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Sample records for chronic stress selectively

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

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    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.

  2. 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

  3. Chronic combined stress induces selective and long-lasting inflammatory response evoked by changes in corticosterone accumulation and signaling in rat hippocampus.

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    Piskunov, Aleksey; Stepanichev, Mikhail; Tishkina, Anna; Novikova, Margarita; Levshina, Irina; Gulyaeva, Natalia

    2016-04-01

    Hippocampus is believed to be selectively vulnerable to stress. We hypothesized that this phenomenon may be mediated by relatively high vulnerability to neuroinflammation related to impairments of local glucocorticoid metabolism and signaling. We have evaluated inflammatory responses induced by acute or chronic combined stress in the cerebral cortex and hippocampus as well as circulating and brain corticosterone (CS) levels as well as expression of corticosterone target genes. The hippocampus showed higher stress-induced expression of the proinflammatory cytokine IL-1β as compared to the cerebral cortex. A month after the termination of the chronic stress, IL-1β mRNA in the cerebral cortex reached control level, while in the hippocampus it remained significantly increased. Under chronic stress, the maladaptive inflammatory response in hippocampus was accompanied by a significant increase in local CS levels, as compared to cerebral cortex. Under acute stress, the increased CS level induced changes in CS-regulated genes expression (CRF and IGF1), while this phenomenon was not observed after chronic stress. Thus, the hippocampus appears to be more vulnerable to stress-induced inflammation as compared to the neocortex and demonstrates persistent inflammatory response induced by chronic stress. Stress-induced maladaptive inflammatory response is associated with a selective increase in hippocampal CS accumulation and changes in CS signaling.

  4. Glucocorticoids, chronic stress, and obesity.

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    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.

  5. Selective chronic stress-induced in vivo ERK1/2 hyperphosphorylation in medial prefrontocortical dendrites : implications for stress-related cortical pathology?

    NARCIS (Netherlands)

    Trentani, A; Kuipers, SD; Ter Horst, GJ; Den Boer, JA

    2002-01-01

    Stress has been shown to affect brain structural plasticity, promote long-term changes in multiple neurotransmitter systems and cause neuronal atrophy. However, the mechanisms involved in these stress-related neural alterations are still poorly understood. Mitogen-activated protein kinase (MAPK) cas

  6. Chronic stress, cognitive functioning and mental health.

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    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.

  7. Chronic stress and immunosenescence: a review.

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    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.

  8. Neural Control of Chronic Stress Adaptation

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    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.

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

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    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.

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

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    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.

  11. Psychoneuroendocrinological studies on chronic stress and depression.

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    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.

  12. Psychosocial Determinants of Chronic Stress in Nursing

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    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

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

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    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.

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

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    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…

  15. 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.

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

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    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.

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

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    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.

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

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    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

  19. 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...

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

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    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.

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

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

    2011-07-01

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

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

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    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

  3. 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.

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

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    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. Physical activity buffers fatigue only under low chronic stress.

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    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.

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

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    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.

  7. Acute stress selectively impairs learning to act.

    Science.gov (United States)

    de Berker, Archy O; Tirole, Margot; Rutledge, Robb B; Cross, Gemma F; Dolan, Raymond J; Bestmann, Sven

    2016-07-20

    Stress interferes with instrumental learning. However, choice is also influenced by non-instrumental factors, most strikingly by biases arising from Pavlovian associations that facilitate action in pursuit of rewards and inaction in the face of punishment. Whether stress impacts on instrumental learning via these Pavlovian associations is unknown. Here, in a task where valence (reward or punishment) and action (go or no-go) were orthogonalised, we asked whether the impact of stress on learning was action or valence specific. We exposed 60 human participants either to stress (socially-evaluated cold pressor test) or a control condition (room temperature water). We contrasted two hypotheses: that stress would lead to a non-selective increase in the expression of Pavlovian biases; or that stress, as an aversive state, might specifically impact action production due to the Pavlovian linkage between inaction and aversive states. We found support for the second of these hypotheses. Stress specifically impaired learning to produce an action, irrespective of the valence of the outcome, an effect consistent with a Pavlovian linkage between punishment and inaction. This deficit in action-learning was also reflected in pupillary responses; stressed individuals showed attenuated pupillary responses to action, hinting at a noradrenergic contribution to impaired action-learning under stress.

  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. 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.

  10. Acute stress selectively reduces reward sensitivity

    Directory of Open Access Journals (Sweden)

    Lisa H Berghorst

    2013-04-01

    Full Text Available Stress may promote the onset of psychopathology by disrupting reward processing. However, the extent to which stress impairs reward processing, rather than incentive processing more generally, is unclear. To evaluate the specificity of stress-induced reward processing disruption, 100 psychiatrically healthy females were administered a probabilistic stimulus selection task enabling comparison of sensitivity to reward-driven (Go and punishment-driven (NoGo learning under either ‘no stress’ or ‘stress’ (threat-of-shock conditions. Cortisol samples and self-report measures were collected. Contrary to hypotheses, the groups did not differ significantly in task performance or cortisol reactivity. However, further analyses focusing only on individuals under ‘stress’ who were high responders with regard to both cortisol reactivity and self-reported negative affect revealed reduced reward sensitivity relative to individuals tested in the ‘no stress’ condition; importantly, these deficits were reward-specific. Overall, findings provide preliminary evidence that stress-reactive individuals show diminished sensitivity to reward but not punishment under stress. While such results highlight the possibility that stress-induced anhedonia might be an important mechanism linking stress to affective disorders, future studies are necessary to confirm this conjecture.

  11. 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

  12. Chronic psychosocial stress induces visceral hyperalgesia in mice.

    Science.gov (United States)

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

    2012-05-01

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

  13. [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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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...

  1. 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...

  2. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Chronic Stress Facilitates the Development of Deep Venous Thrombosis

    Directory of Open Access Journals (Sweden)

    Tao Dong

    2015-01-01

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

  5. 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

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

    Science.gov (United States)

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

    2016-03-01

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

  7. 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...

  8. 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.

  9. 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).

  10. 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.

  11. [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.

  12. 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.

  13. 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.

  14. Stress-Driven Selection of Novel Phenotypes

    Science.gov (United States)

    Fox, George E.; Stepaov, Victor G.; Liu, Yamei

    2011-01-01

    A process has been developed that can confer novel properties, such as metal resistance, to a host bacterium. This same process can also be used to produce RNAs and peptides that have novel properties, such as the ability to bind particular compounds. It is inherent in the method that the peptide or RNA will behave as expected in the target organism. Plasmid-born mini-gene libraries coding for either a population of combinatorial peptides or stable, artificial RNAs carrying random inserts are produced. These libraries, which have no bias towards any biological function, are used to transform the organism of interest and to serve as an initial source of genetic variation for stress-driven evolution. The transformed bacteria are propagated under selective pressure in order to obtain variants with the desired properties. The process is highly distinct from in vitro methods because the variants are selected in the context of the cell while it is experiencing stress. Hence, the selected peptide or RNA will, by definition, work as expected in the target cell as the cell adