remediable risk factor for amnestic mild cognitive impairment (aMCI). Our objective is to determine whether perceived stress predicts incident aMCI and to determine if the influence of stress on aMCI is independent of known aMCI risk factors, particularly demographic variables, depression, and apolipoprotein genotype. The Einstein Aging Study is a longitudinal community-based study of older adults. The Perceived Stress Scale (PSS) was administered annually in the Einstein Aging Study to participants (N=507; 71 developed incident aMCI; mean follow-up time=3.6 y, SD=2.0) who were aged 70 years and older, free of aMCI and dementia at baseline PSS administration, and had at least 1 subsequent annual follow-up. Cox hazard models were used to examine time to aMCI onset adjusting for covariates. High levels of perceived stress are associated with a 30% greater risk of incident aMCI (per 5-point increase in PSS: hazard ratio=1.30; 95% confidence interval, 1.08-1.58) independent of covariates. The consistency of results after covariate adjustment and the lack of evidence for reverse causation in longitudinal analyses suggest that these findings are robust. Understanding of the effect of perceived stress on cognition may lead to intervention strategies that prevent the onset of aMCI and Alzheimer dementia.

  15. Common biochemical defects linkage between post-traumatic stress disorders, mild traumatic brain injury (TBI) and penetrating TBI.

    Science.gov (United States)

    Prasad, Kedar N; Bondy, Stephen C

    2015-03-02

    Post-traumatic stress disorder (PTSD) is a complex mental disorder with psychological and emotional components, caused by exposure to single or repeated extreme traumatic events found in war, terrorist attacks, natural or man-caused disasters, and by violent personal assaults and accidents. Mild traumatic brain injury (TBI) occurs when the brain is violently rocked back and forth within the skull following a blow to the head or neck as in contact sports, or when in close proximity to a blast pressure wave following detonation of explosives in the battlefield. Penetrating TBI occurs when an object penetrates the skull and damages the brain, and is caused by vehicle crashes, gunshot wound to the head, and exposure to solid fragments in the proximity of explosions, and other combat-related head injuries. Despite clinical studies and improved understanding of the mechanisms of cellular damage, prevention and treatment strategies for patients with PTSD and TBI remain unsatisfactory. To develop an improved plan for treating and impeding progression of PTSD and TBI, it is important to identify underlying biochemical changes that may play key role in the initiation and progression of these disorders. This review identifies three common biochemical events, namely oxidative stress, chronic inflammation and excitotoxicity that participate in the initiation and progression of these conditions. While these features are separately discussed, in many instances, they overlap. This review also addresses the goal of developing novel treatments and drug regimens, aimed at combating this triad of events common to, and underlying, injury to the brain.

  16. Total Flavonoids Extracted from Xiaobuxin-Tang on the Hyperactivity of Hypothalamic-Pituitary-Adrenal Axis in Chronically Stressed Rats

    Directory of Open Access Journals (Sweden)

    Lei An

    2011-01-01

    Full Text Available Our previous studies have demonstrated that the total flavonoids (XBXT-2 isolated from the extract of Xiaobuxin-Tang (XBXT, a traditional Chinese herbal decoction, ameliorated behavioral alterations and hippocampal dysfunctions in chronically stressed rats. Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA axis is one of the most consistent findings in stress-related depression. Herein, we used the same chronic mild stress model of rats as before to further investigate the effect of XBXT-2 on the hyperactivity of HPA axis, including the stress hormones levels and glucocorticoid receptors (GRs expression. Our ELISA results showed that chronic administration of XBXT-2 (25, 50 mg kg−1, p.o., 28 days, the effective doses for behavioral responses significantly decreased serum corticosterone level and its upstream stress hormone adrenocorticotropic hormone (ACTH level in chronically stressed rats. Furthermore, western blotting result demonstrated XBXT-2 treatment ameliorated stress-induced decrease of GRs expression in hippocampus, an important target involved in the hyperactivity of HPA axis. These results were similar to that of classic antidepressant imipramine treatment (10 mg kg−1, p.o.. In conclusion, the modulation of HPA axis produced by XBXT-2, including the inhibition of stress hormones levels and up-regulation of hippocampal GRs expression, may be an important mechanism underlying its antidepressant-like effect in chronically stressed rats.

  17. The effect of chronic mild hyponatremia on bone mineral loss evaluated by retrospective national Danish patient data

    DEFF Research Database (Denmark)

    Kruse, Christian; Eiken, Pia; Verbalis, Joseph;

    2016-01-01

    PURPOSE: To evaluate the effect of chronic mild hyponatremia ([Na+]=130-137mmol/L) on bone mineral content (BMC) and bone mineral density (BMD) loss through multiple, serial dual-energy X-ray absorptiometry (DXA) scans. METHODS: Utilizing biochemical and DXA scan data from two Danish regions...... between 2004 and 2011, supplemented with national Danish patient diagnosis and prescription reimbursement databases, a retrospective cohort study was performed. All subjects with more than one DXA scan were included, then stratified into "normonatremia" ([Na(+)]=[137.00-147.00] mmol/L) and "mild...

  18. Arterial stiffness and enlargement in mild-to-moderate chronic kidney disease.

    Science.gov (United States)

    Briet, M; Bozec, E; Laurent, S; Fassot, C; London, G M; Jacquot, C; Froissart, M; Houillier, P; Boutouyrie, P

    2006-01-01

    Chronic kidney disease (CKD) is associated with an increased risk of cardiovascular morbidity and mortality. Arterial stiffness and remodeling have been well documented in patients with end-stage renal disease, but little is known about arterial phenotype in CKD patients with moderate reduction in glomerular filtration rate (GFR). In total, 95 patients (58+/-15 years, mean+/-s.d.) with CKD and GFR measured by renal clearance of (51)Cr-ethylenediaminetetraacetate were compared to 121 hypertensive patients without CKD (59+/-11 years), and 57 normotensive subjects (56+/-6 years). Common carotid artery diameter, intima-media thickness (IMT), distensibility, and Young's elastic modulus were noninvasively determined with a high-definition echotracking system. Patients with CKD had a significantly larger carotid internal diameter than in hypertensives and normotensives (6.32+/-1.05, 5.84+/-0.74, and 5.50+/-0.64 m x 10(-3), respectively; Pelastic modulus did not significantly differ between CKD and hypertensives; normotensives had significantly higher distensibility and lower elastic modulus than CKD and hypertensive patients. Carotid-femoral pulse wave velocity was significantly higher in CKD patients than in hypertensives and normotensives. In multivariate analyses either involving the entire population or restricted to CKD patients, GFR was independently and strongly related to carotid diameter and elastic modulus. Arterial enlargement and increased arterial stiffness occur in parallel with the decline in renal function in patients with mild-to-moderate CKD.

  19. Effect of mild aerobic training on the myocardium of mice with chronic Chagas disease

    Directory of Open Access Journals (Sweden)

    Preto E

    2015-09-01

    Full Text Available Emerson Preto,1 Nathalia EA Lima,1 Lucila Simardi,2 Fernando Luiz Affonso Fonseca,2,3 Abílio Augusto Fragata Filho,4 Laura Beatriz Mesiano Maifrino1,41Universidade São Judas Tadeu, São Paulo, 2Faculdade de Medicina do ABC, Santo André, 3Universidade Federal de São Paulo, Diadema, 4Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, BrazilBackground: Chronic chagasic heart disease represents extensive remodeling of the cardiovascular system, manifested as cardiac denervation, interstitial mononuclear infiltrate, myocyte and vascular degenerative changes, fibrosis, and hypertrophy. Moreover, aerobic exercises are widely indicated for the treatment of various disorders of the cardiovascular system.Purpose: To evaluate the right and left ventricles of BALB/c mice with chronic Chagas disease, undergoing mild exercise, by using morphometric and stereological methods.Materials and methods: A total of 20 male mice at 4 months of age were used for experiments. The animals were divided into four groups (n=5 in each group: untrained control, trained control, untrained infected (UI, and trained infected (TI. Animals of UI and TI groups were inoculated with 1,000 trypomastigote forms of Trypanosoma cruzi (Y strain, and after 40 days, animals entered chronic phase of the disease. Physical exercise, which included swimming, was performed for 30 minutes daily, five times a week for 8 consecutive weeks at a bath temperature of 30°C. After the trial period, euthanasia and subsequent withdrawal of the heart were done. The organ was prepared by histological staining procedures with hematoxylin–eosin and picrosirius red.Results: We found that the physical training used in our experimental model promoted increase in volume density of capillaries and decrease in volume density of collagen fibers and cross-sectional area of cardiomyocytes in chagasic animals (TI group. By histopathological analysis, we found differences in the inflammatory infiltrate

  20. Postconcussive symptoms and posttraumatic stress disorder after mild traumatic brain injury.

    Science.gov (United States)

    Bryant, R A; Harvey, A G

    1999-05-01

    Postconcussive symptoms after mild traumatic brain injury (MTBI) may be exacerbated by anxiety associated with posttraumatic stress. The aim of this study was to investigate the relationship between postconcussive symptoms and posttraumatic stress disorder (PTSD) in an MTBI population. Survivors of motor vehicle accidents who either sustained an MTBI (N = 46) or no TBI (N = 59) were assessed 6 months posttrauma for PTSD and postconcussive symptoms. Postconcussive symptoms were more evident in MTBI patients with PTSD than those without PTSD, and in MTBI patients than non-TBI patients. Further, postconcussive symptoms were significantly correlated with PTSD symptoms. These findings indicate that postconcussive symptoms may be mediated by an interaction of neurological and psychological factors after MTBI.

  1. Possible Biomarkers of Chronic Stress Induced Exhaustion - A Longitudinal Study.

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    Johanna Wallensten

    Full Text Available Vascular endothelial growth factor (VEGF, epidermal growth factor (EGF and monocyte chemotactic protein-1 (MCP-1 have previously been suggested to be potential biomarkers for chronic stress induced exhaustion. The knowledge about VEGF has increased during the last decades and supports the contention that VEGF plays an important role in stress and depression. There is scarce knowledge on the possible relationship of EGF and MCP-1 in chronic stress and depression. This study further examines the role of VEGF, EGF and MCP-1 in women with chronic stress induced exhaustion and healthy women during a follow-up period of two years.Blood samples were collected from 105 women with chronic stress induced exhaustion on at least 50% sick leave for at least three months, at inclusion (T0, after 12 months (T12 and after 24 months (T24. Blood samples were collected at inclusion (T0 in 116 physically and psychiatrically healthy women. The plasma levels of VEGF, EGF and MCP-1 were analyzed using Biochip Array Technology. Women with chronic stress induced exhaustion had significantly higher plasma levels of VEGF and EGF compared to healthy women at baseline, T12 and at T24. There was no significant difference in plasma levels of MCP-1. Plasma levels of VEGF and EGF decreased significantly in women with chronic stress induced exhaustion during the two years follow-up.The replicated findings of elevated levels of VEGF and EGF in women with chronic stress induced exhaustion and decreasing plasma levels of VEGF and EGF during the two years follow-up add important knowledge to the pathophysiology of chronic stress induced exhaustion.

  2. Differential translocation of heat shock factor-1 after mild and severe stress to human skin fibroblasts undergoing aging in vitro.

    Science.gov (United States)

    Demirovic, Dino; de Toda, Irene Martinez; Nizard, Carine; Rattan, Suresh I S

    2014-12-01

    Repeated exposure to mild heat shock (HS) has been shown to induce a wide range of health promoting hormetic effects in various biological systems, including human cells undergoing aging in vitro. In order to understand how cells distinguish between mild and severe stress, we have investigated the extent of early and immediate HS response by analyzing the nuclear translocation of the transcription factor heat shock factor-1 (HSF1), in serially passaged normal adult human facial skin fibroblasts exposed to mild (41 °C) or severe (43 °C) HS. Cells respond differently when exposed to mild and severe HS at different passage levels in terms of the extent of HSF1 translocation. In early passage young cells there was a 5-fold difference between mild and severe HS in the extent of HSF1 translocation. However, in near senescent late passage cells, the difference between mild and severe stress in terms of the extent of HSF1 translocation was reduced to less than 2-fold. One of the reasons for this age-related attenuation of heat shock response is due to the fact there was a higher basal level of HSF1 in the nuclei of late passage cells, which is indicative of increased intrinsic stress during cellular aging. These observations are consistent with previously reported data that whereas repeated mild stress given at younger ages can slow down aging and increase the lifespan, the same level of stress given at older ages may not provide the same benefits. Therefore, elucidating the early and immediate steps in the induction of stress response can be useful in deciding whether a particular level of stress is potentially hormetically beneficial or not.

  3. Comparison of Depression, Anxiety, and Stress Between Mild and Severe Non-cardiac Chest Pain

    Directory of Open Access Journals (Sweden)

    Bahremand

    2016-05-01

    Full Text Available Background Physical and psychological factors affect one another in patients presenting with non-cardiac chest pain. Studying the psychological components of these patients may improve their treatment process. Objectives To compare depression, anxiety, and stress severity between mild and severe chest pain in patients with non-cardiac chest pain. Patients and Methods A cross-sectional design was used. The statistical population comprised patients with non-cardiac chest pain admitted to the Heart Emergency Center in Kermanshah, Iran. Using a matching method, 94 participants with mild and severe non-cardiac chest pain were selected and studied in two groups of 47. The instruments used in this study include the Comorbidity Index, the brief pain index (BPI, and the depression, anxiety, and stress scale (DASS. The multivariate analysis of variance, chi-squared test, and t-test were used for data analysis. Results After adjusting for the effects of age and comorbid conditions, results showed that there was a significant difference between the two groups in terms of depression, anxiety, and stress; the severity of these variables was exacerbated in patients with severe chest pain (P < 0.001. Conclusions Depression, anxiety, and stress are common psychological components in patients with non-cardiac chest pain especially those with severe chest pain and it is essential that health professionals pay attention to these factors. Therefore, paying attention to psychological factors could help experts to choose solutions that will decrease pain and side effects of the diseases. It may also facilitate treatment procedures among patients in severe pain. Further investigation to determine the association between these variables and non-cardiac chest pain should be considered.

  4. 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.

  5. Mild heat stress at a young age in Drosophila melanogaster leads to increased Hsp70 synthesis after stress exposure later in life

    Indian Academy of Sciences (India)

    Torsten Nygaard Kristensen; Jesper Givskov Sørensen; Volker Loeschcke

    2003-12-01

    In a number of animal species it has been shown that exposure to low levels of stress at a young age has a positive effect on stress resistance later in life, and on longevity. The positive effects have been attributed to the activation of defence/cleaning systems (heat shock proteins (Hsps), antioxidases, DNA repair) or to effects of a changed metabolic rate, or both. We investigated the effect of mild stress exposures early in life on Hsp70 synthesis after a harder stress exposure later in life in five isofemale lines of Drosophila melanogaster. Female flies were either exposed to repeated bouts of mild heat stress (3 h at 34°C) at a young age (days 2, 4 and 6 post-eclosion) or held under standard laboratory conditions. At 16 and 32 days of adult age, respectively, flies were exposed to a high temperature treatment known to induce Hsp70 in the investigated species (1 h at 37°ºC). Thereafter, the inducible Hsp70 levels were measured. Our data show a tendency towards increased Hsp70 synthesis with increased age for both ‘mild stress’ and ‘no stress’ flies. Moreover, the results show that flies exposed to mild stress at a young age synthesized more Hsp70 upon induction, compared to control flies, and that this difference was accentuated at 32 days compared to 16 days of age. Thus, bouts of mild heat stress at a young age impact on the physiological stress response system later in life. This may be caused by an increased ability to react to future stresses. Alternatively, the mild stress exposure at a young age may actually have caused cellular damages increasing the need for Hsp70 levels after stress exposure later in life. The importance of an Hsp70 upregulation (throughout life) in explaining the phenomenon of hormesis is discussed, together with alternative hypotheses, and suggestions for further studies.

  6. 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.

  7. Hyperbaric Oxygen Therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury PCS and PTSD

    Science.gov (United States)

    2015-10-01

    Award Number: W81XWH-10-1-0962 TITLE: Hyperbaric Oxygen therapy in the Treatment of Chronic Mild-Moderate Blast-Induced Traumatic Brain Injury...Annual 3. DATES COVERED (From – To) 30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-10-1-0962 Hyperbaric Oxygen therapy in...post- hyperbaric oxygen treatment. Four additional subjects have been screened in October 2015 and nine are awaiting first appointment for

  8. Chronic oxidative stress after irradiation: an unproven hypothesis

    Science.gov (United States)

    Cohen, Samuel R; Cohen, Eric P

    2012-01-01

    Injury and organ failure after irradiation of late-responding tissues is a substantial problem in radiation oncology and a major threat after accidental or belligerent exposures. The mechanisms of injury may include death of clonogens, vascular injury, activation of cytokine networks, and/or chronic oxidative stress. Knowledge of mechanisms may guide optimal use of mitigators. The hypothesis of chronic oxidative stress as a mechanism of late radiation injury has received much attention. We review herein the published evidence for chronic oxidative stress in vivo, and for use of antioxidants as mitigators of normal tissue radiation injury. We conclude that there is only indirect evidence for chronic oxidative stress after irradiation, and there are only limited published reports of mitigation by antioxidants. We did not find a differentiation of persistent markers of oxidative stress from an ongoing production of oxygen radicals. It is thus unproven that chronic oxidative stress plays a major role in causing radiation injury and organ failure in late-responding tissues. Further investigation is justified, to identify persistent oxidative stress and to identify optimal mitigators of radiation injury. PMID:23245910

  9. Blast exposure induces post-traumatic stress disorder-related traits in a rat model of mild traumatic brain injury.

    Science.gov (United States)

    Elder, Gregory A; Dorr, Nathan P; De Gasperi, Rita; Gama Sosa, Miguel A; Shaughness, Michael C; Maudlin-Jeronimo, Eric; Hall, Aaron A; McCarron, Richard M; Ahlers, Stephen T

    2012-11-01

    Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety of PTSD-related behavioral traits that were present many months after the blast exposure, including increased anxiety, enhanced contextual fear conditioning, and an altered response in a predator scent assay. We also found elevation in the amygdala of the protein stathmin 1, which is known to influence the generation of fear responses. Because the blast overpressure injuries occurred while animals were under general anesthesia, our results suggest that a blast-related mTBI exposure can, in the absence of any psychological stressor, induce PTSD-related traits that are chronic and persistent. These studies have implications for understanding the relationship of PTSD to mTBI in the population of veterans returning from the wars in Iraq and Afghanistan.

  10. Effect on the Expression of IL-1β,IL-6 in Hippocampus and Serum of Depressive Rats with Chronic Unpredictable Mild Stress Treated by Different Electro-acupuncture Treatment%不同电针对慢性应激抑郁模型大鼠海马及血清细胞因子 IL-1β、IL-6表达的影响

    Institute of Scientific and Technical Information of China (English)

    莫雨平; 李志刚; 邓晓丰; 纪倩; 滕金艳; 姚海江; 宋洪涛; 唐银杉; 许安萍; 张淑静

    2014-01-01

    Objective:To investigate the effect on the expression of IL -1β, IL-6 in the hippocampus and ser-um of rats with chronic unpredictable mild stress treated by different electro -acupuncture(EA) treatment, to elucidate the possible role of IL -1β, IL-6 in the development of experimental depression and the effect of different EA for them .Methods:Adult male SD rats were randomly divided into normal control group ( n=12 ) , model group ( n=12 ) , pulsed EA group ( n=12 ) , music EA group ( n=12 ) and fluoxetine group ( n=12 ) . Depressive models were established by lonely raising and chronic unpredictable mild stress for 21 days. Open-field test was performed to test the behavior of rats .The expression of hippocampus and serum IL -1β, IL-6 was detected by using immunohistochemistry and enzyme linked immunosorbent assay ( ELISA ) techniques respectively .Results:The cross and rear score of model group was significantly lower than that in normal control group , while pulsed EA group , music EA group and fluoxetine group could reverse it .The ex-pression of hippocampus and serum IL -1β, IL-6 in model group increased significantly .The three kinds of treatment could improve these pathological change , but there was no difference among these effects of treat-ment .Conclusion:The levels of IL-1β, IL-6 in hippocampus and serum of depressive rats are higher than those in the normal group .EA treatment may have antagonism against depression by lowering the levels of IL-1β, IL-6 in hippocampus and serum ,and there is no difference between the effects of pulsed EA treat-ment and music EA treatment for depression .%目的:观察不同电针对慢性应激抑郁模型( chronic unpredictable mild stress ,CUMS)大鼠海马及血清中细胞因子IL-1β、IL-6表达的影响,探讨IL-1β、IL-6在大鼠实验性抑郁症发病过程中的作用机制及不同电针干预对其影响。方法:将雄性清洁健康级SD大鼠60只,随机分为正常组、模型组

  11. Web-based support for daily functioning of people with mild intellectual disabilities or chronic psychiatric disorders: A feasibility study in routine practice

    Directory of Open Access Journals (Sweden)

    Jessica de Wit

    2015-05-01

    Conclusion: The initial results of the use of web-based support for this client population seem promising and justify further research on online support for clients with mild intellectual disabilities or chronic psychiatric disorders.

  12. Adult Neurogenesis, Chronic Stress and Depression

    NARCIS (Netherlands)

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

    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

  13. Homoarginine and progression of chronic kidney disease: results from the Mild to Moderate Kidney Disease Study.

    Directory of Open Access Journals (Sweden)

    Christiane Drechsler

    Full Text Available BACKGROUND: Homoarginine is an amino acid derivative mainly synthesized in the kidney. It is suggested to increase nitric oxide availability, enhance endothelial function and to protect against cardiovascular diseases. We aimed to investigate the relation between homoarginine, kidney function and progression of chronic kidney disease (CKD. METHODS: We measured plasma homoarginine concentrations in baseline samples of the Mild to Moderate Kidney Disease (MMKD Study, a prospective cohort study of 227 patients with CKD in Europe. Homoarginine concentrations were available in 182 of the baseline samples and in 139 of the prospectively-followed patients. We correlated homoarginine concentrations to parameters of kidney function. The association between homoarginine and progression of CKD was assessed during a follow-up of up to seven years (median 4.45 years, interquartile range 2.54-5.19 using Cox regression analysis. Progression of CKD was defined as doubling of baseline serum creatinine and/or end-stage renal disease. RESULTS: Study participants were at baseline on average 47±13 years old and 65% were male. Mean±standard deviation of homoarginine concentrations were 2.5±1.1 µmol/L and concentrations were incrementally lower at lower levels of GFR with mean concentrations of 2.90±1.02 µmol/L (GFR>90 ml/min, 2.64±1.06 µmol/L (GFR 60-90 ml/min, 2.52±1.24 µmol/L (GFR 30-60 ml/min and 2.05±0.78 µmol/L (GFR<30 ml/min, respectively (p = 0.002. The age- and sex-adjusted risk to reach the renal endpoint was significantly higher by 62% with each decrease by one standard deviation (1.1 µmol/L of homoarginine (HR 1.62, 95% CI 1.16-2.27, p = 0.005. This association was independent of proteinuria (HR 1.56, 95% CI 1.11-2.20, p = 0.01, and was slightly attenuated when adjusting for GFR (HR 1.40 (95% CI 0.98-1.98, p = 0.06. CONCLUSIONS: Homoarginine concentrations are directly correlated with kidney function and are significantly

  14. 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

  15. 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.

  16. Mild heat stress enhances differentiation and proliferation of Japanese quail myoblasts and enhances slow muscle fiber characteristics.

    Science.gov (United States)

    Choi, Y M; Chen, P R; Shin, S; Zhang, J; Hwang, S; Lee, K

    2016-08-01

    The objective of this study was to investigate the effect of mild heat stress on muscle fiber hyperplastic and hypertrophic growth in quail primary myogenic cells to better understand the mechanisms leading to increased skeletal muscle development in avian embryos incubated at a higher temperature. Compared to control cultures maintained at 37°C, incubation at 39°C enhanced myotube length (P fusion index (56.7 vs. 46.2%, P heat stress compared to the control cells. On the other hand, mild heat stress enhanced protein levels of slow myosin heavy chain isoform (P heat stress plays a significant role in myogenic mechanisms related to muscle mass and development.

  17. [Oxidative stress and antioxitant therapy of chronic periodontitis].

    Science.gov (United States)

    Shen, Y X; Guo, S J; Wu, Y F

    2016-07-01

    Chronic periodontitis is a progressive, infectious inflammation disease, caused by the dysbiosis of oral resident flora, leading to the destruction of periodontium. The onset of pathogenic microorganisms is the etiological factor of periodontitis, while the immuno-inflammatory response affects the progression of the disease. Under chronic periodontitis, oxidative stress occurs when excessive reactive oxygen species are produced and exceed the compensative capacity of the organism. Oxidative stress leads to the destruction of periodontium, in a direct way(damaging the biomolecule) or an indirect way(enhancing the produce of inflammatory cytokine and destructive enzymes). Therefore, as the antagonist of the reactive oxygen species, antioxidants may be helpful to treat the chronic periodontitis. This paper reviewed relevant literatures about the destructive role of excessive reactive oxygen species and protective role of antioxidants in chronic periodontitis.

  18. Chronic unpredictable stress during adolescence causes long-term anxiety.

    Science.gov (United States)

    Chaby, L E; Cavigelli, S A; Hirrlinger, A M; Caruso, M J; Braithwaite, V A

    2015-02-01

    Exposure to stress during adolescence can cause long-term changes in behavior and cognition. Anxiety diagnoses rise during adolescence and are increased by adverse experiences. Currently, it is unknown how long stress during adolescence alters anxiety in adulthood. We found that rats exposed to chronic unpredictable stress during adolescence expressed altered behavior 6.5 months later; showing increased anxiety in a feeding test in a novel environment. Although behavioral changes indicative of anxiety were detected in late adulthood, the basal levels of fecal corticoid metabolites in prior-stressed rats did not differ from unstressed, control rats.

  19. β-Thalassemia and Polycythemia vera: targeting chronic stress erythropoiesis.

    Science.gov (United States)

    Crielaard, Bart J; Rivella, Stefano

    2014-06-01

    β-Thalassemia and Polycythemia vera are genetic disorders which affect the synthesis of red blood cells, also referred to as erythropoiesis. Although essentially different in clinical presentation - patients with β-thalassemia have an impairment in β-globin synthesis leading to defective erythrocytes and anemia, while patients with Polycythemia vera present with high hemoglobin levels because of excessive red blood cell synthesis - both pathologies may characterized by lasting high erythropoietic activity, i.e. chronic stress erythropoiesis. In both diseases, therapeutic strategies targeting chronic stress erythropoiesis may improve the address phenotype and prevent secondary pathology, such as iron overload. The current review will address the basic concepts of these strategies to reduce chronic stress erythropoiesis, which may have significant clinical implications in the near future.

  20. SMFM Statement: benefit of antihypertensive therapy for mild-to-moderate chronic hypertension during pregnancy remains uncertain.

    Science.gov (United States)

    2015-07-01

    Chronic hypertension is present in up to 5% of pregnant women and constitutes a major cause of maternal and neonatal morbidity and mortality. The purpose of this document is to summarize the current recommendations regarding use of antihypertensive medications during pregnancy for women with mild-to-moderate chronic hypertension in the setting of the recently published Control of Hypertension in Pregnancy Study (CHIPS). The recently published CHIPS trial was a multicenter international randomized controlled trial comparing "less tight control" to "tight control" of blood pressure for pregnant women with hypertension. The most updated recommendations regarding management of pregnant women with hypertension are found from the American Congress of Obstetricians and Gynecologists Task Force on Hypertension in Pregnancy, which are endorsed by the Society of Maternal-Fetal Medicine (SMFM). SMFM recommends that clinicians continue to follow existing guidelines for management of pregnant women with mild-to-moderate chronic hypertension due to the fact that the benefits and risks of pharmacologic treatment for these women remain uncertain, and adequately powered randomized controlled trials are needed to address the less common but clinically significant nonsurrogate perinatal outcomes.

  1. Quantification of the impact of single and multiple mild stresses on outgrowth heterogeneity of Bacillus cereus spores

    NARCIS (Netherlands)

    Melis, van C.C.J.; Besten, den H.M.W.; Nierop Groot, M.N.; Abee, T.

    2014-01-01

    Outgrowth heterogeneity of bacterial spore populations complicates both prediction and efficient control of spore outgrowth. In this study, the impact of mild preservation stresses on outgrowth of Bacillus cereus ATCC 14579 spores was quantified during the first stages of outgrowth. Heterogeneity in

  2. 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.

  3. Decreased hepatic contents of coenzyme A molecular species in mice after subchronic mild social defeat stress.

    Science.gov (United States)

    Kubota, Yoshifumi; Goto, Tatsuhiko; Hagiya, Yuki; Chohnan, Shigeru; Toyoda, Atsushi

    2016-01-01

    Social stress may precipitate psychiatric disorders such as depression, which is related to the occurrence of the metabolic syndrome, including obesity and type 2 diabetes. We have evaluated the effects of social stress on central and peripheral metabolism using a model of depression in mice. In the present study, we focused on coenzyme A (CoA) molecular species [i.e. non-esterified CoA (CoASH), acetyl-CoA and malonyl-CoA] which play important roles in numerous metabolic pathways, and we analyzed changes in expression of these molecules in the hypothalamus and liver of adult male mice (C57BL/6J) subjected to 10 days of subchronic mild social defeat stress (sCSDS) with ICR mice as aggressors. Mice (n = 12) exposed to showed hyperphagia- and polydipsia-like symptoms and increased body weight gain compared with control mice which were not affected by exposure to ICR mice (n = 12). To elucidate the underlying metabolic features in the sCSDS model, acetyl-CoA, malonyl-CoA and CoASH tissue levels were analyzed using the acyl-CoA cycling method. The levels of hypothalamic malonyl-CoA, which decreases feeding behavior, were not influenced by sCSDS. However, sCSDS reduced levels of acetyl-CoA, malonyl-CoA and total CoA (sum of the three CoA molecular species) in the liver. Hence, hyperphagia-like symptoms in sCSDS mice evidently occurred independently of hypothalamic malonyl-CoA, but might consequently lead to down-regulation of hepatic CoA via altered expression of nudix hydrolase 7. Future studies should investigate the molecular mechanism(s) underlying the down-regulation of liver CoA pools in sCSDS mice.

  4. 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.

  5. Do epigenetic events take place in the vastus lateralis of patients with mild chronic obstructive pulmonary disease?

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    Ester Puig-Vilanova

    Full Text Available Muscle dysfunction is a major comorbidity in Chronic Obstructive Pulmonary Disease (COPD. Several biological mechanisms including epigenetic events regulate muscle mass and function in models of muscle atrophy. Investigations conducted so far have focused on the elucidation of biological mechanisms involved in muscle dysfunction in advanced COPD. We assessed whether the epigenetic profile may be altered in the vastus lateralis of patients with mild COPD, normal body composition, and mildly impaired muscle function and exercise capacity. In vastus lateralis (VL of mild COPD patients with well-preserved body composition and in healthy age-matched controls, expression of DNA methylation, muscle-enriched microRNAs, histone acetyltransferases (HTAs and deacetylases (HDACs, protein acetylation, small ubiquitin-related modifier (SUMO ligases, and muscle structure were explored. All subjects were clinically evaluated. Compared to healthy controls, in the VL of mild COPD patients, muscle function and exercise capacity were moderately reduced, DNA methylation levels did not differ, miR-1 expression levels were increased and positively correlated with both forced expiratory volume in one second (FEV1 and quadriceps force, HDAC4 protein levels were increased, and muscle fiber types and sizes were not different. Moderate skeletal muscle dysfunction is a relevant feature in patients with mild COPD and preserved body composition. Several epigenetic events are differentially expressed in the limb muscles of these patients, probably as an attempt to counterbalance the underlying mechanisms that alter muscle function and mass. The study of patients at early stages of their disease is of interest as they are a target for timely therapeutic interventions that may slow down the course of the disease and prevent the deleterious effects of major comorbidities.

  6. [Long-term effect of inhaled budesonide in patients with mild to moderate chronic obstructive lung disease. The Osterbro Study].

    Science.gov (United States)

    Vestbo, J; Sørensen, T; Lange, P; Brix, A; Torre, P; Viskum, K

    2000-01-24

    We compared the effect of inhaled budesonide with placebo on decline in lung function and respiratory symptoms in a three-year study of patients with chronic obstructive pulmonary disease (COPD). We used a parallel-group, randomized, double-blind, placebo-controlled design, nested in an ongoing epidemiological survey. Patients were non-asthmatic subjects with a decreased ratio between forced expiratory volume in one second (FEV1) and vital capacity (VC); i.e., FEV1/VC longterm inhaled corticosteroids in the treatment of mild-moderate COPD.

  7. Actual Therapeutic Indication of an Old Drug: Urea for Treatment of Severely Symptomatic and Mild Chronic Hyponatremia Related to SIADH

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    Guy Decaux

    2014-09-01

    Full Text Available Oral urea has been used in the past to treat various diseases like gastric ulcers, liver metastases, sickle cell disease, heart failure, brain oedema, glaucoma, Meniere disease, etc. We have demonstrated for years, the efficacy of urea to treat euvolemic (SIADH or hypervolemic hyponatremia. We briefly describe the indications of urea use in symptomatic and paucisymptomatic hyponatremic patients. Urea is a non-toxic, cheap product, and protects against osmotic demyelinating syndrome (ODS in experimental studies. Prospective studies showing the benefit to treat mild chronic hyponatremia due to SIADH and comparing water restriction, urea, high ceiling diuretics, and antivasopressin antagonist antagonist should be done.

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

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    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 

  9. 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...

  10. Stress Signal Network between Hypoxia and ER Stress in Chronic Kidney Disease

    Science.gov (United States)

    Maekawa, Hiroshi; Inagi, Reiko

    2017-01-01

    Chronic kidney disease (CKD) is characterized by an irreversible decrease in kidney function and induction of various metabolic dysfunctions. Accumulated findings reveal that chronic hypoxic stress and endoplasmic reticulum (ER) stress are involved in a range of pathogenic conditions, including the progression of CKD. Because of the presence of an arteriovenous oxygen shunt, the kidney is thought to be susceptible to hypoxia. Chronic kidney hypoxia is induced by a number of pathogenic conditions, including renal ischemia, reduced peritubular capillary, and tubulointerstitial fibrosis. The ER is an organelle which helps maintain the quality of proteins through the unfolded protein response (UPR) pathway, and ER dysfunction associated with maladaptive UPR activation is named ER stress. ER stress is reported to be related to some of the effects of pathogenesis in kidney, particularly in the podocyte slit diaphragm and tubulointerstitium. Furthermore, chronic hypoxia mediates ER stress in blood vessel endothelial cells and tubulointerstitium via several mechanisms, including oxidative stress, epigenetic alteration, lipid metabolism, and the AKT pathway. In summary, a growing consensus considers that these stresses interact via complicated stress signal networks, which leads to the exacerbation of CKD (Figure 1). This stress signal network might be a target for interventions aimed at ameliorating CKD.

  11. 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.

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

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    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.

  13. Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

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    Sheela Vyas

    2016-01-01

    Full Text Available Stress and stress hormones, glucocorticoids (GCs, exert widespread actions in central nervous system, ranging from the regulation of gene transcription, cellular signaling, modulation of synaptic structure, and transmission and glial function to behavior. Their actions are mediated by glucocorticoid and mineralocorticoid receptors which are nuclear receptors/transcription factors. While GCs primarily act to maintain homeostasis by inducing physiological and behavioral adaptation, prolonged exposure to stress and elevated GC levels may result in neuro- and psychopathology. There is now ample evidence for cause-effect relationships between prolonged stress, elevated GC levels, and cognitive and mood disorders while the evidence for a link between chronic stress/GC and neurodegenerative disorders such as Alzheimer’s (AD and Parkinson’s (PD diseases is growing. This brief review considers some of the cellular mechanisms through which stress and GC may contribute to the pathogenesis of AD and PD.

  14. Chronic Stress Facilitates the Development of Deep Venous Thrombosis

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    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.

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

    OpenAIRE

    Miranda-Díaz, Alejandra Guillermina; Pazarín-Villaseñor, Leonardo; Yanowsky-Escatell, Francisco Gerardo; 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 disea...

  16. Cerebral perfusion and neuropsychological follow up in mild traumatic brain injury : Acute versus chronic disturbances?

    NARCIS (Netherlands)

    Metting, Zwany; Spikman, Jacoba M.; Rodiger, Lars A.; van der Naalt, Joukje

    2014-01-01

    In a subgroup of patients with mild traumatic brain injury (TBI) residual symptoms, interfering with outcome and return to work, are found. With neuropsychological assessment cognitive deficits can be demonstrated although the pathological underpinnings of these cognitive deficits are not fully unde

  17. Beneficial Effects of Nitric Oxide Induced Mild Oxidative Stress on Post-Thawed Bull Semen Quality

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    Mohsen Sharafi

    2015-07-01

    Full Text Available Background: Cryopreservation of semen requires optimized conditions to minimize the harmful effects of various stresses. The main approach for protection of sperm against stress is based on the use of antioxidants and cryoprotectants, which are described as defensive methods. Recently, the application of controlled mild stressors has been described for activation of a temporary response in oocyte, embryo and somatic cells. In this study a sub-lethal oxidative stress induced by precise concentrations of nitric oxide (NO has been evaluated for sperm during cryopreservation. Materials and Methods: In this experimental study, we used different concentrations of NO [0 μM (NO-0, 0.01 μM (NO-0.01, 0.1 μM (NO-0.1, 1 μM (NO-1, 10 μM (NO-10 and 100 μM (NO-100] during cryopreservation of bull semen. Their effects on post-thawed sperm quality that included motility and velocity parameters, plasma membrane functionality, acrosome integrity, apoptosis status, mitochondrial activity and lipid peroxidation after freezing-thawing were investigated. Results: Exposure of sperm before freezing to NO-1 significantly increased total motility (88.4 ± 2.8%, progressive motility (50.4 ± 3.2% and average path velocity (VAP, 53.8 ± 3.1 μm/s compared to other extenders. In addition, NO-1 significantly increased plasma membrane functionality (89.3 ± 2.9% compared to NO-0 (75.3 ± 2.9%, NO-0.01 (78.3 ± 2.9%, NO-0.1 (76.4 ± 2.9%, NO-10 (64 ± 2.9% and NO-100 (42 ± 2.9%. Sperm exposed to NO-1 produced the highest percentage of viable (85.6 ± 2.3% and the lowest percentage of apoptotic (10.8 ± 2.4% spermatozoa compared to the other extenders. Also, NO-100 resulted in a higher percentage of dead spermatozoa (27.1 ± 2.7% compared to the other extenders. In terms of mitochondrial activity, there was no significant difference among NO-0 (53.4 ± 3.2, NO-0.01 (52.1 ± 3.2, NO-0.1 (50.8 ± 3.2 and NO-1 (53.1 ± 3.2. For acrosome integrity, no significant different

  18. Subchronic and mild social defeat stress alter mouse nest building behavior.

    Science.gov (United States)

    Otabi, Hikari; Goto, Tatsuhiko; Okayama, Tsuyoshi; Kohari, Daisuke; Toyoda, Atsushi

    2016-01-01

    Behavioral and physiological evaluations of animal models of depression are essential to thoroughly understand the mechanisms of depression in humans. Various models have been developed and characterized, and the socially defeated mouse has been widely used for studying depression. Here, we developed and characterized a mouse model of social aversion using a subchronic and mild social defeat stress (sCSDS) paradigm. Compared to control mice, sCSDS mice showed significantly increased body weight gain, water intake, and social aversion to dominant mice on the social interaction test. We observed nest building behavior in sCSDS mice using the pressed cotton as a nest material. Although sCSDS mice eventually successfully built nests, the onset of nest building was severely delayed compared to control mice. The underlying mechanism of this significant delay in nest building by sCSDS mice is unclear. However, our results demonstrate that nest building evaluation is a simple and useful assay for understanding behavior in socially defeated mice and screening drugs such as antidepressants.

  19. Connecting combat-related mild traumatic brain injury with posttraumatic stress disorder symptoms through brain imaging.

    Science.gov (United States)

    Costanzo, Michelle E; Chou, Yi-Yu; Leaman, Suzanne; Pham, Dzung L; Keyser, David; Nathan, Dominic E; Coughlin, Mary; Rapp, Paul; Roy, Michael J

    2014-08-01

    Mild traumatic brain injury (mTBI) and posttraumatic stress disorder (PTSD) may share common symptom and neuropsychological profiles in military service members (SMs) following deployment; while a connection between the two conditions is plausible, the relationship between them has been difficult to discern. The intent of this report is to enhance our understanding of the relationship between findings on structural and functional brain imaging and symptoms of PTSD. Within a cohort of SMs who did not meet criteria for PTSD but were willing to complete a comprehensive assessment within 2 months of their return from combat deployment, we conducted a nested case-control analysis comparing those with combat-related mTBI to age/gender-matched controls with diffusion tensor imaging, resting state functional magnetic resonance imaging and a range of psychological measures. We report degraded white matter integrity in those with a history of combat mTBI, and a positive correlation between the white matter microstructure and default mode network (DMN) connectivity. Higher clinician-administered and self-reported subthreshold PTSD symptoms were reported in those with combat mTBI. Our findings offer a potential mechanism through which mTBI may alter brain function, and in turn, contribute to PTSD symptoms.

  20. Systemic Oxidative Stress and Conversion to Dementia of Elderly Patients with Mild Cognitive Impairment

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    Carlo Cervellati

    2014-01-01

    Full Text Available Mild cognitive impairment (MCI is regarded as a prodromal phase of late onset Alzheimer’s disease (LOAD. It has been proposed that oxidative stress (OxS might be implicated in the pathogenesis of LOAD. The aim of this study was to investigate whether a redox imbalance measured as serum level of hydroperoxides (i.e., by-products of lipid peroxidation and/or serum antioxidant capacity might be predictive of the clinical progression of MCI to LOAD. The levels of these two markers were measured in 111 patients with MCI (follow-up: 2.0 ± 0.6 years, 105 patients with LOAD, and 118 nondemented healthy controls. Multivariate analysis adjusted for potential confounding factors, including age, gender, smoking, and comorbidities, showed a significant increase (P<0.05 in baseline levels of OxS in MCI and LOAD as compared to cognitive healthy controls. No differences in either of OxS markers were found by comparing MCI patients who converted (n = 29 or not converted (n = 82 to LOAD. Overall, these results suggest that systemic OxS might be a precocious feature of MCI and LOAD. However, the role of OxS as an early prognostic marker of progression to LOAD needs further investigations.

  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. [Chronic stress and epigenetics. Relation between academic sciences and theology].

    Science.gov (United States)

    Simon, Kornél

    2012-04-08

    The author gives a short account on the principles of Selye's stress theory, and discusses similarities and dissimilarities of acute and chronic stress. Both the external, and the internal environment, as well as the psycho-mental status are involved in the notion of the environment. Basic principles of epigenetics are reviewed: interaction between environment and genes, neuroendocrine and enzymatic mechanisms involved in silencing and activation of genes, notions of phenotypic plasticity, and epigenetic reprogramming are discussed. Epigenetic mechanisms of interrelation between pathological clinical states (diseases) and the characteristic phenotypes, causative role of psycho-mental status in evoking pathological somatic alterations, and the potential therapeutic consequences are briefly discussed. The etiological role of chronic, civilization stress in producing the worldwide increment of cardiovascular morbidity is cited, argumentation and criticism of the current therapeutical practice is discussed. The author concludes that recent advances in epigenetic knowledge seem to solve the controversy between the academic and theological sciences.

  5. Mild social stress in mice produces opioid-mediated analgesia in visceral but not somatic pain states.

    Science.gov (United States)

    Pitcher, M H; Gonzalez-Cano, R; Vincent, K; Lehmann, M; Cobos, E J; Coderre, T J; Baeyens, J M; Cervero, F

    2017-02-17

    Visceral pain has a greater emotional component than somatic pain. To determine if the stress-induced analgesic response is differentially expressed in visceral versus somatic pain states, we studied the effects of a mild social stressor in either acute visceral or somatic pain states in mice. We show that the presence of an unfamiliar conspecific (stranger) in an adjacent cubicle of a standard transparent observation box produced elevated plasma corticosterone levels compared to mice tested alone, suggesting that the mere presence of a stranger is stressful. We then observed noxious visceral or somatic stimulation-induced nociceptive behavior in mice tested alone or under mildly stressful conditions (i.e. beside an unfamiliar stranger). Compared to mice tested alone, the presence of a stranger produced a dramatic opioid-dependent reduction in pain behavior associated with visceral but not somatic pain. This social stress-induced reduction of visceral pain behavior relied on visual but not auditory/olfactory cues. These findings suggest that visceral pain states may provoke heightened responsiveness to mild stressors, an effect that could interfere with testing outcomes during simultaneous behavioral testing of multiple rodents.

  6. 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.

  7. Dirty electricity, chronic stress, neurotransmitters and disease.

    Science.gov (United States)

    Milham, Samuel; Stetzer, David

    2013-12-01

    Dirty electricity, also called electrical pollution, is high-frequency voltage transients riding along the 50 or 60 Hz electricity provided by the electric utilities. It is generated by arcing, by sparking and by any device that interrupts current flow, especially switching power supplies. It has been associated with cancer, diabetes and attention deficit hyperactivity disorder in humans. Epidemiological evidence also links dirty electricity to most of the diseases of civilization including cancer, cardiovascular disease, diabetes and suicide, beginning at the turn of the twentieth century. The dirty electricity level in a public library was reduced from over 10 000 Graham/Stetzer (G/S) units to below 50 G/S units by installing plug-in capacitive filters. Before cleanup, the urinary dopamine level of only one of seven volunteers was within normal levels, while four of seven phenylethylamine levels were normal. After an initial decline, over the next 18 weeks the dopamine levels gradually increased to an average of over 215 μg/g creatinine, which is well above 170 μg/g creatinine, the high normal level for the lab. Average phenylethylamine levels also rose gradually to slightly above 70 μg/g creatinine, the high normal level for the lab. Neurotransmitters may be biomarkers for dirty electricity and other electromagnetic field exposures. We believe that dirty electricity is a chronic stressor of electrified populations and is responsible for many of their disease patterns.

  8. Oxidative-stress-induced epigenetic changes in chronic diabetic complications.

    Science.gov (United States)

    Feng, Biao; Ruiz, Michael Anthony; Chakrabarti, Subrata

    2013-03-01

    Oxidative stress plays an important role in the development and progression of chronic diabetic complications. Diabetes causes mitochondrial superoxide overproduction in the endothelial cells of both large and small vessels. This increased superoxide production causes the activation of several signal pathways involved in the pathogenesis of chronic complications. In particular, endothelial cells are major targets of glucose-induced oxidative damage in the target organs. Oxidative stress activates cellular signaling pathways and transcription factors in endothelial cells including protein kinase C (PKC), c-Jun-N-terminal kinase (JNK), p38 mitogen-activated protein kinase (MAPK), forkhead box O (FOXO), and nuclear factor kappa-B (NF-κB). Oxidative stress also causes DNA damage and activates DNA nucleotide excision repair enzymes including the excision repair cross complimenting 1(ERCC1), ERCC4, and poly(ADP-ribose) polymerase (PARP). Augmented production of histone acetyltransferase p300, and alterations of histone deacetylases, including class III deacetylases sirtuins, are also involved in this process. Recent research has found that small noncoding RNAs, like microRNA, are a new kind of regulator associated with chronic diabetic complications. There are extensive and complicated interactions and among these molecules. The purpose of this review is to demonstrate the role of oxidative stress in the development of diabetic complications in relation to epigenetic changes such as acetylation and microRNA alterations.

  9. Gene expression profile of rat left ventricles reveals persisting changes following chronic mild exercise protocol: implications for cardioprotection

    Directory of Open Access Journals (Sweden)

    Esposito Fabio

    2009-07-01

    Full Text Available Abstract Background Epidemiological studies showed that physical exercise, specifically moderate lifelong training, is protective against cardiovascular morbidity and mortality. Most experimental work has focused into the effects and molecular mechanisms underlying intense, rather than mild exercise, by exploring the acute effect of training. Our study aims at investigating the cardioprotective effect of mild chronic exercise training and the gene expression profile changes at 48 hrs after the exercise cessation. Rats were trained at mild intensity on a treadmill: 25 m/min, 10%incline, 1 h/day, 3 days/week, 10 weeks; about 60% of the maximum aerobic power. By Affymetrix technology, we investigated the gene expression profile induced by exercise training in the left ventricle (LV of trained (n = 10 and control (n = 10 rats. Cardioprotection was investigated by ischemia/reperfusion experiments (n = 10 trained vs. n = 10 control rats. Results Mild exercise did not induce cardiac hypertrophy and was cardioprotective as demonstrated by the decreased infarct size (p = 0.02 after ischemia/reperfusion experiments in trained with respect to control rats. Ten genes and 2 gene sets (two pathways resulted altered in LV of exercised animals with respect to controls. We validated by real-time PCR the increased expression of four genes: similar to C11orf17 protein (RGD1306959, caveolin 3, enolase 3, and hypoxia inducible factor 1 alpha. Moreover, caveolin 3 protein levels were higher in exercised than control rats by immunohistochemistry and Western Blot analysis. Interestingly, the predicted gene similar to C11orf17 protein (RGD1306959 was significantly increased by exercise. This gene has a high homology with the human C11orf17 (alias: protein kinase-A interacting protein 1 or breast cancer associated gene 3. This is the first evidence that this gene is involved in the response to the exercise training. Conclusion Our data indicated that few, but significant

  10. Respiratory Consequences of Mild-to-Moderate Obesity: Impact on Exercise Performance in Health and in Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Denis E. O'Donnell

    2012-01-01

    Full Text Available In many parts of the world, the prevalence of obesity is increasing at an alarming rate. The association between obesity, multiple comorbidities, and increased mortality is now firmly established in many epidemiological studies. However, the link between obesity and exercise intolerance is less well studied and is the focus of this paper. Although exercise limitation is likely to be multifactorial in obesity, it is widely believed that the respiratory mechanical constraints and the attendant dyspnea are important contributors. In this paper, we examined the evidence that critical ventilatory constraint is a proximate source of exercise limitation in individuals with mild-to-moderate obesity. We first reviewed existing information on exercise performance, including ventilatory and perceptual response patterns, in obese individuals who are otherwise healthy. We then considered the impact of obesity in patients with preexisting respiratory mechanical abnormalities due to chronic obstructive pulmonary disease (COPD, with particular reference to the effect on dyspnea and exercise performance. Our main conclusion, based on the existing and rather sparse literature on the subject, is that abnormalities of dynamic respiratory mechanics are not likely to be the dominant source of dyspnea and exercise intolerance in otherwise healthy individuals or in patients with COPD with mild-to-moderate obesity.

  11. Association between macular degeneration and mild to moderate chronic kidney disease: A nationwide population-based study.

    Science.gov (United States)

    Chen, Chun-Yu; Dai, Ciou-Sia; Lee, Chin-Chan; Shyu, Yu-Chiau; Huang, Ting-Shuo; Yeung, Ling; Sun, Chi-Chin; Yang, Huang-Yu; Wu, I-Wen

    2017-03-01

    Chronic kidney disease (CKD) and macular degeneration (MD) are 2 grave diseases leading to significant disability secondary to renal failure and blindness. The 2 diseases share not only common risk factors but also similar pathogenic mechanisms to renal and retinal injuries. Previous epidemiological studies indicated association between these 2 diseases. However, this concept is challenged by recent investigations. Patients with mild to moderate CKD (n = 30,696) between January 1, 1995 and December 31, 2005 were selected from the Taiwan National Health Insurance Database. Controls (n = 122,784) were matched by age, gender, diabetes mellitus type 2, and hypertension status (1:4 ratios). The risk of MD was compared between the 2 groups. The mean age of patients was 54.9 ± 15.7 years. The proportion of MD was 2.7% in mild to moderate CKD patients and 1.9% in normal controls (P disease, and peripheral vascular disease, model 2; OR: 1.369; 95% CI: 1.264-1.484; P < 0.001) and all these factors (model 3; OR: 1.320, 95% CI: 1.218-1.431, P < 0.001). This association was consistent in the subanalysis, excluding those patients with diabetic retinopathy. Proper diagnosis and timely intervention should be warranted to retard visual loss of these patients.

  12. 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.

  13. Trans-generational effects of mild heat stress on the life history traits of an aphid parasitoid.

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    Ibrahim Ismaeil

    Full Text Available Temperature changes are common in nature and insects are particularly exposed and sensitive to such variations which can be potential stresses, ultimately affecting life history traits and overall fitness. Braconids have been widely used to study the effects of temperature on host-parasitoid interactions and the present work focused on the solitary endoparasitoid Aphidius ervi Haliday (Hymenoptera: Braconidae Aphidiidae, an efficient biological control agent commercially used against aphids such as the potato aphid Macrosiphum euphorbiae Thomas (Sternorrhyncha: Aphididae. Contrary to previous studies using heat shocks at extreme temperatures, we evaluated the effects of mild heat stresses by transferring young parasitoid adults from the constant temperature of 20°C to either a warm (25°C or hot (28°C temperature, for either 1 h or 48 h. Such treatments are consistent with situations commonly experienced by parasitoids when moved from their rearing conditions to greenhouses or field conditions. The effects were evaluated both on the heat stressed A. ervi adults (G0 (immediate effects and on their first generation (G1 progeny (trans-generational effects. G0 wasps' mortality was significantly affected by the temperature in interaction with the duration of the stress. Longevity of G0 wasps surviving the heat stress was negatively affected by the temperature and females lived longer than males. Heat stress applied to A. ervi parents also had consequences on their G1 progeny whose developmental time, rates of mummification and percentage of parasitoid completing total development were negatively affected. Surprisingly, the egg load at emergence of the G1 female progeny was increased when their mothers had been submitted to a mild heat stress of 25°C or 28°C. These results clearly demonstrate trans-generational phenotypic plasticity, showing that adaptation to thermal stresses may be achieved via maternal effects. This study also sheds light on

  14. Clinical Management of a Patient with Chronic Recurrent Vertigo Following a Mild Traumatic Brain Injury

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    Eric G. Johnson

    2009-01-01

    Full Text Available Vertigo, was provoked and right torsional up-beat nystagmus was observed in a 47-year-old patient when she was placed into the right Hallpike-Dix test position using infrared goggle technology. The clinical diagnosis was benign paroxysmal positional vertigo (BPPV, specifically right posterior canalithiasis, resulting from a mild traumatic brain injury (TBI suffered approximately six-months earlier. Previous medical consultations did not include vestibular system examination, and Meclizine was prescribed to suppress her chief complaint of vertigo. Ultimately, the patient was successfully managed by performing two canalith repositioning maneuvers during a single clinical session. The patient reported 100% resolution of symptoms upon reexamination the following day, and the Hallpike-Dix test was negative. Continued symptom resolution was subjectively reported 10 days postintervention via telephone consultation. This case report supports previous publications concerning the presence of BPPV following TBI and the need for inclusion of vestibular system examination during medical consultation.

  15. Chronic Stress Contributes to Cognitive Dysfunction and Hippocampal Metabolic Abnormalities in APP/PS1 Mice

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    Bing Han

    2017-03-01

    Full Text Available Background/Aims: Stress response is determined by the brain, and the brain is a sensitive target for stress. Our previous experiments have confirmed that once the stress response is beyond the tolerable limit of the brain, particularly that of the hippocampus, it will have deleterious effects on hippocampal structure and function; however, the metabolic mechanisms for this are not well understood. Methods: Here, we used morris water maze, elisa and gas chromatography-time of flight/mass spectrometry to observe the changes in cognition, neuropathology and metabolomics in the hippocampus of APP/PS1 mice and wild-type (C57 mice caused by chronic unpredictable mild stress (CUMS, we also further explored the correlation between cognition and metabolomics. Results: We found that 4 weeks of CUMS aggravated cognitive impairment and increased amyloid-β deposition in APP/PS1 mice, but did not affect C57 mice. Under non-stress conditions, compared with C57 mice, there were 8 different metabolites in APP/PS1 mice. However, following CUMS, 3 different metabolites were changed compared with untreated C57 mice. Compared to APP/PS1 mice, there were 7 different metabolites in APP/PS1+CUMS mice. Among these alterations, 3-hydroxybutyric acid, valine, serine, beta-alanine and o-phosphorylethanolamine, which are involved in sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism. Conclusion: The results indicate that APP/PS1 mice are more vulnerable to stress than C57 mice, and the metabolic mechanisms of stress-related cognitive impairment in APP/PS1 mice are related to multiple pathways and networks, including sphingolipid metabolism, synthesis and degradation of ketone bodies, and amino acid metabolism.

  16. Mild moxibustion at Tianshu (ST 25) decreases expression of prokineticin-1 and prokineticin receptor-1 in colon tissue of rats with chronic visceral hyperalgesia

    Institute of Scientific and Technical Information of China (English)

    Luyi Wu; Chunhui Bao; Linbao Ge; Cili Zhou; Huirong Liu; Li Qi; Tao Yi; Huangan Wu; Xiaomei Wang

    2011-01-01

    Prokineticin-1 and prokineticin receptor-1 play important roles in visceral hypersensitivity and in-flammatory pain. Visceral hypersensitivity is closely associated with irritable bowel syndrome. Mild moxibustion can relieve chronic visceral hyperalgesia in rats with irritable bowel syndrome. We hypothesized that prokineticin-1 and prokineticin receptor-1 is the key target in the mechanism. This study established chronic visceral hyperalgesia rat models by colorectal distention. Protein and mRNA expression of prokineticin-1 and prokineticin receptor-1 were determined by immunohisto-chemical method and fluorescence quantitative-PCR, respectively, and were found to be signifi-cantly increased in visceral hyperalgesic rats. Mild moxibustion at Tianshu (ST 25) decreased prokineticin-1 and prokineticin receptor-1 expression in chronic visceral hyperalgesia rats and lessen the chronic visceral hyperalgesia in rats with irritable bowel syndrome at different levels of colorectal distention pressure.

  17. 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.

  18. The effect of acute and chronic stress on growth.

    Science.gov (United States)

    Sävendahl, Lars

    2012-10-23

    Impaired bone growth is observed in many children exposed to stress, but whether the underlying cause is psychological or secondary to a variety of chronic disorders is unclear. The growth plate is specifically targeted by stress through many different mechanisms, including increased serum concentrations of proinflammatory cytokines and cortisol, as well as impaired actions of the growth hormone (GH)-insulin-like growth factor-1 (IGF-1) axis. Both glucocorticoids, such as cortisol, and proinflammatory cytokines adversely affect several aspects of chondrogenesis in the growth plate, and these effects can be ameliorated by raising local IGF-1 concentrations. However, this intervention does not completely normalize growth. In children with stress related to chronic inflammation, the cornerstone of improving stress-impaired growth remains the judicious use of glucocorticoids while ensuring effective control of the disease process. Specific immunomodulatory therapy that targets the actions of tumor necrosis factor-α (TNFα) is at least partially effective at rescuing linear growth in many children with juvenile idiopathic arthritis (JIA). Patients who do not respond to anti-TNF treatment may be candidates for therapeutic agents that target other proinflammatory cytokines and for GH intervention. Although GH treatment rescues linear growth in some patients with JIA, it is unknown whether GH can rescue growth in those patients who do not respond to anticytokine therapy. Further experimental and clinical studies are needed to explore these and other new potential treatment strategies that could improve bone growth in patients who do not respond to conventional therapy.

  19. 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...

  20. The role of corticosteroids and stress in chronic pain conditions.

    Science.gov (United States)

    McEwen, Bruce S; Kalia, Madhu

    2010-10-01

    The relationship between corticosteroids (endogenous and exogenous) and stress is well known, as is the use of steroids as concomitant treatment in pain management during acute inflammation. In the past, steroids have not been considered the first line of treatment in pain management. In this review, we examine new scientific and clinical evidence that demonstrates the direct role that steroids play in the generation and clinical management of chronic pain. We will discuss the new findings demonstrating the fact that steroids and related mediators produce paradoxical effects on pain such as analgesia, hyperalgesia, and even placebo analgesia. In addition, we will examine the physiologic effect of stress, high allostatic load, and idiopathic disease states such as chronic fatigue syndrome, fibromyalgia, irritable bowel syndrome, and burnout. The recently observed positive relationship between glutaminergic activity in the insula and clinical pain will be examined in the context of understanding the central role of steroids in chronic pain. The complex role of the hypothalamic-pituitary-adrenal axis in pain will be discussed as well as other heterogeneous forms of chronic pain that involve many components of the central nervous system. Components of the hypothalamic-pituitary-adrenal axis have paradoxical effects on certain types of pain that are dependent on dose and on site (whether peripheral or central) and mode of application. Recent studies on glia have shown that they prolong a state of neuronal hypersensitization in the dorsal root ganglia by releasing growth factors and other substances that act on the immune system. We will discuss the implication of these new findings directly linking pain to steroids, stress, and key higher brain regions in the context of future therapeutic targets.

  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. Association of Symptoms Following Mild Traumatic Brain Injury With Posttraumatic Stress Disorder vs Postconcussion Syndrome

    DEFF Research Database (Denmark)

    Lagarde, E.; Salmi, L. R.; Holm, L. W.

    2014-01-01

    IMPORTANCE A proportion of patients experience long-lasting symptoms following mild traumatic brain injury (MTBI). The postconcussion syndrome (PCS), included in the DSM-IV, has been proposed to describe this condition. Because these symptoms are subjective and common to other conditions, there i......IMPORTANCE A proportion of patients experience long-lasting symptoms following mild traumatic brain injury (MTBI). The postconcussion syndrome (PCS), included in the DSM-IV, has been proposed to describe this condition. Because these symptoms are subjective and common to other conditions...

  6. 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.

  7. Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study

    OpenAIRE

    Sturm, Gisela; Kollerits, Barbara; Neyer, Ulrich; Ritz, Eberhard; Kronenberg, Florian

    2008-01-01

    Uric acid as a risk factor for progression of non-diabetic chronic kidney disease? The Mild to Moderate Kidney Disease (MMKD) Study correspondence: Corresponding author. Tel.: +43 5129003 70560; fax: +43 5129003 73560or73561. (Kronenberg, Florian) (Kronenberg, Florian) Division of Genetic Epidemiology; Department of Medical Genetics, Molecular and Clinical Pharmacology; Innsbruck Medical University - AUSTRIA (Stur...

  8. 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.

  9. Chronic Mild Hyperglycemia in GCK-MODY Patients Does Not Increase Carotid Intima-Media Thickness

    Directory of Open Access Journals (Sweden)

    Stepanka Pruhova

    2013-01-01

    Full Text Available Aim. GCK-MODY is an autosomal dominant form of diabetes caused by heterozygous mutations in the glucokinase gene leading to a lifelong mild hyperglycemia. The risk of macrovascular complications is considered low, but studies are limited. We, therefore, investigated the carotid intima-media thickness (CIMT as an indicator of macrovascular complications in a group of patients with GCK-MODY. Methods. Twenty-seven GCK mutation carriers and 24 controls recruited among their first-degree relatives were compared, all aging over 35 years. The CIMT was tested using a high-resolution B-mode carotid ultrasonography. Medical history, anthropometry, and biochemical blood workup were obtained. Results. The mean CIMT was 0.707 ± 0.215 mm (mean ± SD in GCK mutation carriers and 0.690 ± 0.180 mm in control individuals. When adjusted for age, gender, and family status, the estimated mean difference in CIMT between the two groups increased to 0.049 mm (P=0.19. No difference was detected for other characteristics, with the exception of fasting blood glucose (GCK-MODY 7.6 mmol/L ± 1.2 (136.4 mg/dL; controls 5.3 mmol/L ± 0.3 (95.4 mg/dL; P<0.0001 and glycated hemoglobin HbA1c (GCK-MODY 6.9% ± 1.0%, 52 mmol/mol ± 10; controls 5.7% ± 0.4%, 39 mmol/mol ± 3; P<0.0001. The frequency of myocardial infarction and ischemic stroke did not differ between groups. Conclusion. Our data indicate that the persistent hyperglycemia in GCK-MODY is associated with a low risk of developing diabetic macrovascular complications.

  10. 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.

  11. Central immune alterations in passive strategy following chronic defeat stress.

    Science.gov (United States)

    Joana, Perez-Tejada; Amaia, Arregi; Arantza, Azpiroz; Garikoitz, Beitia; Eneritz, Gomez-Lazaro; Larraitz, Garmendia

    2016-02-01

    The relationship between stress, mood disorders and immune disorders is known, but what remains to be resolved is why certain individuals are more susceptible than others to suffer different disorders, along with the biological mechanisms that underlie these differences. The objective of this study was to analyze the changes in the expression patterns of proinflammatory cytokines in the hypothalamus, hippocampus, amygdala and prefrontal cortex after chronic defeat, depending on the coping strategy used. The expression levels of α1b and α2a adrenergic receptors and cytokine-inducible nitric oxide synthase (iNOS) in the prefrontal cortex were also measured. The results indicated that subjects with a passive coping strategy showed high levels of interleukin-6 (IL-6) and interleukin-1β (IL-1β) expression in several cerebral structures in resting conditions after 21 days of chronic stress and increases in these cytokine levels in the hippocampus following an additional stress. Low expression levels of tumour necrosis factor-alpha (TNF-α) in the prefrontal cortex in active subjects at rest and in passive subjects after an additional defeat were detected. The iNOS expression levels were lower in the prefrontal cortex of the active group at rest. With respect to adrenergic receptor expression, there were no changes as a function of stress, but there were changes as a function of coping strategy. These results indicate differences in the variables studied in terms of the coping strategy adopted, with passive subjects having a biological profile that could be considered more vulnerable to the development of stress-related disorders.

  12. Stress coping mechanisms in patients with chronic dermatoses

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    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.

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    Science.gov (United States)

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

    2016-05-01

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

  15. Pulmonary oxidative stress is increased in cyclooxygenase-2 knockdown mice with mild pulmonary hypertension induced by monocrotaline.

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    Francesca Seta

    Full Text Available The aim of this study was to examine the role of cyclooxygenase-2 (COX-2 and downstream signaling of prostanoids in the pathogenesis of pulmonary hypertension (PH using mice with genetically manipulated COX-2 expression. COX-2 knockdown (KD mice, characterized by 80-90% suppression of COX-2, and wild-type (WT control mice were treated weekly with monocrotaline (MCT over 10 weeks. Mice were examined for cardiac hypertrophy/function and right ventricular pressure. Lung histopathological analysis was performed and various assays were carried out to examine oxidative stress, as well as gene, protein, cytokine and prostanoid expression. We found that MCT increased right ventricular systolic and pulmonary arterial pressures in comparison to saline-treated mice, with no evidence of cardiac remodeling. Gene expression of endothelin receptor A and thromboxane synthesis, regulators of vasoconstriction, were increased in MCT-treated lungs. Bronchoalveolar lavage fluid and lung sections demonstrated mild inflammation and perivascular edema but activation of inflammatory cells was not predominant under the experimental conditions. Heme oxygenase-1 (HO-1 expression and indicators of oxidative stress in lungs were significantly increased, especially in COX-2 KD MCT-treated mice. Gene expression of NOX-4, but not NOX-2, two NADPH oxidase subunits crucial for superoxide generation, was induced by ∼4-fold in both groups of mice by MCT. Vasodilatory and anti-aggregatory prostacyclin was reduced by ∼85% only in MCT-treated COX-2 KD mice. This study suggests that increased oxidative stress-derived endothelial dysfunction, vasoconstriction and mild inflammation, exacerbated by the lack of COX-2, contribute to the pathogenesis of early stages of PH when mild hemodynamic changes are evident and not yet accompanied by vascular and cardiac remodeling.

  16. Blast Exposure Induces Post-Traumatic Stress Disorder-Related Traits in a Rat Model of Mild Traumatic Brain Injury

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    Elder, Gregory A; Dorr, Nathan P.; De Gasperi, Rita; Gama Sosa, Miguel A.; Shaughness, Michael C.; Maudlin-Jeronimo, Eric; Hall, Aaron A; McCarron, Richard M.; Ahlers, Stephen T

    2012-01-01

    Blast related traumatic brain injury (TBI) has been a major cause of injury in the wars in Iraq and Afghanistan. A striking feature of the mild TBI (mTBI) cases has been the prominent association with post-traumatic stress disorder (PTSD). However, because of the overlapping symptoms, distinction between the two disorders has been difficult. We studied a rat model of mTBI in which adult male rats were exposed to repetitive blast injury while under anesthesia. Blast exposure induced a variety ...

  17. Skin Autofluorescence and Subclinical Atherosclerosis in Mild to Moderate Chronic Kidney Disease: A Case-Control Study

    Science.gov (United States)

    Sánchez, Enric; Betriu, Àngels; Arroyo, David; López, Carolina; Hernández, Marta; Rius, Ferran; Fernández, Elvira

    2017-01-01

    Advanced glycation end-products (AGEs) are increased and predict mortality in patients with chronic kidney disease (CKD) who are undergoing hemodialysis, irrespective of the presence of type 2 diabetes. However, little information exits about the relationship between AGEs and subclinical atherosclerosis at the early stages of CKD. A case-control study was performed including 87 patients with mild-to-moderate stages of CKD (glomerular filtration rate from 89 to 30 ml/min/per 1.73m2) and 87 non-diabetic non-CKD subjects matched by age, gender, body mass index, and waist circumference. Skin autofluorescence (AF), a non-invasive assessment of AGEs, was measured. The presence of atheromatous disease in carotid and femoral arteries was evaluated using vascular ultrasound, and vascular age and SCORE risk were estimated. Patients with mild-to-moderate stages of CKD showed an increase in skin AF compared with control subjects (2.5±0.6 vs. 2.2±0.4 AU, p2.0 AU was accompanied by a 3-fold increased risk of detecting the presence of an atheromathous plaque (OR 3.0, 95% CI 1.4–6.5, p = 0.006). When vascular age was assessed through skin AF, subjects with CKD were almost 12 years older than control subjects (70.3±25.5 vs. 58.5±20.2 years, p = 0.001). Skin AF was negatively correlated with glomerular filtration rate (r = -0.354, p<0.001) and LDL-cholesterol (r = -0.269, p = 0.001), and positively correlated with age (r = 0.472, p<0.001), pulse pressure (r = 0.238, p = 0.002), and SCORE risk (r = 0.451, p<0.001). A stepwise multivariate regression analysis showed that age and glomerular filtration rate independently predicted skin AF (R2 = 0.289, p<0.001). Skin AF is elevated in patients with mild-to-moderate CKD compared with control subjects. This finding may be independently associated with the glomerular filtration rate and the presence of subclinical atheromatous disease. Therefore, the use of skin AF may help to accurately evaluate the real cardiovascular risk at the

  18. 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.

  19. Chronic traumatic encephalopathy in an Iraqi war veteran with posttraumatic stress disorder who committed suicide.

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    Omalu, Bennet; Hammers, Jennifer L; Bailes, Julian; Hamilton, Ronald L; Kamboh, M Ilyas; Webster, Garrett; Fitzsimmons, Robert P

    2011-11-01

    Following his discovery of chronic traumatic encephalopathy (CTE) in football players in 2002, Dr. Bennet Omalu hypothesized that posttraumatic stress disorder (PTSD) in military veterans may belong to the CTE spectrum of diseases. The CTE surveillance at the Brain Injury Research Institute was therefore expanded to include deceased military veterans diagnosed with PTSD. The authors report the case of a 27-year-old United States Marine Corps (USMC) Iraqi war veteran, an amphibious assault vehicle crewman, who committed suicide by hanging after two deployments to Fallujah and Ramadi. He experienced combat and was exposed to mortar blasts and improvised explosive device blasts less than 50 m away. Following his second deployment he developed a progressive history of cognitive impairment, impaired memory, behavioral and mood disorders, and alcohol abuse. Neuropsychiatric assessment revealed a diagnosis of PTSD with hyperarousal (irritability and insomnia) and numbing. He committed suicide approximately 8 months after his honorable discharge from the USMC. His brain at autopsy appeared grossly unremarkable except for congestive brain swelling. There was no atrophy or remote focal traumatic brain injury such as contusional necrosis or hemorrhage. Histochemical and immunohistochemical brain tissue analysis revealed CTE changes comprising multifocal, neocortical, and subcortical neurofibrillary tangles and neuritic threads (ranging from none, to sparse, to frequent) with the skip phenomenon, accentuated in the depths of sulci and in the frontal cortex. The subcortical white matter showed mild rarefaction, sparse perivascular and neuropil infiltration by histiocytes, and mild fibrillary astrogliosis. Apolipoprotein E genotype was 3/4. The authors report this case as a sentinel case of CTE in an Iraqi war veteran diagnosed with PTSD to possibly stimulate new lines of thought and research in the possible pathoetiology and pathogenesis of PTSD in military veterans as part of

  20. Transcranial LED therapy for cognitive dysfunction in chronic, mild traumatic brain injury: two case reports

    Science.gov (United States)

    Naeser, Margaret A.; Saltmarche, Anita; Krengel, Maxine H.; Hamblin, Michael R.; Knight, Jeffrey A.

    2010-02-01

    Two chronic, traumatic brain injury (TBI) cases are presented, where cognitive function improved following treatment with transcranial light emitting diodes (LEDs). At age 59, P1 had closed-head injury from a motor vehicle accident (MVA) without loss of consciousness and normal MRI, but unable to return to work as development specialist in internet marketing, due to cognitive dysfunction. At 7 years post-MVA, she began transcranial LED treatments with cluster heads (2.1" diameter with 61 diodes each - 9x633nm, 52x870nm; 12-15mW per diode; total power, 500mW; 22.2 mW/cm2) on bilateral frontal, temporal, parietal, occipital and midline sagittal areas (13.3 J/cm2 at scalp, estimated 0.4 J/cm2 to brain cortex per area). Prior to transcranial LED, focused time on computer was 20 minutes. After 2 months of weekly, transcranial LED treatments, increased to 3 hours on computer. Performs nightly home treatments (now, 5 years, age 72); if stops treating >2 weeks, regresses. P2 (age 52F) had history of closed-head injuries related to sports/military training and recent fall. MRI shows fronto-parietal cortical atrophy. Pre-LED, was not able to work for 6 months and scored below average on attention, memory and executive function. Performed nightly transcranial LED treatments at home (9 months) with similar LED device, on frontal and parietal areas. After 4 months of LED treatments, returned to work as executive consultant, international technology consulting firm. Neuropsychological testing (post- 9 months of transcranial LED) showed significant improvement in memory and executive functioning (range, +1 to +2 SD improvement). Case 2 reported reduction in PTSD symptoms.

  1. Concussion/mild traumatic brain injury-related chronic pain in males and females: A diagnostic modelling study

    Science.gov (United States)

    Mollayeva, Tatyana; Cassidy, J. David; Shapiro, Colin M.; Mollayeva, Shirin; Colantonio, Angela

    2017-01-01

    Abstract Pain is an unpleasant, complex, and perceived experience that places a significant burden on patients and clinicians. Its severity may be mediated by emotion, attitude, and environmental influences, and pain may be expressed differently in males and females. Traumatic brain injury (TBI) is frequently associated with chronic pain. This diagnostic modeling study examined sex differences in the construct of chronic pain in patients with delayed recovery from concussion/mild traumatic brain injury (mTBI). Data were collected from standardized questionnaires, neuroimaging records, and comprehensive clinical assessments. Bivariate associations were calculated using the Spearman correlation coefficient or analysis of variance. We established sex-specific stepwise multivariate linear regression models of factors associated with pain. Of the 94 participants diagnosed with mTBI (the mean age was 45.20 ± 9.94 years; 61.2% were males; the median time since injury was 197 days [interquartile range 139–416]), head/neck, and bodily pain were reported by 93% and 64%, respectively. No sex differences were identified in pain frequencies or severity. Pain was significantly associated with certain socio-demographic, injury-related, behavioral, and clinical variables. In the multivariable regression analysis, several determinants explained 60% of the pain variance in males and 46% in females. Pain is common in patients with delayed recovery from mTBI and is significantly associated with potentially modifiable clinical and nonclinical variables. Examining the multidimensional construct of pain in concussion/mTBI through a sex lens garners new directions for future longitudinal research on the pain mechanisms involved in postconcussion syndrome. PMID:28207508

  2. High prevalence of chronic pituitary and target-organ hormone abnormalities after blast-related mild traumatic brain injury

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    Charles W. Wilkinson

    2012-02-01

    Full Text Available Studies of traumatic brain injury from all causes have found evidence of chronic hypopituitarism, defined by deficient production of one or more pituitary hormones at least one year after injury, in 25-50% of cases. Most studies found the occurrence of posttraumatic hypopituitarism (PTHP to be unrelated to injury severity. Growth hormone deficiency (GHD and hypogonadism were reported most frequently. Hypopituitarism, and in particular adult GHD, is associated with symptoms that resemble those of PTSD, including fatigue, anxiety, depression, irritability, insomnia, sexual dysfunction, cognitive deficiencies, and decreased quality of life. However, the prevalence of PTHP after blast-related mild TBI (mTBI, an extremely common injury in modern military operations, has not been characterized. We measured concentrations of 12 pituitary and target-organ hormones in two groups of male US Veterans of combat in Iraq or Afghanistan. One group consisted of participants with blast-related mTBI whose last blast exposure was at least one year prior to the study. The other consisted of Veterans with similar military deployment histories but without blast exposure. Eleven of 26, or 42% of participants with blast concussions were found to have abnormal hormone levels in one or more pituitary axes, a prevalence similar to that found in other forms of TBI. Five members of the mTBI group were found with markedly low age-adjusted insulin-like growth factor-I (IGF-I levels indicative of probable GHD, and three had testosterone and gonadotropin concentrations consistent with hypogonadism. If symptoms characteristic of both PTHP and PTSD can be linked to pituitary dysfunction, they may be amenable to treatment with hormone replacement. Routine screening for chronic hypopituitarism after blast concussion shows promise for appropriately directing diagnostic and therapeutic decisions that otherwise may remain unconsidered and for markedly facilitating recovery and

  3. Is it stress? The role of stress related systems in chronic food restriction-induced augmentation of heroin seeking in the rat

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    Firas eSedki

    2013-06-01

    Full Text Available Drug addiction is a chronic disease characterized by recurring episodes of abstinence and relapse. The precise mechanisms underlying this pattern are yet to be elucidated, but stress is thought to be a major factor in relapse. Recently, we reported that rats under withdrawal and exposed to a mild chronic stressor, prolonged food restriction, show increased heroin seeking compared to sated controls. Previous studies demonstrated a critical role for corticotropin-releasing factor (CRF and corticosterone, hormones involved in the stress response, in acute food deprivation-induced reinstatement of extinguished drug seeking. However, the role of CRF and corticosterone in chronic food restriction-induced augmentation of drug seeking remains unknown. Here, male Long-Evans rats were trained to self-administer heroin for 10 days in operant conditioning chambers. Rats were then removed from the training chambers, and subjected to 14 days of unrestricted (sated rats or a mildly restricted (FDR rats access to food, which maintained their body weight at 90% of their baseline weight. On day 14, different groups of rats were administered a selective CRF1 receptor antagonist (R121919; 0.0, 20.0 mg/kg; s.c., a non-selective CRF receptor antagonist (α-helical CRF; 0.0, 10.0, 25.0 μg/μl; i.c.v. or a glucocorticoid receptor antagonist (RU486; 0.0, 30.0 mg/kg; i.p., and underwent a 1 h drug seeking test under extinction conditions. An additional group of rats was tested following adrenalectomy. All FDR rats showed a statistically significant increase in heroin seeking compared to the sated rats. No statistically significant effects for treatment with α-helical CRF, R121919, RU486 or adrenalectomy were observed. These findings suggest that stress may not be a critical factor in the augmentation of heroin seeking in food-restricted rats.

  4. Potential antiinflammatory effects of acupuncture in a chronic stress model of depression in rats.

    Science.gov (United States)

    Lu, Jun; Shao, Run-Hui; Hu, Li; Tu, Ya; Guo, Jian-You

    2016-04-08

    Accumulating evidence indicates that inflammation may contribute to the pathophysiology of depression. Acupuncture in traditional Chinese medicine has been considered an effective treatment for depression. However, whether the mechanisms that underlie the antidepressant effect of acupuncture are related to its antiinflammatory properties remains unclear. In the present study, rats were exposed to chronic unpredictable mild stress (CUMS) for 28 days to induce depressive-like behavior. Body weight, sucrose preference, and locomotor activity in the open field were measured. After the behavioral tests, reverse transcription polymerase chain reaction was used to determine the mRNA expression of proinflammatory cytokines (interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]), and enzyme-linked immunosorbent assay was used to detect cytokine concentrations. CUMS rats exhibited decrease in body weight, sucrose preference, and locomotor activity in the open field test. Chronic acupuncture and fluoxetine treatment reversed CUMS-induced depressive-like behavior. Compared with control rats, the mRNA and protein expression of IL-1β, IL-6, and TNF-α in the hippocampus and prefrontal cortex and cytokine concentrations in serum significantly increased in CUMS rats. Acupuncture and fluoxetine treatment significantly decreased the levels of proinflammatory cytokines in the hippocampus, prefrontal cortex, and serum. These results suggest that acupuncture has antidepressant-like effects, and its mechanism of action appears to involve the inhibition of proinflammatory cytokines.

  5. Mangifera indica Fruit Extract Improves Memory Impairment, Cholinergic Dysfunction, and Oxidative Stress Damage in Animal Model of Mild Cognitive Impairment

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    Jintanaporn Wattanathorn

    2014-01-01

    Full Text Available To date, the effective preventive paradigm against mild cognitive impairment (MCI is required. Therefore, we aimed to determine whether Mangifera indica fruit extract, a substance possessing antioxidant and cognitive enhancing effects, could improve memory impairment, cholinergic dysfunction, and oxidative stress damage in animal model of mild cognitive impairment. Male Wistar rats, weighing 180–200 g, were orally given the extract at doses of 12.5, 50, and 200 mg·kg−1 BW for 2 weeks before and 1 week after the bilateral injection of AF64A (icv. At the end of study, spatial memory, cholinergic neurons density, MDA level, and the activities of SOD, CAT, and GSH-Px enzymes in hippocampus were determined. The results showed that all doses of extract could improve memory together with the decreased MDA level and the increased SOD and GSH-Px enzymes activities. The increased cholinergic neurons density in CA1 and CA3 of hippocampus was also observed in rats treated with the extract at doses of 50 and 200 mg·kg−1 BW. Therefore, our results suggested that M. indica, the potential protective agent against MCI, increased cholinergic function and the decreased oxidative stress which in turn enhanced memory. However, further researches are essential to elucidate the possible active ingredients and detail mechanism.

  6. 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.

  7. 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.

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

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    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.

  9. 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.

  10. Mild traumatic brain injury with social defeat stress alters anxiety, contextual fear extinction, and limbic monoamines in adult rats

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    Daniel eDavies

    2016-04-01

    Full Text Available Mild traumatic brain injury (mTBI produces symptoms similar to those typifying posttraumatic stress disorder (PTSD in humans. We sought to determine whether a rodent model of stress concurrent with mTBI produces characteristics of PTSD such as impaired contextual fear extinction, while also examining concurrent alterations to limbic monoamine activity in brain regions relevant to fear and anxiety states. Male rats were exposed to social stress or control conditions immediately prior to mTBI induction, and 6 days later were tested either for anxiety-like behavior using the elevated plus maze (EPM, or for contextual fear conditioning and extinction. Brains were collected 24 hr after EPM testing, and tissue from various limbic regions analyzed for content of monoamines, their precursors and metabolites using HPLC with electrochemical detection. Either social defeat or mTBI alone decreased time spent in open arms of the EPM, indicating greater anxiety-like behavior. However, this effect was enhanced by the combination of treatments. Further, rats exposed to both social defeat and mTBI exhibited greater freezing within extinction sessions compared to all other groups, suggesting impaired contextual fear extinction. Social defeat combined with mTBI also had greater effects on limbic monoamines than either insult alone, particularly with respect to serotonergic effects associated with anxiety and fear learning. The results suggest social stress concurrent with mTBI produces provides a relevant animal model for studying the prevention and treatment of post-concussive psychobiological outcomes.

  11. 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.

  12. Problem solving moderates the effects of life event stress and chronic stress on suicidal behaviors in adolescence.

    Science.gov (United States)

    Grover, Kelly E; Green, Kelly L; Pettit, Jeremy W; Monteith, Lindsey L; Garza, Monica J; Venta, Amanda

    2009-12-01

    The present study examined the unique and interactive effects of stress and problem-solving skills on suicidal behaviors among 102 inpatient adolescents. As expected, life event stress and chronic stress each significantly predicted suicidal ideation and suicide attempt. Problem solving significantly predicted suicidal ideation, but not suicide attempt. Problem solving moderated the associations between life event stress and suicidal behaviors, as well as between chronic stress and suicidal ideation, but not chronic stress and suicide attempt. At high levels of stress, adolescents with poor problem-solving skills experienced elevated suicidal ideation and were at greater risk of making a nonfatal suicide attempt. The interactive effects decreased to non-significance after controlling for depressive symptoms and hopelessness. Clinical implications are discussed.

  13. 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.

  14. Comparing chronic interpersonal and noninterpersonal stress domains as predictors of depression recurrence in emerging adults.

    Science.gov (United States)

    Sheets, Erin S; Craighead, W Edward

    2014-12-01

    Understanding how persistent interpersonal difficulties distinctly affect the course of major depressive disorder (MDD) during emerging adulthood is critical, given that early experiences impact future coping resources and functioning. Research on stress and MDD has mostly concentrated on stressful life events, while chronic stress largely has not been explored. The present study examined interpersonal (intimate relationship, close friendships, social life, family relationships) and noninterpersonal (academic, work, financial, personal health, and family members' health) domains of chronic stress as time-varying predictors of depressive recurrence in emerging adults. Baseline assessments identified previously depressed emerging adults (N = 119), who subsequently completed 6-month, 12-month and 18-month follow-up interviews to determine chronic stress experiences and onset of new major depressive episodes. Survival analyses indicated that time-varying total chronic stress and chronic interpersonal stress predicted higher risk for depression recurrence; however, chronic noninterpersonal stress was not associated with recurrence. Intimate relationship stress, close friendship stress, family relationship stress, personal health, and family members' health independently predicted MDD recurrence, over and above well-established depression risk factors of dysfunctional cognitions and personality disorder symptoms. Evidence that interpersonal stress could have substantial impact on course of depression is consistent with theories of emerging adulthood, a time when young people are individuating from the family and experiencing significant social transition.

  15. Increased risk taking in relation to chronic stress in young adults

    Directory of Open Access Journals (Sweden)

    Smarandita eCeccato

    2016-01-01

    Full Text Available 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 learning-independent 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 chronic cortisol exposure. We discovered a significant, positive 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.

  16. Characterizing effects of mild traumatic brain injury and posttraumatic stress disorder on balance impairments in blast-exposed servicemembers and Veterans using computerized posturography.

    Science.gov (United States)

    Wares, Joanna R; Hoke, Kathy W; Walker, William; Franke, Laura Manning; Cifu, David X; Carne, William; Ford-Smith, Cheryl

    2015-01-01

    The high rate of blast exposures experienced by U.S. servicemembers (SMs) during the recent conflicts in Iraq and Afghanistan has resulted in frequent combat-related mild traumatic brain injuries (mTBIs). Dizziness and postural instability can persist after mTBI as a component of postconcussion syndrome, but also occur among the somatic complaints of posttraumatic stress disorder (PTSD). The goals of this study were to examine the use of computerized posturography (CPT) to objectively characterize chronic balance deficits after mTBI and to explore the utility of CPT in distinguishing between combat and blast-exposed participants with and without mTBI and PTSD. Data were analyzed from a subject pool of 166 combat-exposed SMs and Veterans who had a blast experience within the past 2 yr while deployed. Using nonparametric tests and measures of impairment, we found that balance was deficient in participants diagnosed with mTBI with posttraumatic amnesia (PTA) or PTSD versus those with neither and that deficits were amplified for participants with both diagnoses. In addition, unique deficiencies were found using CPT for individuals having isolated mTBI with PTA and isolated PTSD. Computerized balance assessment offers an objective technique to examine the physiologic effects and provide differentiation between participants with combat-associated mTBI and PTSD.

  17. 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.

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

    Science.gov (United States)

    Negrón-Oyarzo, Ignacio; Aboitiz, Francisco; Fuentealba, Pablo

    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 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. PMID:26904302

  19. Acute and chronic effects of erythromycin exposure on oxidative stress and genotoxicity parameters of Oncorhynchus mykiss

    Energy Technology Data Exchange (ETDEWEB)

    Rodrigues, S., E-mail: up201208875@fc.up.pt [Departamento de Biologia da Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169–007 Porto (Portugal); Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Antunes, S.C. [Departamento de Biologia da Faculdade de Ciências da Universidade do Porto (FCUP), Rua do Campo Alegre s/n, 4169–007 Porto (Portugal); Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Correia, A.T. [Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR/CIMAR), Rua dos Bragas 289, 4050–123 Porto (Portugal); Faculdade de Ciências da Saúde da Universidade Fernando Pessoa (FCS-UFP), Rua Carlos da Maia, 296, 4200–150, Porto (Portugal); Nunes, B. [Centro de Estudos do Ambiente e do Mar (CESAM), Campus de Santiago, Universidade de Aveiro, 3810–193 Aveiro (Portugal); Departamento de Biologia, Universidade de Aveiro, Campus de Santiago, 3810–193 Aveiro (Portugal)

    2016-03-01

    Erythromycin (ERY) is a macrolide antibiotic used in human and veterinary medicine, and has been detected in various aquatic compartments. Recent studies have indicated that this compound can exert biological activity on non-target organisms environmentally exposed. The present study aimed to assess the toxic effects of ERY in Oncorhynchus mykiss after acute and chronic exposures. The here adopted strategy involved exposure to three levels of ERY, the first being similar to concentrations reported to occur in the wild, thus ecologically relevant. Catalase (CAT), total glutathione peroxidase (GPx), glutathione reductase (GRed) activities and lipid peroxidation (TBARS levels) were quantified as oxidative stress biomarkers in gills and liver. Genotoxic endpoints, reflecting different types of genetic damage in blood cells, were also determined, by performing analysis of genetic damage (determination of the genetic damage index, GDI, measured by comet assay) and of erythrocytic nuclear abnormalities (ENAs). The results suggest the occurrence of a mild, but significant, oxidative stress scenario in gills. For acutely exposed organisms, significant alterations were observed in CAT and GRed activities, and also in TBARS levels, which however are modifications with uncertain biological interpretation, despite indicating involvement of an oxidative effect and response. After chronic exposure, a significant decrease of CAT activity, increase of GPx activity and TBARS levels in gills was noticed. In liver, significant decrease in TBARS levels were observed in both exposures. Comet and ENAs assays indicated significant increases on genotoxic damage of O. mykiss, after erythromycin exposures. This set of data (acute and chronic) suggests that erythromycin has the potential to induce DNA strand breaks in blood cells, and demonstrate the induction of chromosome breakage and/or segregational abnormalities. Overall results indicate that both DNA damaging effects induced by

  20. Thermotolerance induced at a mild temperature of 40°C alleviates heat shock-induced ER stress and apoptosis in HeLa cells.

    Science.gov (United States)

    Bettaieb, Ahmed; Averill-Bates, Diana A

    2015-01-01

    Hyperthermia (39-45°C) has emerged as an alternate prospect for cancer therapy in combination with radiation and chemotherapy. Despite promising progress in the clinic, molecular mechanisms involved in hyperthermia-induced cell death are not clear. Hyperthermia causes protein denaturation/aggregation, which results in cell death by apoptosis and/or necrosis. Hyperthermia also induces thermotolerance, which renders cells resistant to subsequent exposure to lethal heat shock. This study investigates the role of both lethal (42-43°C) and mild (40°C) hyperthermia in regulating ER stress and ER stress-induced apoptosis in HeLa cells. The ability of mild thermotolerance induced at 40°C to alleviate either or both of these processes is also determined. Hyperthermia (42-43°C) induced ER stress, revealed by phosphorylation of PERK, eIF2α and IRE1α, cleavage of ATF6 and increased expression of BiP and sXBP1. Real-time PCR revealed that mRNA levels of ATF6, ATF4, BiP, sXBP1 and CHOP increased in cells exposed to hyperthermia. Moreover, hyperthermia caused disruption of calcium homeostasis and activated the calpain-calpastatin proteolytic system and ER resident caspase 4. Pre-exposure to mild hyperthermia (40°C) alleviated the induction of cytotoxicity and ER stress by hyperthermia (42-43°C) and protected cells against ER stress-induced apoptosis. ShRNA-mediated depletion of Hsp72 abrogated protective effects of mild thermotolerance (40°C) against heat-shock induced ER stress and sensitized cells to ER stress-mediated apoptosis. Our findings show that Hsp72 contributes to the protective effects of mild hyperthermia (40°C) against hyperthermia-induced ER stress and apoptosis.

  1. Pressure overload-induced mild cardiac hypertrophy reduces leftventricular transmural differences in mitochondrial respiratory chainactivity and increases oxidative stress

    Directory of Open Access Journals (Sweden)

    Michel eKINDO

    2012-08-01

    Full Text Available Objective: Increased mechanical stress and contractility characterizes normal left ventricular subendocardium (Endo but whether Endo mitochondrial respiratory chain complex activities is reduced as compared to subepicardium (Epi and whether pressure overload-induced left ventricular hypertrophy (LVH might modulate transmural gradients through increased reactive oxygen species (ROS production is unknown. Methods: LVH was induced by 6 weeks abdominal aortic banding and cardiac structure and function were determined with echocardiography and catheterization in sham-operated and LVH rats (n=10 for each group. Mitochondrial respiration rates, coupling, content and ROS production were measured in LV Endo and Epi, using saponin-permeabilised fibres, Amplex Red fluorescence and citrate synthase activity.Results: In sham, a transmural respiratory gradient was observed with decreases in endo maximal oxidative capacity (-36.7%, P<0.01 and complex IV activity (-57.4%, P<0.05. Mitochondrial hydrogen peroxide (H2O2 production was similar in both LV layers.Aortic banding induced mild LVH (+31.7% LV mass, associated with normal LV fractional shortening and end diastolic pressure. LVH reduced maximal oxidative capacity (-23.6 and -33.3%, increased mitochondrial H2O2 production (+86.9 and +73.1%, free radical leak (+27.2% and +36.3% and citrate synthase activity (+27.2% and +36.3% in Endo and Epi, respectively.Transmural mitochondrial respiratory chain complex IV activity was reduced in LVH (-57.4 vs –12.2%; P=0.02. Conclusions: Endo mitochondrial respiratory chain complexes activities are reduced compared to LV Epi. Mild LVH impairs mitochondrial oxidative capacity, increases oxidative stress and reduces transmural complex IV activity. Further studies will be helpful to determine whether reduced LV transmural gradient in mitochondrial respiration might be a new marker of a transition from uncomplicated toward complicated LVH.

  2. Simultaneous Treatment of Neurocognitive and Psychiatric Symptoms in Veterans with Post-Traumatic Stress Disorder and History of Mild Traumatic Brain Injury: A Pilot Study of Mindfulness-Based Stress Reduction.

    Science.gov (United States)

    Cole, Michael A; Muir, James J; Gans, Jennifer J; Shin, Lisa M; D'Esposito, Mark; Harel, Brian T; Schembri, Adrian

    2015-09-01

    Treating patient populations with significant psychiatric and neurocognitive symptomatology can present a unique clinical dilemma: progress in psychotherapy can be significantly fettered by cognitive deficits, whereas neurocognitive rehabilitation efforts can be ineffective because of psychiatric overlay. Application of mindfulness-based interventions to address either cognitive or psychiatric symptoms in isolation appears efficacious in many contexts; however, it remains unclear whether this type of intervention might help address simultaneous neurocognitive and psychiatric symptomatology. In a pre-post mixed methods design pilot study, nine Veterans with post-traumatic stress disorder (PTSD) and a history of mild traumatic brain injury with chronic cognitive complaints participated in Mindfulness-Based Stress Reduction (MBSR). Clinical interview, questionnaires, and attention and PTSD measures were administered immediately before, immediately after, and 3 months after MBSR completion. Qualitative and quantitative findings suggest high levels of safety, feasibility, and acceptability. Measurement of attention revealed significant improvement immediately following MBSR (p MBSR (p MBSR (p MBSR completion (p < 0.05, d = -0.93). These results warrant a randomized controlled trial follow-up. Potential mechanisms for the broad effects observed will be explored.

  3. Agomelatine reverses the decrease in hippocampal cell survival induced by chronic mild stress

    NARCIS (Netherlands)

    Dagyte, Girstaute; Crescente, Ilaria; Postema, Folkert; Seguin, Laure; Gabriel, Cecilia; Mocaer, Elisabeth; Den Boer, Johan A.; Koolhaas, Jaap M.; Dagytė, Girstautė

    2011-01-01

    The antidepressant agomelatine is a MT1/MT2 receptor agonist and 5-HT2C antagonist. Its antidepressant activity is proposed to result from the synergy between these sets of receptors. Agomelatine-induced changes in the brain have been reported under basal conditions. Yet, little is known about its e

  4. Adolescent vulnerability to cardiovascular consequences of chronic emotional stress: Review and perspectives for future research.

    Science.gov (United States)

    Crestani, Carlos C

    2017-03-01

    Emotional stress has been recognized as a modifiable risk factor for cardiovascular diseases. Adolescence has been proposed as a developmental period of vulnerability to stress. This idea has been mainly supported by experimental research in animals demonstrating a higher impact of chronic emotional stress in adolescents compared with adults. Adolescent vulnerability is also based on evidence that stress during this developmental period affects development, so that enduring changes are found in adult animals that experienced stress during adolescence. The purpose of the present review is to discuss experimental research in rodent models that investigated the impact of long-term exposure to stressful events during adolescence on cardiovascular function. The development of cardiovascular function and autonomic activity in rodents is initially reviewed. Then, a discussion of an adolescent vulnerability to cardiovascular effects of chronic stress is presented. From the reviewed literature, perspective for future research is proposed to better elucidate adolescent vulnerability to cardiovascular complications evoked by chronic emotional stress.

  5. Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury.

    Science.gov (United States)

    Servatius, Richard J; Marx, Christine E; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D; Naylor, Jennifer C; Pang, Kevin C H

    2016-01-01

    Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  6. Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

    Directory of Open Access Journals (Sweden)

    Richard J Servatius

    2016-08-01

    Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

  7. No Influence of Type 2 Diabetes on Chronic Inflammation and Oxidative Stress in Obese Patients

    Directory of Open Access Journals (Sweden)

    Adriana Florinela CĂTOI

    2014-03-01

    Full Text Available Obesity per se carries the features of chronic inflammation and oxidative stress that interrelate in a complex network and exert an important role in the onset of several complications such as type 2 diabetes, atherosclerosis and cardiovascular events. On the other hand, it seems that hyperglycemia per se as well as insulin resistance (independent of hyperglycemia, both induce increased oxidative stress. The aim of our study was to analyze proinflammatory and oxidative stress markers in obese patients with and without type 2 diabetes and to verify the hypothesis that type 2 diabetes associated with obesity would promote a higher chronic inflammation and oxidative stress state as compared to obesity alone. We found no differences between the two groups of patients regarding chronic inflammation and oxidative stress markers. Therefore we may conclude that there is no influence of type 2 diabetes on chronic inflammation and oxidative stress in obese patients.

  8. Molecular mechanisms of anti-aging hormetic effects of mild heat stress on human cells

    DEFF Research Database (Denmark)

    Rattan, Suresh I S; Eskildsen-Helmond, Yvonne E G; Beedholm, Rasmus

    2004-01-01

    at the levels of maintenance of stress protein profile; reduction in the accumulation of oxidatively and glycoxidatively damaged proteins; stimulation of the proteasomal activities for the degradation of abnormal proteins; improved cellular resistance to ethanol, hydrogenperoxide, and ultraviolet-B rays......; and enhanced levels of various antioxidant enzymes. We are now undertaking a detailed analysis of the signal transduction pathways to determine alterations in the phosphorylation and dephosphorylation states of extracellular signal-related kinase, c-Jun terminal kinase and p38 MAP-kinases as a measure...

  9. Improving patient access and choice: Assisted Bibliotherapy for mild to moderate stress/anxiety in primary care.

    Science.gov (United States)

    Reeves, T; Stace, J M

    2005-06-01

    Current traditional methods of mental healthcare service delivery, based on 'specialists' providing 'outpatient appointments' for formal therapy, are often inappropriate for the needs of patients in primary care. The estimated numbers of adults with mental health problems are immense, and it is this, combined with Department of Health initiatives aimed at improving choice and access, which make it essential that new ways of delivering services are explored. This trial examines the use of an assisted self-help treatment package for mild to moderate stress/anxiety [Assisted Bibliotherapy (AB)] with an adult clinical population referred by their general practitioner. Assisted Bibliotherapy is a brief intervention (8 weeks), with limited therapist contact (20-min sessions). Non-parametric statistical testing of scores from the Zung Anxiety Scale and the Clinical Outcomes in Routine Evaluation (CORE) questionnaire indicated positive results. There was significant improvement at post-treatment, which was maintained at 3 month follow-up. The results from this trial and a previous trial of AB by Kupshik & Fisher in 1999, indicate that it is an effective treatment which could be used as part of a stepped care approach to managing and treating stress/anxiety in primary care.

  10. 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.

  11. 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

  12. 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.

  13. Effects of stress on heart rate complexity--a comparison between short-term and chronic stress.

    Science.gov (United States)

    Schubert, C; Lambertz, M; Nelesen, R A; Bardwell, W; Choi, J-B; Dimsdale, J E

    2009-03-01

    This study examined chronic and short-term stress effects on heart rate variability (HRV), comparing time, frequency and phase domain (complexity) measures in 50 healthy adults. The hassles frequency subscale of the combined hassles and uplifts scale (CHUS) was used to measure chronic stress. Short-term stressor reactivity was assessed with a speech task. HRV measures were determined via surface electrocardiogram (ECG). Because respiration rate decreased during the speech task (p<.001), this study assessed the influence of respiration rate changes on the effects of interest. A series of repeated-measures analyses of covariance (ANCOVA) with Bonferroni adjustment revealed that short-term stress decreased HR D2 (calculated via the pointwise correlation dimension PD2) (p<.001), but increased HR mean (p<.001), standard deviation of R-R (SDRR) intervals (p<.001), low (LF) (p<.001) and high frequency band power (HF) (p=.009). Respiratory sinus arrhythmia (RSA) and LF/HF ratio did not change under short-term stress. Partial correlation adjusting for respiration rate showed that HR D2 was associated with chronic stress (r=-.35, p=.019). Differential effects of chronic and short-term stress were observed on several HRV measures. HR D2 decreased under both stress conditions reflecting lowered functionality of the cardiac pacemaker. The results confirm the importance of complexity metrics in modern stress research on HRV.

  14. 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 (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 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.

  15. Is the Thoroughbred race-horse under chronic stress?

    Directory of Open Access Journals (Sweden)

    G.P. Nogueira

    1997-10-01

    Full Text Available Thoroughbred fillies were divided into three groups according to age: group 1, 7 fillies aged 1 to 2 years (G1 starting the training program; group 2, 9 fillies aged 2 to 3 years (G2 in a full training program; group 3, 8 older fillies 3 to 4 years of age (G3 training and racing. Blood samples were collected weekly from July to December. Cortisol was quantified using a solid phase DPC kit. The intra- and interassay coefficients of variation were 12.5% and 15.65% and sensitivity was 1.9 ± 0.2 nmol/l. The semester average of cortisol levels varied between groups: G1 = 148.8 ± 6.7, G2 = 125.7 ± 5.8, G3 = 101.1 ± 5.4 nmol/l, with G3 differing statistically from the other groups. The lower cortisol levels observed in the older fillies lead us to propose that the stress stimulus, when maintained over a long period of time, may become chronic and result in a reduction of hypophyseal corticotropin-releasing hormone receptors. The secretion of endogenous opioids may also lead to low serum cortisol levels.

  16. Mild systemic oxidative stress in the subclinical stage of Alzheimer's disease.

    Science.gov (United States)

    Giavarotti, Leandro; Simon, Karin A; Azzalis, Ligia A; Fonseca, Fernando L A; Lima, Alessandra F; Freitas, Maria C V; Brunialti, Milena K C; Salomão, Reinaldo; Moscardi, Alcione A V S; Montaño, Maria B M M; Ramos, Luiz R; Junqueira, Virgínia B C

    2013-01-01

    Alzheimer's disease (AD) is a late-onset, progressive degenerative disorder that affects mainly the judgment, emotional stability, and memory domains. AD is the outcome of a complex interaction among several factors which are not fully understood yet; nevertheless, it is clear that oxidative stress and inflammatory pathways are among these factors. 65 elderly subjects (42 cognitively intact and 23 with probable Alzheimer's disease) were selected for this study. We evaluated erythrocyte activities of superoxide dismutase, catalase, and glutathione peroxidase as well as plasma levels of total glutathione, α-tocopherol, β-carotene, lycopene, and coenzyme Q10. These antioxidant parameters were confronted with plasmatic levels of protein and lipid oxidation products. Additionally, we measured basal expression of monocyte HLA-DR and CD-11b, as well as monocyte production of cytokines IL1-α, IL-6, and TNF-α. AD patients presented lower plasmatic levels of α-tocopherol when compared to control ones and also higher basal monocyte HLA-DR expression associated with higher IL-1α production when stimulated by LPS. These findings support the inflammatory theory of AD and point out that this disease is associated with a higher basal activation of circulating monocytes that may be a result of α-tocopherol stock depletion.

  17. Cut-off points for mild, moderate, and severe pain on the visual analogue scale for pain in patients with chronic musculoskeletal pain.

    Science.gov (United States)

    Boonstra, Anne M; Schiphorst Preuper, Henrica R; Balk, Gerlof A; Stewart, Roy E

    2014-12-01

    The aim of this study was to find the cut-off points on the visual analogue scale (VAS) to distinguish among mild, moderate, and severe pain, in relation to the following: pain-related interference with functioning; verbal description of the VAS scores; and latent class analysis for patients with chronic musculoskeletal pain. A total of 456 patients were included. Pain was assessed using the VAS and verbal rating scale; functioning was assessed using the domains of the Short Form (36) Health Survey (SF-36). Eight cut-off point schemes were tested using multivariate analysis of variance (MANOVA), ordinal logistic regression, and latent class analysis. The study results showed that VAS scores ⩽ 3.4 corresponded to mild interference with functioning, whereas 3.5 to 6.4 implied moderate interference, and ⩾ 6.5 implied severe interference. VAS scores ⩽ 3.4 were best described for patients with chronic musculoskeletal pain as mild pain, 3.5 to 7.4 as moderate pain, and ⩾ 7.5 as severe pain. Latent class analysis found that a 3-class solution fitted best, resulting in the classes 0.1 to 3.8, 3.9 to 5.7, and 5.8 to 10 cm. Findings from our study agree with those of some other studies, although many other studies found different optimal cut-off point schemes. As there appear to be no universally accepted cut-off points, and in view of the low-to-moderate associations between VAS scores and functioning and between VAS and verbal rating scale scores, the correct classification of VAS scores as mild, moderate. or severe in clinical practice seems doubtful.

  18. Chronic stress impairs prefrontal cortex-dependent response inhibition and spatial working memory.

    Science.gov (United States)

    Mika, Agnieszka; Mazur, Gabriel J; Hoffman, Ann N; Talboom, Joshua S; Bimonte-Nelson, Heather A; Sanabria, Federico; Conrad, Cheryl D

    2012-10-01

    Chronic stress leads to neurochemical and structural alterations in the prefrontal cortex (PFC) that correspond to deficits in PFC-mediated behaviors. The present study examined the effects of chronic restraint stress on response inhibition (using a response-withholding task, the fixed-minimum interval schedule of reinforcement, or FMI), and working memory (using a radial arm water maze, RAWM). Adult male Sprague-Dawley rats were first trained on the RAWM and subsequently trained on FMI. After acquisition of FMI, rats were assigned to a restraint stress (6h/d/28d in wire mesh restrainers) or control condition. Immediately after chronic stress, rats were tested on FMI and subsequently on RAWM. FMI results suggest that chronic stress reduces response inhibition capacity and motivation to initiate the task on selective conditions when sucrose reward was not obtained on the preceding trial. RAWM results suggest that chronic stress produces transient deficits in working memory without altering previously consolidated reference memory. Behavioral measures from FMI failed to correlate with metrics from RAWM except for one in which changes in FMI timing imprecision negatively correlated with changes in RAWM working memory errors for the controls, a finding that was not observed following chronic stress. Fisher's r-to-z transformation revealed no significant differences between control and stress groups with correlation coefficients. These findings are the first to show that chronic stress impairs both response inhibition and working memory, two behaviors that have never been directly compared within the same animals after chronic stress, using FMI, an appetitive task, and RAWM, a nonappetitive task.

  19. 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.

  20. The negative effect of starvation and the positive effect of mild thermal stress on thermal tolerance of the red flour beetle, Tribolium castaneum.

    Science.gov (United States)

    Scharf, Inon; Wexler, Yonatan; MacMillan, Heath Andrew; Presman, Shira; Simson, Eddie; Rosenstein, Shai

    2016-04-01

    The thermal tolerance of a terrestrial insect species can vary as a result of differences in population origin, developmental stage, age, and sex, as well as via phenotypic plasticity induced in response to changes in the abiotic environment. Here, we studied the effects of both starvation and mild cold and heat shocks on the thermal tolerance of the red flour beetle, Tribolium castaneum. Starvation led to impaired cold tolerance, measured as chill coma recovery time, and this effect, which was stronger in males than females, persisted for longer than 2 days but less than 7 days. Heat tolerance, measured as heat knockdown time, was not affected by starvation. Our results highlight the difficulty faced by insects when encountering multiple stressors simultaneously and indicate physiological trade-offs. Both mild cold and heat shocks led to improved heat tolerance in both sexes. It could be that both mild shocks lead to the expression of heat shock proteins, enhancing heat tolerance in the short run. Cold tolerance was not affected by previous mild cold shock, suggesting that such a cold shock, as a single event, causes little stress and hence elicits only weak physiological reaction. However, previous mild heat stress led to improved cold tolerance but only in males. Our results point to both hardening and cross-tolerance between cold and heat shocks.

  1. The negative effect of starvation and the positive effect of mild thermal stress on thermal tolerance of the red flour beetle, Tribolium castaneum

    Science.gov (United States)

    Scharf, Inon; Wexler, Yonatan; MacMillan, Heath Andrew; Presman, Shira; Simson, Eddie; Rosenstein, Shai

    2016-04-01

    The thermal tolerance of a terrestrial insect species can vary as a result of differences in population origin, developmental stage, age, and sex, as well as via phenotypic plasticity induced in response to changes in the abiotic environment. Here, we studied the effects of both starvation and mild cold and heat shocks on the thermal tolerance of the red flour beetle, Tribolium castaneum. Starvation led to impaired cold tolerance, measured as chill coma recovery time, and this effect, which was stronger in males than females, persisted for longer than 2 days but less than 7 days. Heat tolerance, measured as heat knockdown time, was not affected by starvation. Our results highlight the difficulty faced by insects when encountering multiple stressors simultaneously and indicate physiological trade-offs. Both mild cold and heat shocks led to improved heat tolerance in both sexes. It could be that both mild shocks lead to the expression of heat shock proteins, enhancing heat tolerance in the short run. Cold tolerance was not affected by previous mild cold shock, suggesting that such a cold shock, as a single event, causes little stress and hence elicits only weak physiological reaction. However, previous mild heat stress led to improved cold tolerance but only in males. Our results point to both hardening and cross-tolerance between cold and heat shocks.

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

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    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

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

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    Sergiu Dalm

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

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

    Institute of Scientific and Technical Information of China (English)

    Gonglin Hou; Mingming Tang

    2011-01-01

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

  5. 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...... studies supported perceived stress and distress as risk factors for the development of DM2 among men, but not among women, while WS was generally not supported as a risk factor among neither men nor women; iv) hypertension: marital stress and perceived stress might have an influence on blood pressure (BP......), while no association was found regarding distress. Evaluating WS the results were equivocal and indicated that different types of WS affected the BP differently between men and women. In conclusion, a longitudinal association between chronic psychosocial stress and the development of MES seems present...

  6. 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.

  7. Early adversity contributes to chronic stress induced depression-like behavior in adolescent male rhesus monkeys.

    Science.gov (United States)

    Zhang, Zhi-Yi; Mao, Yu; Feng, Xiao-Li; Zheng, Na; Lü, Long-Bao; Ma, Yuan-Ye; Qin, Dong-Dong; Hu, Xin-Tian

    2016-06-01

    Chronic stress is an important cause for depression. However, not everyone who is exposed to chronic stress will develop depression. Our previous studies demonstrated that early adversity can cause lasting changes in adolescent rhesus monkeys, but depressive symptoms have not been observed. Compared to adults, it is still unknown that whether adolescent rhesus monkeys experiencing early adversity are more likely to develop depressive symptoms. In this study, we investigated the long term relationship between early adversity, chronic stress and adolescent depression for the first time. Eight male rhesus monkeys were reared in maternal separation (MS) or mother-reared (MR) conditions. All of them went through unpredictable chronic stress for two months at their age four. The stressors included space restriction, intimidation, long illumination and fasting. Behavioral and physiological data were collected during the experiment. The results showed that, compared with the MR group, the locomotor activity of MS group was significantly decreased after one month of chronic stress while huddling up and stereotypical behaviors were significantly increased. Moreover, this trend continued and even worsened at the second month. Significantly higher hair cortisol levels and lower body weight were observed in MS group after two months of stress. These results indicate that early adversity is one of the environmental factors which can increase the susceptibility of depression when experiencing chronic stress in the later life. This will further clarify the important roles of early environmental factors in the development of adolescent depression and children rearing conditions should receive more attention.

  8. 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.

  9. Mental Strain and Chronic Stress among University Students with Symptoms of Irritable Bowel Syndrome

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    Marco D. Gulewitsch

    2013-01-01

    Full Text Available 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. Beyond this, IBS subtypes, IBS severity, and health care utilization were assessed. Results. Students fulfilling IBS criteria showed significantly elevated values of mental strain and chronic stress. Nearly 40% of the IBS group (versus 20% of the controls reached a clinically relevant value on the SCL-90-R global severity scale. IBS subtypes did not differ in terms of mental distress or chronic stress. Somatization, anxiety, and the chronic stressors “work overload,” “social tension,” and “dissatisfaction with job” were most closely connected to IBS symptom severity. Regarding health care utilization, our results show that consulting a physician frequently was not associated significantly with elevated mental strain or chronic stress but with IBS symptom severity. Conclusion. Our data contribute additional evidence to the distinct association between psychological stress and IBS in community samples.

  10. Subchronic and mild social defeat stress accelerates food intake and body weight gain with polydipsia-like features in mice.

    Science.gov (United States)

    Goto, Tatsuhiko; Kubota, Yoshifumi; Tanaka, Yuki; Iio, Wataru; Moriya, Naoko; Toyoda, Atsushi

    2014-08-15

    Development and characterization of animal models of depression are essential for fully understanding the pathogenesis of depression in humans. We made and analyzed a mouse model exhibiting social deficit and hyperphagia-like behavior using a subchronic and mild social defeat stress (sCSDS) paradigm. The body weight, food and water intake of mice were monitored during a test period, and their behaviors and serum components were analyzed at two stages: immediately after the sCSDS period and 1 month after the sCSDS. The body weight and food intake of defeated mice were significantly higher than control mice at the sCSDS period, and these differences were sustained until 1 month after the sCSDS, whereas the water intake of defeated mice was significantly higher than control mice for the period of sCSDS only. Behavioral analyses revealed that the defeated mice exhibit significant social aversion to unfamiliar mice in a social interaction test and a trend of anxiety-like behavior in an elevated-plus maze test. Possibly due to polydipsia-like symptoms, defeated mice had significantly lower levels of albumin and blood urea nitrogen than control mice immediately after the sCSDS period but not at 1 month after sCSDS. The present study revealed that our sCSDS mice keep much more water in their body than control mice. This study reports the first step toward an understanding of the mechanisms of stress-induced overhydration, over-eating and resultant weight gain.

  11. Effects of Dalteparin on Structure of Hippocampal Neurons of Rats in Chronic Stress

    OpenAIRE

    Mansoureh Soleimani; Arezo Nahavandi; Fereshteh Farajdokht

    2012-01-01

    Introduction: Stress is defined as any environmental change that disturbs the maintenance of brain homeostasis. Stress leads to production of pro-inflammatory cytokines that provoke rodegenerative disorders. In the present study, we investigated the effects of dalteparin on hippocampal neuronal death induced by chronic stress in rats.Methods : the study was carried out on 60 adult male wistar rats, weighing 200-250 gr. The rats were randomly divided into three groups: control, stress and stre...

  12. [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.

  13. Prone position prevents regional alveolar hyperinflation and mechanical stress and strain in mild experimental acute lung injury.

    Science.gov (United States)

    Santana, Maria Cristina E; Garcia, Cristiane S N B; Xisto, Débora G; Nagato, Lilian K S; Lassance, Roberta M; Prota, Luiz Felipe M; Ornellas, Felipe M; Capelozzi, Vera L; Morales, Marcelo M; Zin, Walter A; Pelosi, Paolo; Rocco, Patricia R M

    2009-06-30

    Prone position may delay the development of ventilator-induced lung injury (VILI), but the mechanisms require better elucidation. In experimental mild acute lung injury (ALI), arterial oxygen partial pressure (Pa O2), lung mechanics and histology, inflammatory markers [interleukin (IL)-6 and IL-1 beta], and type III procollagen (PCIII) mRNA expressions were analysed in supine and prone position. Wistar rats were randomly divided into two groups. In controls, saline was intraperitoneally injected while ALI was induced by paraquat. After 24-h, the animals were mechanically ventilated for 1-h in supine or prone positions. In ALI, prone position led to a better blood flow/tissue ratio both in ventral and dorsal regions and was associated with a more homogeneous distribution of alveolar aeration/tissue ratio reducing lung static elastance and viscoelastic pressure, and increasing end-expiratory lung volume and Pa O2. PCIII expression was higher in the ventral than dorsal region in supine position, with no regional changes in inflammatory markers. In conclusion, prone position may protect the lungs against VILI, thus reducing pulmonary stress and strain.

  14. Enhanced drought tolerance of a soil-dwelling springtail by pre-acclimation to a mild drought stress.

    Science.gov (United States)

    Sjursen, H; Bayley, M; Holmstrup, M

    2001-09-01

    The springtail Folsomia candida has a highly permeable cuticle, but is able to survive several weeks at 98.2%RH. This corresponds to a water potential deficit of about 17bars between the environment and the normal osmotic pressure of the body fluids of this animal. Recent studies have shown a water vapour absorption mechanism by accumulation of sugars and polyols (SP) in F. candida, which explains how this species can survive dehydrating conditions. In the present study, adult F. candida were pre-acclimated at 98.2%RH to induce the accumulation of SP, and were subsequently exposed for additional desiccating conditions from 98 to 94%RH. Activity level, water content, osmotic pressure of body fluids and SP composition were investigated. After the desiccation period, the animals were rehydrated at 100%RH and survival was assessed. The results showed that F. candida survived a more severe drought stress when it had been pre-acclimated to 98.2%RH before exposure to lower humidity. This species was able to maintain hyperosmosity to the surroundings at 95.5%RH, suggesting that it can absorb water vapour down to this limit. Below this limit, trehalose levels increased while myo-inositol levels decreased. We propose that this is a change of survival strategy where F. candida at mild desiccation levels seek to retain water by colligative means (remain hyperosmotic), but at severe desiccation levels switches to an anhydrobiotic strategy.

  15. Chronic Mild Cold Conditioning Modulates the Expression of Hypothalamic Neuropeptide and Intermediary Metabolic-Related Genes and Improves Growth Performances in Young Chicks.

    Directory of Open Access Journals (Sweden)

    Phuong Nguyen

    Full Text Available Low environmental temperatures are among the most challenging stressors in poultry industries. Although landmark studies using acute severe cold exposure have been conducted, still the molecular mechanisms underlying cold-stress responses in birds are not completely defined. In the present study we determine the effect of chronic mild cold conditioning (CMCC on growth performances and on the expression of key metabolic-related genes in three metabolically important tissues: brain (main site for feed intake control, liver (main site for lipogenesis and muscle (main site for thermogenesis.80 one-day old male broiler chicks were divided into two weight-matched groups and maintained in two different temperature floor pen rooms (40 birds/room. The temperature of control room was 32°C, while the cold room temperature started at 26.7°C and gradually reduced every day (1°C/day to reach 19.7°C at the seventh day of the experiment. At day 7, growth performances were recorded (from all birds and blood samples and tissues were collected (n = 10. The rest of birds were maintained at the same standard environmental condition for two more weeks and growth performances were measured.Although feed intake remained unchanged, body weight gain was significantly increased in CMCC compared to the control chicks resulting in a significant low feed conversion ratio (FCR. Circulating cholesterol and creatine kinase levels were higher in CMCC chicks compared to the control group (P<0.05. CMCC significantly decreased the expression of both the hypothalamic orexigenic neuropeptide Y (NPY and anorexigenic cocaine and amphetamine regulated transcript (CART in chick brain which may explain the similar feed intake between the two groups. Compared to the control condition, CMCC increased the mRNA abundance of AMPKα1/α2 and decreased mTOR gene expression (P<0.05, the master energy and nutrient sensors, respectively. It also significantly decreased the expression of fatty

  16. 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.

  17. 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

  18. The total flavonoids extracted from Xiaobuxin Tang reverse the hyperactivity of hypothalamic-pituitary-adrenal axis in chronically stressed rats

    Institute of Scientific and Technical Information of China (English)

    AN Lei; ZHANG You-zhi

    2008-01-01

    Objective To investigate the effect of XBXT-2 on the activity of hypothalamic-pituitary-adrenal (HPA) axis in chronic mild stress (CMS) model of rats. Methods Using ELISA to test the serum corticos-terone, adrenocorticotropic hormone (ACTH) and corticotropin-releasing hormone (CRH) level in CMS rats; Using western blot to determine hippocampal glucocorticoids receptors (GR) expression in CMS rats. Results Co-administration of XBXT-2 (25, 50 mg·kg-1, p. o., 28 days, the effective doses for behavioral responses) significantly decreased the serum corticosterone and ACTH level in CMS rats, while the CRH level was not markedly affected by chronic stress or drugs. Moreover, XBXT-2 significantly increased the GR expression in the hippocampus of CMS rats. The same effects were observed in the positive control drug imipramine ( 10 mg·kg-1 p. o. ). Conclusions The decrease of serum corticosterone and ACTH level, as well as the increase of hippocampal GR expression may be the mechanisms underlying the antidepressant action of XBXT-2, which may associate with HPA axis.

  19. Oxidative stress and Kawasaki disease: how is oxidative stress involved from the acute stage to the chronic stage?

    Science.gov (United States)

    Yahata, Tomoyo; Hamaoka, Kenji

    2017-01-01

    Inflammation and oxidative stress are closely related. Further, oxidative stress plays an important role in the pathology of inflammation-based Kawasaki disease. An excessive in vivo production of reactive oxygen species increases oxidative stress in the body, which triggers an endless vicious spiral of inflammation reactions and reactive oxygen metabolites. This presumably forms diffuse vasculitis in the acute phase. Acute inflammation and oxidative stress can be rapidly controlled by treatments; however, they may remain for a long time. This has recently been identified as a problem in the chronic phase of Kawasaki disease. Generally, the presence of vascular inflammation and oxidative stress impairs blood vessels, leading to the onset of atherosclerosis, which is a widely recognized risk. The current discussion focuses on whether the same is valid for blood vessels in the chronic phase of Kawasaki disease.

  20. Brain-derived neurotrophic factor signalling mediates the antidepressant-like effect of piperine in chronically stressed mice.

    Science.gov (United States)

    Mao, Qing-Qiu; Huang, Zhen; Zhong, Xiao-Ming; Xian, Yan-Fang; Ip, Siu-Po

    2014-03-15

    Previous studies in our laboratory have demonstrated that piperine produced antidepressant-like action in various mouse models of behavioral despair. This study aimed to investigate the role of brain-derived neurotrophic factor (BDNF) signalling in the antidepressant-like effect of piperine in mice exposed to chronic unpredictable mild stress (CUMS). The results showed that CUMS caused depression-like behavior in mice, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. It was also found that BDNF protein expression in the hippocampus and frontal cortex were significantly decreased in CUMS-treated mice. Chronic treatment of piperine at the dose of 10mg/kg significantly ameliorated behavioural deficits of CUMS-treated mice in the sucrose preference test and forced swim test. Piperine treatment also significantly decreased immobility time in the forced swim test in naive mice. In parallel, chronic piperine treatment significantly increased BDNF protein expression in the hippocampus and frontal cortex of both naive and CUMS-treated mice. In addition, inhibition of BDNF signalling by injection of K252a, an inhibitor of the BDNF receptor TrkB, significantly blocked the antidepressant-like effect of piperine in the sucrose preference test and forced swim test of CUMS-treated mice. Taken together, this study suggests that BDNF signalling is an essential mediator for the antidepressant-like effect of piperine.

  1. Early predictors of chronic post-traumatic stress disorder in assault survivors

    OpenAIRE

    Kleim, Birgit; Ehlers, Anke; Glucksman, Edward

    2007-01-01

    Background Some studies suggest that early psychological treatment is effective in preventing chronic post-traumatic stress disorder (PTSD), but it is as yet unclear how best to identify trauma survivors who need such intervention. This prospective longitudinal study investigated the prognostic validity of acute stress disorder (ASD), of variables derived from a meta-analysis of risk factors for PTSD, and of candidate cognitive and biological variables in predicting chronic PTSD following ass...

  2. 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.

  3. Effects of (-)-sesamin on chronic stress-induced memory deficits in mice.

    Science.gov (United States)

    Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Kim, Kyung Sook; Lee, Kung Eun; Cho, Yoon Jeong; Lee, Myung Koo

    2016-11-10

    This study investigated the effects of (-)-sesamin on memory deficits induced by chronic electric footshock (EF)-induced stress in mice. Mice were treated with (-)-sesamin (25 and 50mg/kg, p.o., daily for 21day) prior to chronic EF stress (0.6mA, 1s every 5s for 3min, daily for 21day). Transfer retention latencies in the elevated plus maze test and N-methyl-d-aspartate (NMDA) receptor (type 1) phosphorylation in the hippocampus increased with chronic EF stress, and they were reduced by treatment with (-)-sesamin at both doses. Phosphorylation of extracellular signal-regulated kinase (ERK1/2) and cyclic AMP-responsive element binding protein (CREB), which were reduced by chronic EF stress, were increased by treatment with (-)-sesamin. Retention latencies in the passive avoidance test and dopamine levels in the substantia nigra-striatum were also reduced by chronic EF stress, and similarly recovered with (-)-sesamin treatment. These results suggest that (-)-sesamin ameliorates the effects of chronic EF stress-induced spatial and habit learning memory deficits by modulating both NMDA receptor and dopaminergic neuronal systems.

  4. Neurological and cellular regulation of visceral hypersensitivity induced by chronic stress and colonic inflammation in rats.

    Science.gov (United States)

    Chen, J; Winston, J H; Sarna, S K

    2013-09-17

    The role of inflammation in inducing visceral hypersensitivity (VHS) in ulcerative colitis patients remains unknown. We tested the hypothesis that acute ulcerative colitis-like inflammation does not induce VHS. However, it sets up molecular conditions such that chronic stress following inflammation exaggerates single-unit afferent discharges to colorectal distension. We used dextran sodium sulfate (DSS) to induce ulcerative colitis-like inflammation and a 9-day heterotypic chronic stress protocol in rats. DSS upregulated Nav1.8 mRNA in colon-responsive dorsal root ganglion (DRG) neurons, TRPV1 in colonic muscularis externae (ME) and BDNF in spinal cord without affecting the spike frequency in spinal afferents or VMR to CRD. By contrast, chronic stress did not induce inflammation but it downregulated Kv1.1 and Kv1.4 mRNA in DRG neurons, and upregulated TRPA1 and nerve growth factor in ME, which mediated the increase of spike frequency and VMR to CRD. Chronic stress following inflammation exacerbated spike frequency in spinal afferent neurons. TRPA1 antagonist suppressed the sensitization of afferent neurons. DSS-inflammation did not affect the composition or excitation thresholds of low-threshold and high-threshold fibers. Chronic stress following inflammation increased the percent composition of high-threshold fibers and lowered the excitation threshold of both types of fibers. We conclude that not all types of inflammation induce VHS, whereas chronic stress induces VHS in the absence of inflammation.

  5. Controlled Low-Pressure Blast-Wave Exposure Causes Distinct Behavioral and Morphological Responses Modelling Mild Traumatic Brain Injury, Post-Traumatic Stress Disorder, and Comorbid Mild Traumatic Brain Injury-Post-Traumatic Stress Disorder.

    Science.gov (United States)

    Zuckerman, Amitai; Ram, Omri; Ifergane, Gal; Matar, Michael A; Sagi, Ram; Ostfeld, Ishay; Hoffman, Jay R; Kaplan, Zeev; Sadot, Oren; Cohen, Hagit

    2017-01-01

    The intense focus in the clinical literature on the mental and neurocognitive sequelae of explosive blast-wave exposure, especially when comorbid with post-traumatic stress-related disorders (PTSD) is justified, and warrants the design of translationally valid animal studies to provide valid complementary basic data. We employed a controlled experimental blast-wave paradigm in which unanesthetized animals were exposed to visual, auditory, olfactory, and tactile effects of an explosive blast-wave produced by exploding a thin copper wire. By combining cognitive-behavioral paradigms and ex vivo brain MRI to assess mild traumatic brain injury (mTBI) phenotype with a validated behavioral model for PTSD, complemented by morphological assessments, this study sought to examine our ability to evaluate the biobehavioral effects of low-intensity blast overpressure on rats, in a translationally valid manner. There were no significant differences between blast- and sham-exposed rats on motor coordination and strength, or sensory function. Whereas most male rats exposed to the blast-wave displayed normal behavioral and cognitive responses, 23.6% of the rats displayed a significant retardation of spatial learning acquisition, fulfilling criteria for mTBI-like responses. In addition, 5.4% of the blast-exposed animals displayed an extreme response in the behavioral tasks used to define PTSD-like criteria, whereas 10.9% of the rats developed both long-lasting and progressively worsening behavioral and cognitive "symptoms," suggesting comorbid PTSD-mTBI-like behavioral and cognitive response patterns. Neither group displayed changes on MRI. Exposure to experimental blast-wave elicited distinct behavioral and morphological responses modelling mTBI-like, PTSD-like, and comorbid mTBI-PTSD-like responses. This experimental animal model can be a useful tool for elucidating neurobiological mechanisms underlying the effects of blast-wave-induced mTBI and PTSD and comorbid mTBI-PTSD.

  6. Saikokaryukotsuboreito, a herbal medicine, prevents chronic stress-induced anxiety in rats: comparison with diazepam.

    Science.gov (United States)

    Mizoguchi, Kazushige; Ikeda, Ryuji; Shoji, Hirotaka; Tanaka, Yayoi; Jin, Xue-Long; Kase, Yoshio; Takeda, Shuichi; Maruyama, Wakako; Tabira, Takeshi

    2009-01-01

    Anxiety is frequently observed in several neuropsychiatric disorders, and stress is thought to precipitate or exacerbate anxiety. In this study, the anxiolytic action of a herbal medicine, saikokaryukotsuboreito, (SRBT) was examined in normal healthy rats using the elevated plus-maze test. Moreover, the improving effect of SRBT on chronic stress-induced anxiety was also examined. Single administration of SRBT did not have anxiolytic action in normal rats. Repeated administration of SRBT significantly improved chronic stress-induced anxiety. On the other hand, single administration of a typical anxiolytic, diazepam, had anxiolytic action in normal rats but repeated administration did not improve chronic stress-induced anxiety. These results suggest that SRBT does not have anxiolytic activity equivalent to that of diazepam but has potency for improving stress-related anxiety. This finding provides information important for the treatment of anxiety.

  7. 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.

  8. 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.

  9. Chronic administration of fluoxetine or clozapine induces oxidative stress in rat liver: a histopathological study.

    Science.gov (United States)

    Zlatković, Jelena; Todorović, Nevena; Tomanović, Nada; Bošković, Maja; Djordjević, Snežana; Lazarević-Pašti, Tamara; Bernardi, Rick E; Djurdjević, Aleksandra; Filipović, Dragana

    2014-08-01

    Chronic exposure to stress contributes to the etiology of mood disorders, and the liver as a target organ of antidepressant and antipsychotic drug metabolism is vulnerable to drug-induced toxicity. We investigated the effects of chronic administration of fluoxetine (15mg/kg/day) or clozapine (20mg/kg/day) on liver injury via the measurement of liver enzymes, oxidative stress and histopathology in rats exposed to chronic social isolation (21days), an animal model of depression, and controls. The activity of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST), the liver content of carbonyl groups, malonyldialdehyde (MDA), reduced glutathione (GSH), cytosolic glutathione S-transferase (GST) and nitric oxide (NO) metabolites were determined. We also characterized nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2) and CuZn-superoxide dismutase (CuZnSOD) protein expression as well as histopathological changes. Increased serum ALT activity in chronically-isolated and control animals treated with both drugs was found while increased AST activity was observed only in fluoxetine-treated rats (chronically-isolated and controls). Increased carbonyl content, MDA, GST activity and decreased GSH levels in drug-treated controls/chronically-isolated animals suggest a link between drugs and hepatic oxidative stress. Increased NO levels associated with NF-κB activation and the concomitant increased COX-2 expression together with compromised CuZnSOD expression in clozapine-treated chronically-isolated rats likely reinforce oxidative stress, observed by increased lipid peroxidation and GSH depletion. In contrast, fluoxetine reduced NO levels in chronically-isolated rats. Isolation induced oxidative stress but histological changes were similar to those observed in vehicle-treated controls. Chronic administration of fluoxetine in both chronically-isolated and control animals resulted in more or less normal hepatic architecture, while clozapine in both groups

  10. Understanding sequelae of injury mechanisms and mild traumatic brain injury incurred during the conflicts in Iraq and Afghanistan: persistent postconcussive symptoms and posttraumatic stress disorder.

    Science.gov (United States)

    Schneiderman, Aaron I; Braver, Elisa R; Kang, Han K

    2008-06-15

    A cross-sectional study of military personnel following deployment to conflicts in Iraq or Afghanistan ascertained histories of combat theater injury mechanisms and mild traumatic brain injury (TBI) and current prevalence of posttraumatic stress disorder (PTSD) and postconcussive symptoms. Associations among injuries, PTSD, and postconcussive symptoms were explored. In February 2005, a postal survey was sent to Iraq/Afghanistan veterans who had left combat theaters by September 2004 and lived in Maryland; Washington, DC; northern Virginia; and eastern West Virginia. Immediate neurologic symptoms postinjury were used to identify mild TBI. Adjusted prevalence ratios and 95% confidence intervals were computed by using Poisson regression. About 12% of 2,235 respondents reported a history consistent with mild TBI, and 11% screened positive for PTSD. Mild TBI history was common among veterans injured by bullets/shrapnel, blasts, motor vehicle crashes, air/water transport, and falls. Factors associated with PTSD included reporting multiple injury mechanisms (prevalence ratio = 3.71 for three or more mechanisms, 95% confidence interval: 2.23, 6.19) and combat mild TBI (prevalence ratio = 2.37, 95% confidence interval: 1.72, 3.28). The strongest factor associated with postconcussive symptoms was PTSD, even after overlapping symptoms were removed from the PTSD score (prevalence ratio = 3.79, 95% confidence interval: 2.57, 5.59).

  11. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury

    OpenAIRE

    Radouil Tzekov; Clint Dawson; Megan Orlando; Benoit Mouzon; Jon Reed; James Evans; Gogce Crynen; Michael Mullan; Fiona Crawford

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue w...

  12. 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.

  13. Transcriptome, carbohydrate and phytohormone analysis of Petunia hybrida reveals a complex disturbance of plant functional integrity under mild chilling stress

    Directory of Open Access Journals (Sweden)

    Martin Andreas Bauerfeind

    2015-07-01

    Full Text Available Cultivation of chilling-tolerant ornamental crops at lower temperature could reduce the energy demands of heated greenhouses. To provide a better understanding of how sub-optimal temperatures (12°C vs. 16°C affect growth of the sensitive Petunia hybrida cultivar `SweetSunshine Williams´, the transcriptome, carbohydrate metabolism and phytohormone homeostasis were monitored in aerial plant parts over four weeks by use of a microarray, enzymatic assays and GC-MS/MS. The data revealed three consecutive phases of chilling response. The first days were marked by a strong accumulation of sugars, particularly in source leaves, preferential up-regulation of genes in the same tissue and down-regulation of several genes in the shoot apex, especially those involved in the abiotic stress response. The midterm phase featured a partial normalization of carbohydrate levels and gene expression. After three weeks of chilling exposure, a new stabilized balance was established. Reduced hexose levels in the shoot apex, reduced ratios of sugar levels between the apex and source leaves and a higher apical sucrose/hexose ratio, associated with decreased activity and expression of cell wall invertase, indicate that prolonged chilling induced sugar accumulation in source leaves at the expense of reduced sugar transport to and reduced sucrose utilization in the shoot. This was associated with reduced levels of indole-3-acetic acid and abscisic acid in the apex and high numbers of differentially, particularly up-regulated genes, especially in the source leaves, including those regulating histones, ethylene action, transcription factors and a jasmonate-ZIM-domain protein. Transcripts of one Jumonji C domain containing protein and one expansin accumulated in source leaves throughout the chilling period. The results reveal a dynamic and complex disturbance of plant function in response to mild chilling, opening new perspectives for the comparative analysis of differently

  14. 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

  15. 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)

  16. 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...

  17. Protective Effect of Self-Compassion to Emotional Response among Students with Chronic Academic Stress.

    Science.gov (United States)

    Zhang, Yonghong; Luo, Xi; Che, Xianwei; Duan, Wenjie

    2016-01-01

    The literature has shown that self-compassion is a protective factor of an individual's emotional response to chronic stress. However, this stress-buffering effect has not been completely analyzed in individuals who report significantly high academic stress. The present study explored the role of self-compassion in a group of undergraduate students who experience chronic academic stress. A total of 208 undergraduate students who were preparing for the Postgraduate Entrance Examination (PEE) were recruited and completed the Self-Compassion Scale, Adolescent Self-Rating Life Event Check List, and Positive and Negative Affect Schedule. Differences analysis confirmed that the participants reported significantly higher academic stress than their peers who were not preparing for PEE. Self-compassion positively related to positive affect but negatively related to negative affect and learning stress. Further analysis showed that self-compassion negatively mediated the relationship between chronic academic stress and negative affect. Findings imply that self-compassion-centered interventions can be developed in the educational context to assist students cope with chronic academic stress.

  18. 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)

  19. Brief treatment with the glucocorticoid receptor antagonist mifepristone normalizes the reduction in neurogenesis after chronic stress.

    NARCIS (Netherlands)

    Oomen, C.A.; Mayer, J.L.; de Kloet, E.R.; Joëls, M.; Lucassen, P.J.

    2007-01-01

    In rodents, stress suppresses adult neurogenesis. This is thought to involve activation of glucocorticoid receptors in the brain. In the present study, we therefore questioned whether glucocorticoid receptor blockade by mifepristone can normalize the effects of chronic stress on adult neurogenesis.

  20. Protective Effect of Self-compassion to Emotional Response among Students with Chronic Academic Stress

    Directory of Open Access Journals (Sweden)

    Yonghong Zhang

    2016-11-01

    Full Text Available The literature has shown that self-compassion is a protective factor of an individual’s emo-tional response to chronic stress. However, this stress-buffering effect has not been complete-ly analyzed in individuals who report significantly high academic stress. The present study explored the role of self-compassion in a group of undergraduate students who experience chronic academic stress. A total of 208 undergraduate students who were preparing for the Postgraduate Entrance Examination (PEE were recruited and completed the Self-Compassion Scale, Adolescent Self-Rating Life Event Check List, and Positive and Negative Affect Schedule. Differences analysis confirmed that the participants reported significantly higher academic stress than their peers who were not preparing for PEE. Self-compassion positively related to positive affect but negatively related to negative affect and learning stress. Further analysis showed that self-compassion negatively mediated the relationship be-tween chronic academic stress and negative affect. Findings imply that self-compassion-centered interventions can be developed in the educational context to assist students cope with chronic academic stress.

  1. 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...

  2. 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…

  3. Accelerated Aging during Chronic Oxidative Stress: A Role for PARP-1

    Directory of Open Access Journals (Sweden)

    Daniëlle M. P. H. J. Boesten

    2013-01-01

    Full Text Available Oxidative stress plays a major role in the pathophysiology of chronic inflammatory disease and it has also been linked to accelerated telomere shortening. Telomeres are specialized structures at the ends of linear chromosomes that protect these ends from degradation and fusion. Telomeres shorten with each cell division eventually leading to cellular senescence. Research has shown that poly(ADP-ribose polymerase-1 (PARP-1 and subtelomeric methylation play a role in telomere stability. We hypothesized that PARP-1 plays a role in accelerated aging in chronic inflammatory diseases due to its role as coactivator of NF-κb and AP-1. Therefore we evaluated the effect of chronic PARP-1 inhibition (by fisetin and minocycline in human fibroblasts (HF cultured under normal conditions and under conditions of chronic oxidative stress, induced by tert-butyl hydroperoxide (t-BHP. Results showed that PARP-1 inhibition under normal culturing conditions accelerated the rate of telomere shortening. However, under conditions of chronic oxidative stress, PARP-1 inhibition did not show accelerated telomere shortening. We also observed a strong correlation between telomere length and subtelomeric methylation status of HF cells. We conclude that chronic PARP-1 inhibition appears to be beneficial in conditions of chronic oxidative stress but may be detrimental under relatively normal conditions.

  4. Quantification of the impact of single and multiple mild stresses on outgrowth heterogeneity of Bacillus cereus spores.

    Science.gov (United States)

    van Melis, C C J; den Besten, H M W; Nierop Groot, M N; Abee, T

    2014-05-02

    Outgrowth heterogeneity of bacterial spore populations complicates both prediction and efficient control of spore outgrowth. In this study, the impact of mild preservation stresses on outgrowth of Bacillus cereus ATCC 14579 spores was quantified during the first stages of outgrowth. Heterogeneity in outgrowth of heat-treated (90°C for 10 min) and non-heat-treated germinated single spores to the maximum micro-colony stage of 256 cells was assessed by direct imaging on Anopore strips, placed on BHI plates at pH7 and pH5.5, without and with added NaCl or sorbic acid (HSA). At pH7 non-heated and heat-treated germinated spores required 6h to reach the maximum microcolony stage with limited heterogeneity, and these parameters were only slightly affected with both types of spores when incubated at pH7 with added NaCl. Notably, the most pronounced effects were observed during outgrowth of spores at pH5.5 without and with added NaCl or HSA. Non-heat-treated germinated spores showed again efficient outgrowth with limited heterogeneity reaching the maximum microcolony stage after 6h at pH5.5, which increased to 12h and 16 h with added NaCl and HSA, respectively. In contrast, heat-treated spores displayed a strong delay between initial germination and swelling and further outgrowth at pH5.5, resulting in large heterogeneity and low numbers of fastest growers reaching the maximum microcolony stage after 10, 12 and 24h, without and with added NaCl or HSA, respectively. This work shows that Anopore technology provides quantitative information on the impact of combined preservation stresses on outgrowth of single spores, showing that outgrowth of germinated heat-treated spores is significantly affected at pH5.5 with a large fraction of spores arrested in the early outgrowth stage, and with outgrowing cells showing large heterogeneity with only a small fraction committed to relatively fast outgrowth.

  5. Chronic stress reduces the number of GABAergic interneurons in the adult rat hippocampus, dorsal-ventral and region-specific differences.

    Science.gov (United States)

    Czéh, Boldizsár; Varga, Zsófia K Kalangyáné; Henningsen, Kim; Kovács, Gábor L; Miseta, Attila; Wiborg, Ove

    2015-03-01

    Major depressive disorder is a common and complex mental disorder with unknown etiology. GABAergic dysfunction is likely to contribute to the pathophysiology since disrupted GABAergic systems are well documented in depressed patients. Here we studied structural changes in the hippocampal GABAergic network using the chronic mild stress (CMS) model, as one of the best validated animal models for depression. Rats were subjected to 9 weeks of daily stress and behaviorally characterized using the sucrose consumption test into anhedonic and resilient animals based on their response to stress. Different subtypes of GABAergic interneurons were visualized by immunohistochemistry using antibodies for parvalbumin (PV), calretinin (CR), calbindin (CB), cholecystokinin (CCK), somatostatin (SOM), and neuropeptide Y (NPY). We used an unbiased quantification method to systematically count labeled cells in different subareas of the dorsal and ventral hippocampus. Chronic stress reduced the number of specific interneurons in distinct hippocampal subregions significantly. PV+ and CR+ neurons were reduced in all dorsal subareas, whereas in the ventral part only the CA1 was affected. Stress had the most pronounced effect on the NPY+ and SOM+ cells and reduced their number in almost all dorsal and ventral subareas. Stress had no effect on the CCK+ and CB+ interneurons. In most cases the effect of stress was irrespective to the behavioral phenotype. However, in a few specific areas the number of SOM+, NPY+, and CR+ neurons were significantly reduced in anhedonic animals compared to the resilient group. Overall, these data clearly demonstrate that chronic stress affects the structural integrity of specific GABAergic neuronal subpopulations and this should also affect the functioning of these hippocampal GABAergic networks.

  6. Effects of acute restraint-induced stress on glucocorticoid receptors and brain-derived neurotrophic factor after mild traumatic brain injury.

    Science.gov (United States)

    Griesbach, G S; Vincelli, J; Tio, D L; Hovda, D A

    2012-05-17

    We have previously reported that experimental mild traumatic brain injury results in increased sensitivity to stressful events during the first post-injury weeks, as determined by analyzing the hypothalamic-pituitary-adrenal (HPA) axis regulation following restraint-induced stress. This is the same time period when rehabilitative exercise has proven to be ineffective after a mild fluid-percussion injury (FPI). Here we evaluated effects of stress on neuroplasticity. Adult male rats underwent either an FPI or sham injury. Additional rats were only exposed to anesthesia. Rats were exposed to 30 min of restraint stress, followed by tail vein blood collection at post-injury days (PID) 1, 7, and 14. The response to dexamethasone (DEX) was also evaluated. Hippocampal tissue was collected 120 min after stress onset. Brain-derived neurotrophic factor (BDNF) along with glucocorticoid (GR) and mineralocorticoid (MR) receptors was determined by Western blot analysis. Results indicated injury-dependent changes in glucocorticoid and mineralocorticoid receptors that were influenced by the presence of dexamethasone. Control and FPI rats responded differentially to DEX in that GR increases after receiving the lower dose of DEX were longer lasting in the FPI group. A suppression of MR was found at PID 1 in vehicle-treated FPI and Sham groups. Decreases in the precursor form of BDNF were observed in different FPI groups at PIDs 7 and 14. These findings suggest that the increased sensitivity to stressful events during the first post-injury weeks, after a mild FPI, has an impact on hippocampal neuroplasticity.

  7. 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.

  8. Preventive and therapeutic effect of treadmill running on chronic stress-induced memory deficit in rats.

    Science.gov (United States)

    Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

    2015-04-01

    Previous results indicated that stress impairs learning and memory. In this research, the effects of preventive, therapeutic and regular continually running activity on chronic stress-induced memory deficit in rats were investigated. 70 male rats were randomly divided into seven groups as follows: Control, Sham, Stress-Rest, Rest-Stress, Stress-Exercise, Exercise-Stress and Exercise-Stress & Exercise groups. Chronic restraint stress was applied 6 h/day for 21days and treadmill running 1 h/day. Memory function was evaluated by the passive avoidance test. The results revealed that running activities had therapeutic effect on mid and long-term memory deficit and preventive effects on short and mid-term memory deficit in stressed rats. Regular continually running activity improved mid and long-term memory compared to Exercise-Stress group. The beneficial effects of exercise were time-dependent in stress conditions. Finally, data corresponded to the possibility that treadmill running had a more important role on treatment rather than on prevention on memory impairment induced by stress.

  9. Hope and fatigue in chronic illness: The role of perceived stress.

    Science.gov (United States)

    Hirsch, Jameson K; Sirois, Fuschia M

    2016-04-01

    Fatigue is a debilitating symptom of chronic illness that is deleteriously affected by perceived stress, a process particularly relevant to inflammatory disease. Hopefulness, a goal-based motivational construct, may beneficially influence stress and fatigue, yet little research has examined these associations. We assessed the relation between hope and fatigue, and the mediating effect of stress, in individuals with fibromyalgia, arthritis, and inflammatory bowel disease. Covarying age, sex, and pain, stress partially mediated the association between hope and fatigue; those with greater hope reported less stress and consequent fatigue. Therapeutically, bolstering hope may allow proactive management of stressors, resulting in less fatigue.

  10. 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.

  11. 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.

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

    Science.gov (United States)

    Outcalt, Samantha D; Ang, Dennis C; Wu, Jingwei; Sargent, Christy; Yu, Zhangsheng; Bair, Matthew J

    2014-01-01

    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.

  13. Long-term effect of inhaled budesonide in mild and moderate chronic obstructive pulmonary disease: a randomised controlled trial

    DEFF Research Database (Denmark)

    Vestbo, Jørgen; Sørensen, T; Lange, Peter;

    1999-01-01

    for 36 months. The mean age of the participants was 59 years and the mean FEV1 2.37 L or 86% of predicted. The main outcome measure was rate of FEV1 decline. Analyses were by intention to treat. FINDINGS: The crude rates of FEV1 decline were slightly smaller than expected (placebo group 41.8 mL per year...... recruited from the general population by screening. We question the role of long-term inhaled corticosteroids in the treatment of mild to moderate COPD....

  14. Chronic stress and coping among cardiac surgeons: a single center study

    Directory of Open Access Journals (Sweden)

    Kyriakos Spiliopoulos

    2014-09-01

    Full Text Available Introduction: Cardiac surgeons stress may impair their quality of life and professional practice. Objective: To assess perceived chronic stress and coping strategies among cardiac surgeons. Methods: Twenty-two cardiac surgeons answered two self-assessment questionnaires, the Trier Inventory for Chronic Stress and the German SGV for coping strategies. Results: Participants mean age was 40±14.1 years and 13 were male; eight were senior physicians and 14 were residents. Mean values for the Trier Inventory for Chronic Stress were within the normal range. Unexperienced physicians had significantly higher levels of dissatisfaction at work, lack of social recognition, and isolation (P<0.05. Coping strategies such as play down, distraction from situation, and substitutional satisfaction were also significantly more frequent among unexperienced surgeons. "Negative" stress-coping strategies occur more often in experienced than in younger colleagues (P=0.029. Female surgeons felt more exposed to overwork (P=0.04 and social stress (P=0.03. Conclusion: Cardiac surgeons show a tendency to high perception of chronic stress phenomena and vulnerability for negative coping strategies.

  15. 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.

  16. 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.

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

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    Linda Sterrenburg

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

  18. 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 ...

  19. Effects of Acute and Chronic Cold Stress on Antioxidant Function in Intestinal Tracts of Chickens

    Institute of Scientific and Technical Information of China (English)

    Xu Ming; Yu Xian-yi; Li Jin-long; Han Yan-hui; Li Shu; Xu Shi-wen

    2012-01-01

    This study was to investigate the effects of cold stress on the contents of total antioxidant capacity (T-AOC) malondialdehyde (MDA) and superoxide dismutase (SOD) in duodenum, jejunum and ileum of chickens. A total of 80 15-dayold male chickens were treated by cold stress with the duration of the acute cold stress being 1, 3, 6, 12, and 24 h, and the chronic cold stress was 5, 10, and 20 days, respectively. Cold stress temperature was (12±1)℃. The chemical colorimetric method was used to detect the changes of the T-AOC, SOD activities and MDA contents. The results showed that compared with the corresponding control group, effects of acute cold stress on the T-AOC in duodenum, jejunum and ileum of chickens significantly (P〈0.05) increased firstly and then decreased. Under chronic cold stress, the T-AOC significantly (P〈0.05) decreased. Under acute cold stress and chronic cold stress, the MDA contents significantly (P〈0.05) increased in duodenum, jejunum and ileum of chickens. The effects of acute cold stress on the SOD activities in duodenum, jejunum and ileum of chickens significantly (P〈0.05) increased firstly and then decreased Under chronic cold stress the SOD activities significantly (P〈0.05) decreased in jejunum and ileum, but significantly (P〈0.05) decreased firstly and then increased in duodenum.

  20. Effect of mild-to-moderate smoking on viral load, cytokines, oxidative stress, and cytochrome P450 enzymes in HIV-infected individuals.

    Directory of Open Access Journals (Sweden)

    Anusha Ande

    Full Text Available Mild-to-moderate tobacco smoking is highly prevalent in HIV-infected individuals, and is known to exacerbate HIV pathogenesis. The objective of this study was to determine the specific effects of mild-to-moderate smoking on viral load, cytokine production, and oxidative stress and cytochrome P450 (CYP pathways in HIV-infected individuals who have not yet received antiretroviral therapy (ART. Thirty-two human subjects were recruited and assigned to four different cohorts as follows: a HIV negative non-smokers, b HIV positive non-smokers, c HIV negative mild-to-moderate smokers, and d HIV positive mild-to-moderate smokers. Patients were recruited in Cameroon, Africa using strict selection criteria to exclude patients not yet eligible for ART and not receiving conventional or traditional medications. Those with active tuberculosis, hepatitis B or with a history of substance abuse were also excluded. Our results showed an increase in the viral load in the plasma of HIV positive patients who were mild-to-moderate smokers compared to individuals who did not smoke. Furthermore, although we did not observe significant changes in the levels of most pro-inflammatory cytokines, the cytokine IL-8 and MCP-1 showed a significant decrease in the plasma of HIV-infected patients and smokers compared with HIV negative non-smokers. Importantly, HIV-infected individuals and smokers showed a significant increase in oxidative stress compared with HIV negative non-smoker subjects in both plasma and monocytes. To examine the possible pathways involved in increased oxidative stress and viral load, we determined the mRNA levels of several antioxidant and cytochrome P450 enzymes in monocytes. The results showed that the levels of most antioxidants are unaltered, suggesting their inability to counter oxidative stress. While CYP2A6 was induced in smokers, CYP3A4 was induced in HIV and HIV positive smokers compared with HIV negative non-smokers. Overall, the findings suggest

  1. 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.

  2. Effect of individually tailored biopsychosocial workplace interventions on chronic musculoskeletal pain and stress among laboratory technicians

    DEFF Research Database (Denmark)

    Andersen, Kenneth Jay; Brandt, Mikkel; Hansen, Klaus

    2015-01-01

    BACKGROUND: Chronic musculoskeletal pain is prevalent among laboratory technicians and work-related stress may aggravate the problem. OBJECTIVES: This study investigated the effect of a multifaceted worksite intervention on pain and stress among laboratory technicians with chronic musculoskeletal...... pain using individually tailored physical and cognitive elements. STUDY DESIGN: This trial uses a single-blind randomized controlled design with allocation concealment in a 2-armed parallel group format among laboratory technicians. The trial "Implementation of physical exercise at the Workplace (IRMA......: neck, shoulder, lower and upper back, elbow, and hand at 10 week follow-up. The secondary outcome measure was stress assessed by Cohen´s perceived stress questionnaire. In addition, an explorative dose-response analysis was performed on the adherence to PCMT with pain and stress, respectively...

  3. Selected Cytokines Serve as Potential Biomarkers for Predicting Liver Inflammation and Fibrosis in Chronic Hepatitis B Patients With Normal to Mildly Elevated Aminotransferases.

    Science.gov (United States)

    Deng, Yong-Qiong; Zhao, Hong; Ma, An-Lin; Zhou, Ji-Yuan; Xie, Shi-Bin; Zhang, Xu-Qing; Zhang, Da-Zhi; Xie, Qing; Zhang, Guo; Shang, Jia; Cheng, Jun; Zhao, Wei-Feng; Zou, Zhi-Qiang; Zhang, Ming-Xiang; Wang, Gui-Qiang

    2015-11-01

    Previous studies of small cohorts have implicated several circulating cytokines with progression of chronic hepatitis B (CHB). However, to date there have been no reliable biomarkers for assessing histological liver damage in CHB patients with normal or mildly elevated alanine aminotransferase (ALT). The aim of the present study was to investigate the association between circulating cytokines and histological liver damage in a large cohort. Also, this study was designed to assess the utility of circulating cytokines in diagnosing liver inflammation and fibrosis in CHB patients with ALT less than 2 times the upper limit of normal range (ULN). A total of 227 CHB patients were prospectively enrolled. All patients underwent liver biopsy and staging by Ishak system. Patients with at least moderate inflammation showed significantly higher levels of CXCL-11, CXCL-10, and interleukin (IL)-2 receptor (R) than patients with less than moderate inflammation (P inflammation and significant fibrosis, respectively. Multivariate analysis demonstrated that CXCL-11 was independently associated with at least moderate inflammation, and TGF-α and IL-2R independently correlated with significant fibrosis in patients with ALT inflammation-index and fib-index were developed, which showed areas under the receiver operating characteristics curve (AUROC) of 0.75 (95% CI 0.66-0.84) for at least moderate inflammation and 0.82 (95% CI 0.75-0.90) for significant fibrosis, correspondingly. Compared to existing scores, fib-index was significantly superior to aspartate aminotransferase (AST) to platelet ratio index (APRI) and FIB-4 score for significant fibrosis. In conclusion, CXCL-11 was independently associated with at least moderate inflammation, whereas IL-2R and TGF-α were independent indicators of significant fibrosis in both, total CHB patients and patients with normal or mildly elevated ALT. An IL-2R and TGF-α based score (fib-index) was superior to APRI and FIB-4 for the diagnosis

  4. Blocking metabotropic glutamate receptor subtype 5 relieves maladaptive chronic stress consequences.

    Science.gov (United States)

    Peterlik, Daniel; Stangl, Christina; Bauer, Amelie; Bludau, Anna; Keller, Jana; Grabski, Dominik; Killian, Tobias; Schmidt, Dominic; Zajicek, Franziska; Jaeschke, Georg; Lindemann, Lothar; Reber, Stefan O; Flor, Peter J; Uschold-Schmidt, Nicole

    2017-01-01

    Etiology and pharmacotherapy of stress-related psychiatric conditions and somatoform disorders are areas of high unmet medical need. Stressors holding chronic plus psychosocial components thereby bear the highest health risk. Although the metabotropic glutamate receptor subtype 5 (mGlu5) is well studied in the context of acute stress-induced behaviors and physiology, virtually nothing is known about its potential involvement in chronic psychosocial stress. Using the mGlu5 negative allosteric modulator CTEP (2-chloro-4-[2-[2,5-dimethyl-1-[4-(trifluoromethoxy)phenyl]imidazol-4yl]ethynyl]pyridine), a close analogue of the clinically active drug basimglurant - but optimized for rodent studies, as well as mGlu5-deficient mice in combination with a mouse model of male subordination (termed CSC, chronic subordinate colony housing), we demonstrate that mGlu5 mediates multiple physiological, immunological, and behavioral consequences of chronic psychosocial stressor exposure. For instance, CTEP dose-dependently relieved hypothalamo-pituitary-adrenal axis dysfunctions, colonic inflammation as well as the CSC-induced increase in innate anxiety; genetic ablation of mGlu5 in mice largely reproduced the stress-protective effects of CTEP and additionally ameliorated CSC-induced physiological anxiety. Interestingly, CSC also induced an upregulation of mGlu5 in the hippocampus, a stress-regulating brain area. Taken together, our findings provide evidence that mGlu5 is an important mediator for a wide range of chronic psychosocial stress-induced alterations and a potentially valuable drug target for the treatment of chronic stress-related pathologies in man.

  5. 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.

  6. Caregivers’ hair cortisol: a possible biomarker of chronic stress is associated with obesity measures among children with disabilities

    OpenAIRE

    Chen, Xiaoli; Gelaye, Bizu; Velez, Juan Carlos; Barbosa,Clarita; Pepper, Micah; Andrade, Asterio; Gao, Wei; Kirschbaum, Clemens; Williams, Michelle A.

    2015-01-01

    Background: The stress of caring for a loved one with chronic illness has been associated with childhood obesity. Hair cortisol has been proposed as a novel biomarker of chronic psychological stress. This study aimed to evaluate the associations between caregivers’ chronic stress evaluated by hair cortisol concentrations (HCC) and obesity measures among children with disabilities such as autism. Methods: Eighty-five dyads of children with disabilities and their primary caregivers participated...

  7. A systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury. Results of the International Collaboration on MTBI Prognosis (ICoMP)

    DEFF Research Database (Denmark)

    Godbolt, Allison; Cancelliere, Carol; Hincapié, Cesar A

    2014-01-01

    -defined criteria. Peer-reviewed reports in six languages were considered. Study selection: Systematic reviews, meta-analyses, randomized controlled trials (RCTs), cohorts and case-control studies, with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of dementia or CCI after MTBI were selected...... synthesis: Evidence from accepted studies was synthesized qualitatively according to modified SIGN criteria and prognostic information was prioritized as exploratory or confirmatory, according to design. Of 77 914 records screened, 304 articles were eligible and reviewed. Methodological quality......Objective: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI), following mild traumatic brain injury (MTBI). Data sources: MEDLINE and other databases were searched (2001–2012), using a previously published search strategy and pre...

  8. 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.

  9. Metabolic characteristics and oxidative damage to skeletal muscle in broiler chickens exposed to chronic heat stress.

    Science.gov (United States)

    Azad, M A K; Kikusato, M; Maekawa, T; Shirakawa, H; Toyomizu, M

    2010-03-01

    Emerging evidence has shown that acute heat exposure affects metabolic characteristics and causes oxidative damage to skeletal muscle in birds. Little is known, however, about such phenomena under chronic heat stress conditions. To address this, we designed the present study to determine the influence of cyclic (32 to 24 to 32 degrees C: 32 degrees C for 8 h/d, 32-24-32HS ), and constant (32 and 34 degrees C, 32HS and 34HS, respectively) heat exposure on the metabolic and peroxide status in skeletal muscle of 4-wk-old male broiler chickens. Heat stress, particularly in the 32HS and 34HS groups, depressed feed intake and growth, while cyclic high temperature gave rise to a less severe stress response in performance terms. Malondialdehyde (MDA) levels in skeletal muscle were enhanced (Pstress model. The 3HADH (3-hydroxyacyl CoA dehydrogenase related to fatty acid oxidation) and CS (citrate synthase) enzyme activities were lowered (Pchickens. On exposure to chronic heat stress, GPx activity remained relatively constant, though a temperature-dependent elevation in Cu/Zn-SOD activity was observed, implying that anti-oxidation ability was disturbed by the chronic stress condition. From these results it can be concluded that chronic heat stress did not induce oxidative damage to a major extent. This may probably be due to a decrease in metabolic oxidation capacity or due to a self-propagating scavenging system, though the system was not fully activated.

  10. Behavioral effects of chronic stress in the Fmr1 mouse model for fragile X syndrome.

    Science.gov (United States)

    Lemaire-Mayo, Valerie; Subashi, Enejda; Henkous, Nadia; Beracochea, Daniel; Pietropaolo, Susanna

    2017-03-01

    Fragile X Syndrome (FXS) is a pervasive developmental disorder due to a mutation in the FMR1 X-linked gene. Despite its clear genetic cause, the expression of FXS symptoms is known to be modulated by environmental factors, including stress. Furthermore, several studies have shown disturbances in stress regulatory systems in FXS patients and Fmr1 mice. These studies have mostly focused on the hormonal responses to stress, using the acute exposure to a single type of stressor. Hence, little is known about the behavioral effects of stress in FXS, and the importance of the nature of the stressing procedure, especially in the context of a repeated exposure that more closely resembles real life conditions. Here we evaluated the effects of chronic exposure to different types of stress (i.e., either repeated restraint or unpredictable stress) on the behavioral phenotype of adult Fmr1 mice. Our results demonstrated that chronic stress induced deficits in social interaction and working memory only in WT mice and the impact of stress depended on the type of stressors and the specific behavior tested. Our data suggest that the behavioral sensitivity to stress is dramatically reduced in FXS, opening new views on the impact of gene-environment interactions in this pathology.

  11. Chronic environmental stress enhances tolerance to seasonal gradual warming in marine mussels

    Science.gov (United States)

    Múgica, Maria; Izagirre, Urtzi; Sokolova, Inna M.

    2017-01-01

    In global climate change scenarios, seawater warming acts in concert with multiple stress sources, which may enhance the susceptibility of marine biota to thermal stress. Here, the responsiveness to seasonal gradual warming was investigated in temperate mussels from a chronically stressed population in comparison with a healthy one. Stressed and healthy mussels were subjected to gradual temperature elevation for 8 days (1°C per day; fall: 16–24°C, winter: 12–20°C, summer: 20–28°C) and kept at elevated temperature for 3 weeks. Healthy mussels experienced thermal stress and entered the time-limited survival period in the fall, became acclimated in winter and exhibited sublethal damage in summer. In stressed mussels, thermal stress and subsequent health deterioration were elicited in the fall but no transition into the critical period of time-limited survival was observed. Stressed mussels did not become acclimated to 20°C in winter, when they experienced low-to-moderate thermal stress, and did not experience sublethal damage at 28°C in summer, showing instead signs of metabolic rate depression. Overall, although the thermal threshold was lowered in chronically stressed mussels, they exhibited enhanced tolerance to seasonal gradual warming, especially in summer. These results challenge current assumptions on the susceptibility of marine biota to the interactive effects of seawater warming and pollution. PMID:28333994

  12. Chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring of the striatum.

    Science.gov (United States)

    Taylor, S B; Anglin, J M; Paode, P R; Riggert, A G; Olive, M F; Conrad, C D

    2014-11-07

    Chronic stress is an established risk factor in the development of addiction. Addiction is characterized by a progressive transition from casual drug use to habitual and compulsive drug use. The ability of chronic stress to facilitate the transition to addiction may be mediated by increased engagement of the neurocircuitries underlying habitual behavior and addiction. In the present study, striatal morphology was evaluated after 2 weeks of chronic variable stress in male Sprague-Dawley rats. Dendritic complexity of medium spiny neurons was visualized and quantified with Golgi staining in the dorsolateral and dorsomedial striatum, as well as in the nucleus accumbens core and shell. In separate cohorts, the effects of chronic stress on habitual behavior and the acute locomotor response to methamphetamine were also assessed. Chronic stress resulted in increased dendritic complexity in the dorsolateral striatum and nucleus accumbens core, regions implicated in habitual behavior and addiction, while decreased complexity was found in the nucleus accumbens shell, a region critical for the initial rewarding effects of drugs of abuse. Chronic stress did not affect dendritic complexity in the dorsomedial striatum. A parallel shift toward habitual learning strategies following chronic stress was also identified. There was an initial reduction in acute locomotor response to methamphetamine, but no lasting effect as a result of chronic stress exposure. These findings suggest that chronic stress may facilitate the recruitment of habit- and addiction-related neurocircuitries through neuronal restructuring in the striatum.

  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. Chronic psychological stress suppresses contact hypersensitivity: potential roles of dysregulated cell trafficking and decreased IFN-γ production.

    Science.gov (United States)

    Hall, Jessica M F; Witter, Alexandra R; Racine, Ronny R; Berg, Rance E; Podawiltz, Alan; Jones, Harlan; Mummert, Mark E

    2014-02-01

    Increasing evidence shows that psychological stress can have dramatic impacts on the immune system, particularly the cutaneous immune response in dermatological disorders. While there have been many studies examining the impact of acute psychological stress on contact hypersensitivity there are relatively few studies concerning the impact of chronic psychological stress. Furthermore, the local immunological mechanisms by which chronic psychological stress impacts contact hypersensitivity still remain to be explored. Here we show that restraint-induced chronic psychological stress stimulates activation of the hypothalamus-pituitary-adrenal axis and delays weight gain in female BALB/c mice. We observed that chronic psychological stress reduces the cutaneous immune response as evidence by reduced ear swelling. This correlated with a significant decrease in the inflammatory cell infiltrate. On the other hand, chronic psychological stress does not influence T cell proliferation, activation, or sensitivity to corticosterone but does increase CD4(+) and CD8(+) T cell percentages in draining lymph nodes during a contact hypersensitivity reaction. Chronic psychological stress induces a decrease in overall circulating white blood cells, lymphocytes, and monocytes during a contact hypersensitivity reaction suggesting extravasation from the circulation. Finally, we found markedly reduced local IFN-γ production in chronically stressed animals. Based on these findings we propose that chronic psychological stress reduces contact hypersensitivity due to dysregulated cell trafficking and reduced production of IFN-γ.

  16. Effects of chronic stress on the auditory system and fear learning: an evolutionary approach.

    Science.gov (United States)

    Dagnino-Subiabre, Alexies

    2013-01-01

    Stress is a complex biological reaction common to all living organisms that allows them to adapt to their environments. Chronic stress alters the dendritic architecture and function of the limbic brain areas that affect memory, learning, and emotional processing. This review summarizes our research about chronic stress effects on the auditory system, providing the details of how we developed the main hypotheses that currently guide our research. The aims of our studies are to (1) determine how chronic stress impairs the dendritic morphology of the main nuclei of the rat auditory system, the inferior colliculus (auditory mesencephalon), the medial geniculate nucleus (auditory thalamus), and the primary auditory cortex; (2) correlate the anatomic alterations with the impairments of auditory fear learning; and (3) investigate how the stress-induced alterations in the rat limbic system may spread to nonlimbic areas, affecting specific sensory system, such as the auditory and olfactory systems, and complex cognitive functions, such as auditory attention. Finally, this article gives a new evolutionary approach to understanding the neurobiology of stress and the stress-related disorders.

  17. 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.

  18. Influence of hypothalamic IL-6/gp130 receptor signaling on the HPA axis response to chronic stress.

    Science.gov (United States)

    Girotti, Milena; Donegan, Jennifer J; Morilak, David A

    2013-07-01

    Abnormal basal activity and stress-evoked reactivity of the hypothalamic-pituitary-adrenal (HPA) axis are often seen in depression, implicating HPA axis dysfunction as a potentially causative or exacerbating factor. Chronic stress is also a factor in depression, but it is not known what may underlie the shift from adaptive to maladaptive HPA activity over the course of chronic stress. Interleukin 6 (IL-6), a stress-inducible cytokine that signals through gp130 and IL-6Rα receptors to activate the JAK/STAT3 signaling cascade, is elevated in some subtypes of depression, and may have a modulatory effect on HPA activation, raising the possibility that IL-6 contributes to depression through effects on the HPA axis. In this study, we examined the effects of three different stress modalities, acute footshock, chronic intermittent cold (CIC) stress and chronic unpredictable stress (CUS) on IL-6 signaling in the hypothalamus. We also investigated whether IL-6 modulates the HPA response to chronic stress, by blocking IL-6 signaling in the brain during CIC stress using either a neutralizing antibody or an inhibitor of STAT3 phosphorylation. We show that IL-6 and STAT3 in the hypothalamus are activated in response to footshock and CUS. We also found that basal IL-6 signaling through the JAK/STAT3 pathway is required for the sustained CORT response to chronic, but not acute, cold stress and therefore is a potential determinant of plasticity in the HPA axis specifically during chronic stress exposure.

  19. 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.

  20. Chronic stress induces adrenal hyperplasia and hypertrophy in a subregion-specific manner.

    Science.gov (United States)

    Ulrich-Lai, Yvonne M; Figueiredo, Helmer F; Ostrander, Michelle M; Choi, Dennis C; Engeland, William C; Herman, James P

    2006-11-01

    The adrenal gland is an essential stress-responsive organ that is part of both the hypothalamic-pituitary-adrenal axis and the sympatho-adrenomedullary system. Chronic stress exposure commonly increases adrenal weight, but it is not known to what extent this growth is due to cellular hyperplasia or hypertrophy and whether it is subregion specific. Moreover, it is not clear whether increased production of adrenal glucocorticoid after chronic stress is due to increased sensitivity to adrenocorticotropic hormone (ACTH) vs. increased maximal output. The present studies use a 14-day chronic variable stress (CVS) paradigm in adult male rats to assess the effects of chronic stress on adrenal growth and corticosterone steroidogenesis. Exogenous ACTH administration (0-895 ng/100 g body wt) to dexamethasone-blocked rats demonstrated that CVS increased maximal plasma and adrenal corticosterone responses to ACTH without affecting sensitivity. This enhanced function was associated with increased adrenal weight, DNA and RNA content, and RNA/DNA ratio after CVS, suggesting that both cellular hyperplasia and hypertrophy occurred. Unbiased stereological counting of cells labeled for Ki67 (cell division marker) or 4,6-diamidino-2-phenylindole (nuclear marker), combined with zone specific markers, showed that CVS induced hyperplasia in the outer zona fasciculata, hypertrophy in the inner zona fasciculata and medulla, and reduced cell size in the zona glomerulosa. Collectively, these results demonstrate that increased adrenal weight after CVS is due to hyperplasia and hypertrophy that occur in specific adrenal subregions and is associated with increased maximal corticosterone responses to ACTH. These chronic stress-induced changes in adrenal growth and function may have implications for patients with stress-related disorders.

  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 stress impairs learning and hippocampal cell proliferation in senescence-accelerated prone mice.

    Science.gov (United States)

    Yan, Weihong; Zhang, Ting; Jia, Weiping; Sun, Xiaojiang; Liu, Xueyuan

    2011-02-25

    Chronic stress can induce cognitive impairment. It is unclear whether a higher susceptibility to chronic stress is associated with the progression of pathological brain aging. Senescence-accelerated prone mouse 8 (SAMP8) is a naturally occurring animal model of accelerated brain aging. Senescence-accelerated resistant mouse 1 (SAMR1) is usually used as the normal control. In this study, we examined the effects of chronic restraint stress (CRS) on learning in the Y-maze, hippocampal cell proliferation, and the expression of brain-derived neurotrophic factor (BDNF) in the hippocampus of 4-month-old SAMP8 and SAMR1. The results showed that exposure to CRS impaired learning and hippocampal cell proliferation in SAMP8 and SAMR1 but to a much greater extent in SAMP8. Furthermore, CRS significantly decreased the expression of BDNF protein and mRNA in the hippocampus of SAMP8 and SAMR1. These data indicated that SAMP8 is more sensitive to the deleterious effects of CRS on learning than SAMR1. A greater decrease in hippocampal cell proliferation caused by chronic stress may be part of the underlying mechanism for the more severe learning deficit observed in SAMP8. In addition, our findings suggested a role of BDNF in the stress-induced impairment of learning and hippocampal cell proliferation in both strains.

  3. 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.

  4. Effects of (-)-Sesamin on Chronic Stress-Induced Anxiety Disorders in Mice.

    Science.gov (United States)

    Zhao, Ting Ting; Shin, Keon Sung; Park, Hyun Jin; Yi, Bo Ram; Lee, Kyung Eun; Lee, Myung Koo

    2016-12-19

    This study investigated the effects of (-)-sesamin on chronic electric footshock (EF) stress-induced anxiety disorders in mice. Mice were treated with (-)-sesamin (25 and 50 mg/kg) orally once a day for 21 days prior to exposure to EF stress (0.6 mA, 1 s every 5 s, 3 min). Mice treated with (-)-sesamin (25 and 50 mg/kg) exhibited less severe decreases in the number of open arm entries and time spent on open arms in the elevated plus-maze test and the distance traveled in the open field test following exposure to chronic EF stress. Similarly, mice treated with (-)-sesamin exhibited significantly less severe decreases in brain levels of dopamine, norepinephrine, and serotonin following exposure to chronic EF stress. Increases in serum levels of corticosterone and expression of c-Fos were also less pronounced in mice treated with (-)-sesamin (25 and 50 mg/kg). These results suggest that (-)-sesamin may protect against the effects of chronic EF stress-induced anxiety disorders by modulating dopamine, norepinephrine, and serotonin levels, c-Fos expression, and corticosterone levels.

  5. 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

    2015-01-01

    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

  6. 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

  7. Identification of Risk Factors for Chronic Posttraumatic Stress Disorder (PTSD)

    Science.gov (United States)

    2009-06-01

    Miller, Wolf, Martin , Kaloupek, & Keane, 2008). Furthermore, PTSD hyperarousal symptoms have been linked to greater aggressive tendencies among male...dimensional conceptualization of posttraumatic stress reactions on the basis of taxometric procedures (e.g. Forbes, Haslam, Williams, & Creamer , 2005) and...New York State Psychiatric Institute, Biometrics Research. Forbes, D., Haslam, N., Williams, B. J., & Creamer , M. (2005). Testing the latent

  8. Molecular Indicators of Chronic Stress in a Model Pinniped - The Northern Elephant Seal

    Science.gov (United States)

    2015-09-30

    experienced recent acute stress, and chronically stressed animals can offer substantial information relevant to management and conservation of marine...Overview of Experimental Design The proposed work will be conducted in northern elephant seals (Mirounga angustirostris), a tractable marine mammal system...fall. This life- history stage represents a baseline state in this species with no additional confounding features such as breeding or molting. In

  9. Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress.

    Science.gov (United States)

    Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula; Eagle, Andrew; Mazei-Robison, Michelle; Nestler, Eric J; Robison, A J

    2015-12-01

    Major depressive disorder is thought to arise in part from dysfunction of the brain's "reward circuitry", consisting of the mesolimbic dopamine system and the glutamatergic and neuromodulatory inputs onto this system. Both chronic stress and antidepressant treatment regulate gene transcription in many of the brain regions that make up these circuits, but the exact nature of the transcription factors and target genes involved in these processes remain unclear. Here, we demonstrate induction of the FosB family of transcription factors in ∼25 distinct regions of adult mouse brain, including many parts of the reward circuitry, by chronic exposure to the antidepressant fluoxetine. We further uncover specific patterns of FosB gene product expression (i.e., differential expression of full-length FosB, ΔFosB, and Δ2ΔFosB) in brain regions associated with depression--the nucleus accumbens (NAc), prefrontal cortex (PFC), and hippocampus--in response to chronic fluoxetine treatment, and contrast these patterns with differential induction of FosB isoforms in the chronic social defeat stress model of depression with and without fluoxetine treatment. We find that chronic fluoxetine, in contrast to stress, causes induction of the unstable full-length FosB isoform in the NAc, PFC, and hippocampus even 24 h following the final injection, indicating that these brain regions may undergo chronic activation when fluoxetine is on board, even in the absence of stress. We also find that only the stable ΔFosB isoform correlates with behavioral responses to stress. These data suggest that NAc, PFC, and hippocampus may present useful targets for directed intervention in mood disorders (ie, brain stimulation or gene therapy), and that determining the gene targets of FosB-mediated transcription in these brain regions in response to fluoxetine may yield novel inroads for pharmaceutical intervention in depressive disorders.

  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. Effects of oxytocin on behaviour and memory in rats subjected to chronic restrained stress.

    Science.gov (United States)

    Kunchulia, M; Bolkvadze, T; Zhvania, M; Kotaria, N; Kiladze, M

    2010-10-01

    We studied whether 21 days of restraint chronic stress would affect the contextual fear conditioning, a memory task with hippocampal-dependent components and anxiety- like behavior in the open field, and to determine whether oxytocin treatment could prevent the chronic stress induced memory and emotional disturbances. Restraint-stressed rats were injected daily (21 days) with oxytocin (1 mg/kg) or saline then tested in open field (day 22) and contextual fear conditioning task (days 23-24). Our data demonstrate that chronic restraint stress induces some behavioural changes in both saline-treated and oxytocin-treated animals. Particularly, in the open field the animals both groups were characterized by hyper-locomotion. However, oxytocin-treated animals spent more time in the inner area of the open field, which indicates to decreased anxiety- related behaviour in oxytocin-treated animals versus the saline-treated ones. In additional restraint stress decreased freezing reaction to context, irrespective of whether oxytocin was given or not. Our findings indicate that during stress OT may be involved in the regulation of emotional behavior and memory via different ways. The elucidation of corresponding mechanisms is of great importance.

  12. Gonadal hormones differently modulate cutaneous wound healing of chronically stressed mice.

    Science.gov (United States)

    Romana-Souza, Bruna; Assis de Brito, Thatiana L; Pereira, Gabriela R; Monte-Alto-Costa, Andréa

    2014-02-01

    Gonadal hormones influence physiological responses to stress and cutaneous wound healing. The aim of this study was to investigate the role of gonadal hormones on cutaneous wound healing in chronically stressed mice. Male and female mice were gonadectomized, and after 25 days, they were spun daily at 115 rpm for 15 min every hour until euthanasia. Twenty-eight days after the gonadectomy, an excisional lesion was created. The animals were killed 7 or 14 days after wounding, and the lesions were collected. Myofibroblast density, macrophage number, catecholamine level, collagen deposition, and blood vessel number were evaluated. In the intact and gonadectomized groups, stress increased the plasma catecholamine levels in both genders. In intact groups, stress impaired wound contraction and re-epithelialization and increased the macrophage number in males but not in females. In addition, stress compromised myofibroblastic differentiation and blood vessel formation and decreased collagen deposition in males but not in females. In contrast to intact mice, wound healing in ovariectomized female mice was affected by stress, while wound healing in castrated male mice was not. In conclusion, gender differences contribute to the cutaneous wound healing of chronically stressed mice. In addition, androgens contribute to the stress-induced impairment of the healing of cutaneous wounds but estrogens inhibit it.

  13. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

    Directory of Open Access Journals (Sweden)

    Radouil Tzekov

    Full Text Available Repetitive mild traumatic brain injury (r-mTBI results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL, tubulin (TUBB2A, TUBA4A, microtubule-associated proteins (MAP1A, MAP1B, collagen (COL6A1, COL6A3 and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1, APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC, including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the

  14. Sub-Chronic Neuropathological and Biochemical Changes in Mouse Visual System after Repetitive Mild Traumatic Brain Injury.

    Science.gov (United States)

    Tzekov, Radouil; Dawson, Clint; Orlando, Megan; Mouzon, Benoit; Reed, Jon; Evans, James; Crynen, Gogce; Mullan, Michael; Crawford, Fiona

    2016-01-01

    Repetitive mild traumatic brain injury (r-mTBI) results in neuropathological and biochemical consequences in the human visual system. Using a recently developed mouse model of r-mTBI, with control mice receiving repetitive anesthesia alone (r-sham) we assessed the effects on the retina and optic nerve using histology, immunohistochemistry, proteomic and lipidomic analyses at 3 weeks post injury. Retina tissue was used to determine retinal ganglion cell (RGC) number, while optic nerve tissue was examined for cellularity, myelin content, protein and lipid changes. Increased cellularity and areas of demyelination were clearly detectable in optic nerves in r-mTBI, but not in r-sham. These changes were accompanied by a ~25% decrease in the total number of Brn3a-positive RGCs. Proteomic analysis of the optic nerves demonstrated various changes consistent with a negative effect of r-mTBI on major cellular processes like depolymerization of microtubules, disassembly of filaments and loss of neurons, manifested by decrease of several proteins, including neurofilaments (NEFH, NEFM, NEFL), tubulin (TUBB2A, TUBA4A), microtubule-associated proteins (MAP1A, MAP1B), collagen (COL6A1, COL6A3) and increased expression of other proteins, including heat shock proteins (HSP90B1, HSPB1), APOE and cathepsin D. Lipidomic analysis showed quantitative changes in a number of phospholipid species, including a significant increase in the total amount of lysophosphatidylcholine (LPC), including the molecular species 16:0, a known demyelinating agent. The overall amount of some ether phospholipids, like ether LPC, ether phosphatidylcholine and ether lysophosphatidylethanolamine were also increased, while the majority of individual molecular species of ester phospholipids, like phosphatidylcholine and phosphatidylethanolamine, were decreased. Results from the biochemical analysis correlate well with changes detected by histological and immunohistochemical methods and indicate the involvement of

  15. Effects of ethanol on social avoidance induced by chronic social defeat stress in mice.

    Science.gov (United States)

    Favoretto, Cristiane A; Macedo, Giovana C; Quadros, Isabel M H

    2017-01-01

    In rodents, chronic social defeat stress promotes deficits in social interest and social interaction. We further explored these antisocial effects by comparing the consequences of two different defeat stress protocols (episodic vs. continuous stress) in a social investigation test. We expected that continuous, but not episodic, stress would induce social deficits in this model. Furthermore, we tested whether a potentially anxiolytic dose of ethanol reverses social deficits induced by defeat stress. Male Swiss mice were exposed to a 10-day social defeat protocol, using daily confrontations with an aggressive resident mouse. Episodic stress consisted of brief defeat episodes, after which the defeated mouse was returned to its home cage, until the next defeat 24 h later (n = 7-11/group). For continuous stress, similar defeat episodes were followed by cohabitation with the aggressive resident for 24 h, separated by a perforated divider, until the following defeat (n = 8-14/group). Eight days after stress termination, defeated and control mice were assessed in a social investigation test, after treatment with ethanol (1.0 g/kg, i.p.) or 0.9% saline. Considering the time spent investigating a social target, mice exposed to episodic or continuous social stress showed less social investigation than controls (p stress or ethanol. Thus, a history of social defeat stress, whether episodic or continuous, promotes deficits in social investigation that were not reversed by acute treatment with ethanol.

  16. Acute heat stress impairs performance parameters and induces mild intestinal enteritis in broiler chickens: role of acute hypothalamic-pituitary-adrenal axis activation.

    Science.gov (United States)

    Quinteiro-Filho, W M; Rodrigues, M V; Ribeiro, A; Ferraz-de-Paula, V; Pinheiro, M L; Sá, L R M; Ferreira, A J P; Palermo-Neto, J

    2012-06-01

    Studies on the environmental consequences of stress are relevant for economic and animal welfare reasons. We recently reported that long-term heat stressors (31 ± 1°C and 36 ± 1°C for 10 h/d) applied to broiler chickens (Gallus gallus domesticus) from d 35 to 42 of life increased serum corticosterone concentrations, decreased performance variables and the macrophage oxidative burst, and produced mild, multifocal acute enteritis. Being cognizant of the relevance of acute heat stress on tropical and subtropical poultry production, we designed the current experiment to analyze, from a neuroimmune perspective, the effects of an acute heat stress (31 ± 1°C for 10 h on d 35 of life) on serum corticosterone, performance variables, intestinal histology, and peritoneal macrophage activity in chickens. We demonstrated that the acute heat stress increased serum corticosterone concentrations and mortality and decreased food intake, BW gain, and feed conversion (P 0.05). Increases in the basal and the Staphylococcus aureus-induced macrophage oxidative bursts and a decrease in the percentage of macrophages performing phagocytosis were also observed. Finally, mild, multifocal acute enteritis, characterized by the increased presence of lymphocytes and plasmocytes within the lamina propria of the jejunum, was also observed. We found that the stress-induced hypothalamic-pituitary-adrenal axis activation was responsible for the negative effects observed on chicken performance and immune function as well as for the changes in the intestinal mucosa. The data presented here corroborate with those presented in other studies in the field of neuroimmunomodulation and open new avenues for the improvement of broiler chicken welfare and production performance.

  17. 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…

  18. 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.

  19. 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

  20. 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...

  1. Chronic psychosocial stress makes rats more 'pessimistic' in the ambiguous-cue interpretation paradigm.

    Science.gov (United States)

    Papciak, Justyna; Popik, Piotr; Fuchs, Eberhard; Rygula, Rafal

    2013-11-01

    Human decisions are often biased by emotions. Stressed and depressed individuals tend to make negative, pessimistic judgements while those in positive affective states are often more optimistic. Chronic psychosocial stress has previously been shown to induce a spectrum of behavioural and physiological changes in rats that are considered the correlates of depressive symptoms in humans. In this study, we investigate whether chronic social defeat makes animals more 'pessimistic'. To measure the changes in cognitive judgement bias, we applied the ambiguous-cue interpretation paradigm. In the operant boxes, the rats were trained to press one lever in response to one tone to receive a reward and to press another lever in response to a different tone to avoid punishment. Cognitive bias was tested by measuring the pattern of animals' responses to a tone of intermediate frequency (ambiguous-cue). To induce chronic psychosocial stress, we subjected the animals to daily social defeat in the resident-intruder paradigm for 3 weeks. We report that chronic psychosocial stress makes rats more pessimistic.

  2. Homeostatic maintenance in excitability of tree shrew hippocampal CA3 pyramidal neurons after chronic stress

    NARCIS (Netherlands)

    Kole, MHP; Czeh, B; Fuchs, E

    2004-01-01

    The experience of chronic stress induces a reversible regression of hippocampal CA3 apical neuron dendrites. Although such postsynaptic membrane reduction will obviously diminish the possibility of synaptic input, the consequences for the functional membrane properties of these cells are not well un

  3. Brain opioid receptor density relates to stereotypies in chronically stressed pigs

    NARCIS (Netherlands)

    Loijens, L.W.S.; Schouten, W.G.P.; Wiepkema, P.R.; Wiegant, V.M.

    1999-01-01

    Opioid receptor densities were measured in the hippocampus of chronically stressed (tethered) pigs to study the involvement of endogenous opioid systems in stereotypy performance. Three groups of animals were housed tethered for 2 (n = 12), 5.5 (n = 12) and 8-9 months (n = 8), respectively, and the

  4. Correlates of cortisol in human hair: implications for epidemiologic studies on health effects of chronic stress.

    Science.gov (United States)

    Wosu, Adaeze C; Valdimarsdóttir, Unnur; Shields, Alexandra E; Williams, David R; Williams, Michelle A

    2013-12-01

    Assessment of cortisol concentrations in hair is one of the latest innovations for measuring long-term cortisol exposure. We performed a systematic review of correlates of cortisol in human hair to inform the design, analysis, and interpretation of future epidemiologic studies. Relevant publications were identified through electronic searches on PubMed, WorldCat, and Web of Science using keywords, "cortisol," "hair," "confounders," "chronic," "stress," and "correlates." Thirty-nine studies were included in this review. Notwithstanding scarce data and some inconsistencies, investigators have found hair cortisol concentrations to be associated with stress-related psychiatric symptoms and disorders (e.g., post-traumatic stress disorder), medical conditions indicating chronic activation of the hypothalamic-pituitary-adrenal axis (e.g., Cushing's syndrome), and other life situations associated with elevated risk of chronic stress (e.g., shiftwork). Results from some studies suggest that physical activity, adiposity, and substance abuse may be correlates of hair cortisol concentrations. In contrast to measures of short-term cortisol release (saliva, blood, and urine), cigarette smoking and use of oral contraceptives appear not to be associated with hair cortisol concentrations. Studies of pregnant women indicate increased hair cortisol concentrations across successive trimesters. The study of hair cortisol presents a unique opportunity to assess chronic alterations in cortisol concentrations in epidemiologic studies.

  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. Vortioxetine restores reversal learning impaired by 5-HT depletion or chronic intermittent cold stress in rats.

    Science.gov (United States)

    Wallace, Ashley; Pehrson, Alan L; Sánchez, Connie; Morilak, David A

    2014-10-01

    Current treatments for depression, including serotonin-specific reuptake inhibitors (SSRIs), are only partially effective, with a high incidence of residual symptoms, relapse, and treatment resistance. Loss of cognitive flexibility, a component of depression, is associated with dysregulation of the prefrontal cortex. Reversal learning, a form of cognitive flexibility, is impaired by chronic stress, a risk factor for depression, and the stress-induced impairment in reversal learning is sensitive to chronic SSRI treatment, and is mimicked by serotonin (5-HT) depletion. Vortioxetine, a novel, multimodal-acting antidepressant, is a 5-HT3, 5-HT7 and 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and inhibits the 5-HT transporter. Using adult male rats, we first investigated the direct effects of vortioxetine, acting at post-synaptic 5-HT receptors, on reversal learning that was compromised by 5-HT depletion using 4-chloro-DL-phenylalanine methyl ester hydrochloride (PCPA), effectively eliminating any contribution of 5-HT reuptake blockade. PCPA induced a reversal learning impairment that was alleviated by acute or sub-chronic vortioxetine administration, suggesting that post-synaptic 5-HT receptor activation contributes to the effects of vortioxetine. We then investigated the effects of chronic dietary administration of vortioxetine on reversal learning that had been compromised in intact animals exposed to chronic intermittent cold (CIC) stress, to assess vortioxetine's total pharmacological effect. CIC stress impaired reversal learning, and chronic vortioxetine administration prevented the reversal-learning deficit. Together, these results suggest that the direct effect of vortioxetine at 5-HT receptors may contribute to positive effects on cognitive flexibility deficits, and may enhance the effect of 5-HT reuptake blockade.

  7. Expression dynamics of HSP70 during chronic heat stress in Tharparkar cattle

    Science.gov (United States)

    Bharati, Jaya; Dangi, S. S.; Chouhan, V. S.; Mishra, S. R.; Bharti, M. K.; Verma, V.; Shankar, O.; Yadav, V. P.; Das, K.; Paul, A.; Bag, S.; Maurya, V. P.; Singh, G.; Kumar, P.; Sarkar, M.

    2016-12-01

    Six male Tharparkar cattle aged 2-3 years were selected for the study. The animals were acclimatized in the psychrometric chamber at thermoneutral zone (TNZ) for 15 days and then exposed to 42 °C temperature up to 23 days followed by 12 days of recovery period. Physiological responses were estimated, and peripheral blood mononuclear cells (PBMCs) were isolated at TNZ on day 1, day 5, and day 12; after 6 h of heat stress exposure on day 16 to day 20, day 25, day 30, day 32, day 34, day 36, and day 38; and a recovery period on day 45 and day 50. The PBMCs were cultured to study the effect of thermal challenge on HSP70 messenger RNA (mRNA) expression pattern at different temperature-time combinations. The mRNA and protein expression of HSP70 in PBMCs along with serum extracellular HSP70 (eHSP70) was increased (P heat stress challenge treatment as compared to control in cultured PBMCs. HSP70 expression was found to be higher (P heat exposure (corresponds to chronic heat stress) as compared to the first 5 days of heat stress (corresponds to short-term heat stress) and control period at TNZ. The present findings indicate that HSP70 is possibly involved in heat stress adaptive response in Tharparkar cattle and the biphasic expression pattern may be providing a second window of protection during chronic heat stress.

  8. Chronic stress during adolescence impairs and improves learning and memory in adulthood

    Directory of Open Access Journals (Sweden)

    Lauren Evelyn Chaby

    2015-12-01

    Full Text Available Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they age is not well understood. We determined how chronic unpredictable stress during adolescence affects multiple learning and memory processes in adulthood. Using male Sprague Dawley rats, we measured learning (both associative and reversal and memory (both reference and working starting 110 days after completion of the adolescent-stress treatment. We found that adolescent stress affected adult cognitive abilities in a context-dependent way. Compared to rats reared without stress, adolescent-stressed rats exhibited enhanced reversal learning, an indicator of behavioral flexibility, but showed no change in associative learning and reference memory abilities. Working memory, which in humans is thought to underpin reasoning, mathematical skills, and reading comprehension, may be enhanced by exposure to adolescent stress. However, when adolescent-stressed animals were tested after a novel disturbance, they exhibited a 5-fold decrease in working memory performance while unstressed rats continued to exhibit a linear learning curve. These results emphasize the capacity for stress during adolescence to transform the cognitive abilities of adult animals, even after stress exposure has ceased and animals have resided in safe environments for the majority of their lifespans.

  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. Chronic shin splints. Classification and management of medial tibial stress syndrome.

    Science.gov (United States)

    Detmer, D E

    1986-01-01

    A clinical classification and treatment programme has been developed for chronic medial tibial stress syndrome. Medial tibial stress syndrome has been reported to be either tibial stress fracture or microfracture, tibial periostitis, or distal deep posterior chronic compartment syndrome. Three chronic types exist and may coexist: Type I (tibial microfracture, bone stress reaction or cortical fracture); type II (periostalgia from chronic avulsion of the periosteum at the periosteal-fascial junction); and type III (chronic compartment syndrome syndrome). Type I disease is treated nonoperatively. Operations for resistant types II and III medial tibial stress syndrome were performed in 41 patients. Bilaterality was common (type II, 50% type III, 88%). Seven had coexistent type II/III; one had type I/II. Preoperative symptoms averaged 24 months in type II, 6 months in type III, and 33 months in types II/III. Mean age was 22 years (15 to 51). Resting compartment pressures were normal in type II (mean 12 mm Hg) and elevated in type III and type II/III (mean 23 mm Hg). Type II and type II/III patients received fasciotomy plus periosteal cauterisation. Type III patients had fasciotomy only. All procedures were performed on an outpatient basis using local anaesthesia. Follow up was complete and averaged 6 months (2 to 14 months). Improved performance was as follows: type II, 93%, type III, 100%; type II/III, 86%. Complete cures were as follows: type II, 78%; type III, 75%; and type II/III, 57%. This experience suggests that with precise diagnosis and treatment involving minimal risk and cost the athlete has a reasonable chance of return to full activity.

  11. Using Complementary and Alternative Medicine (CAM) to Promote Stress Resilience in Those with Co-Occurring Mild TBI and PTSD

    Science.gov (United States)

    2015-04-01

    affects aspects of day-to-day function, such as memory , sleep, mood, psychiatric health and stress resilience. This information will help identify...health, memory and in a laboratory stress task. Veterans have been recruited since regulatory approval was obtained (August 2012) and enrolled in the...1 Award Number: W81XWH-12-1-0037 TITLE: : Using Complementary and Alternative Medicine (CAM) to Promote Stress Resilience in those with Co

  12. Safety and tolerability of the novel non-steroidal mineralocorticoid receptor antagonist BAY 94-8862 in patients with chronic heart failure and mild or moderate chronic kidney disease

    DEFF Research Database (Denmark)

    Pitt, Bertram; Kober, Lars; Ponikowski, Piotr;

    2013-01-01

    Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non-steroida......Mineralocorticoid receptor antagonists (MRAs) improve outcomes in patients with heart failure and reduced left ventricular ejection fraction (HFrEF), but their use is limited by hyperkalaemia and/or worsening renal function (WRF). BAY 94-8862 is a highly selective and strongly potent non......-steroidal MRA. We investigated its safety and tolerability in patients with HFrEF associated with mild or moderate chronic kidney disease (CKD)....

  13. Obesity, diabetes mellitus, atherosclerosis and chronic periodontitis: a shared pathology via oxidative stress and mitochondrial dysfunction?

    Science.gov (United States)

    Bullon, Pedro; Newman, Hubert N; Battino, Maurizio

    2014-02-01

    As many diseases have been shown to have several or indirect causes (i.e. are multifactorial) the question is what is the relative importance of each factor in a given disease? Also, what happens when some diseases, although apparently disparate, share causative factors and/or tissue pathologies? Host inflammation response mechanisms are largely shared by the body's different tissues and systems and only recently has special attention been paid to the possible linkages among chronic periodontitis and other chronic systemic diseases. The aim of this review was to consider and discuss the mounting evidence that the basis for the inter-relationships between chronic periodontitis and atheromatous disease and diabetes lie at a fundamental intracellular level, namely oxidative stress and mitochondrial dysfunction, as a meeting background among such chronic diseases and periodontitis.

  14. Chronic Stress During Adolescence Impairs and Improves Learning and Memory in Adulthood.

    Science.gov (United States)

    Chaby, Lauren E; Cavigelli, Sonia A; Hirrlinger, Amy M; Lim, James; Warg, Kendall M; Braithwaite, Victoria A

    2015-01-01

    HIGHLIGHTS This study tested the effects of adolescent-stress on adult learning and memory.Adolescent-stressed rats had enhanced reversal learning compared to unstressed rats.Adolescent-stress exposure made working memory more vulnerable to disturbance.Adolescent-stress did not affect adult associative learning or reference memory. Exposure to acute stress can cause a myriad of cognitive impairments, but whether negative experiences continue to hinder individual as they age is not as well understood. We determined how chronic unpredictable stress during adolescence affects multiple learning and memory processes in adulthood. Using male Sprague Dawley rats, we measured learning (both associative and reversal) and memory (both reference and working) starting 110 days after completion of an adolescent-stress treatment. We found that adolescent-stress affected adult cognitive abilities in a context-dependent way. Compared to rats reared without stress, adolescent-stressed rats exhibited enhanced reversal learning, an indicator of behavioral flexibility, but showed no change in associative learning and reference memory abilities. Working memory, which in humans is thought to underpin reasoning, mathematical skills, and reading comprehension, may be enhanced by exposure to adolescent-stress. However, when adolescent-stressed animals were tested after a novel disturbance, they exhibited a 5-fold decrease in working memory performance while unstressed rats continued to exhibit a linear learning curve. These results emphasize the capacity for stress during adolescence to transform the cognitive abilities of adult animals, even after stress exposure has ceased and animals have resided in safe environments for the majority of their lifespans.

  15. Response of Mouse Zygotes Treated with Mild Hydrogen Peroxide as a Model to Reveal Novel Mechanisms of Oxidative Stress-Induced Injury in Early Embryos

    Science.gov (United States)

    2016-01-01

    Our study aimed to develop embryo models to evaluate the impact of oxidative stress on embryo development. Mouse zygotes, which stayed at G1 phase, were treated with prepared culture medium (containing 0.00, 0.01, 0.02, 0.03, 0.04, 0.05, or 0.1 mM hydrogen peroxide (H2O2)) for 30 min in experiment 1. The dose-effects of H2O2 on embryo development were investigated via comparisons of the formation rate at each stage (2- and 4-cell embryos and blastocysts). Experiment 2 was carried out to compare behaviors of embryos in a mild oxidative-stressed status (0.03 mM H2O2) with those in a control (0 mM H2O2). Reactive oxygen species (ROS) levels, variation of mitochondrial membrane potential (MMP), expression of γH2AX, and cell apoptosis rate of blastocyst were detected. We observed a dose-dependent decrease on cleavage and blastocyst rates. Besides, higher level of ROS, rapid reduction of MMP, and the appearance of γH2AX revealed that embryos are injured early in mild oxidative stress. Additionally, γH2AX may involve during DNA damage response in early embryos. And the apoptotic rate of blastocyst may significantly increase when DNA damage repair is inadequate. Most importantly, our research provides embryo models to study cell cycle regulation and DNA damage response under condition of different levels of oxidative stress.

  16. 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

    Chronic unpredictable stress (CUS) is a widely used animal model of depression. The present study was undertaken to investigate behavioral, physiological and molecular effects of CUS and/or chronic antidepressant treatment (venlafaxine or imipramine) in the same set of animals. Anhedonia, a core...

  17. [Chronic stress-related compartment syndrome of the forearm].

    Science.gov (United States)

    Kouvalchouk, J F; Watin Augouard, L; Dufour, O; Coudert, X; Paszkowski, A

    1993-01-01

    The chronic anterior compartment syndrome of the forearm is a rare pathology (3 cases have been already published), and of new knowledge. Three new cases on 2 patients (one on both sides) are described here. The authors describe recent advances about physiopathology, exploration and surgical treatment. It is due to strenuous activity using flexor muscles of the forearm without any release period (here motor cyclist competition). The symptom was pain at the anterior forearm similar to cramp. The most important for diagnosis was to measure the pressure after activity. The threshold level read after activity was up to 30 mm of Hg, with a very slow coming back to normal value. The isotopic scanner with hydroxyl methylene di-phosphonate (HMDP), after activity, showed a delay of arrival of the tracer and a stasis. RMI seems to give abnormal modification of the signal. The only treatment was surgical and an open fasciotomy of superficial and deep fascia must be done, with opening of the muscle's perimysium. The patients became painfree and resumed their sport after surgical treatment.

  18. 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 ...

  19. Upregulation of CB₁ receptor binding in the ventromedial prefrontal cortex promotes proactive stress-coping strategies following chronic stress exposure.

    Science.gov (United States)

    McLaughlin, R J; Hill, M N; Dang, S S; Wainwright, S R; Galea, L A M; Hillard, C J; Gorzalka, B B

    2013-01-15

    Accumulating evidence has revealed that dysregulation of the endocannabinoid system could contribute to the development of major depression. Studies carried out post-mortem in depressed suicide victims have revealed increased CB(1) receptor binding site density in the prefrontal cortex (PFC). Accordingly, exposure of rodents to chronic unpredictable stress (CUS) results in phenotypic changes that mirror those of human depression, including increased CB(1) receptor binding site density in the PFC. Our goal in these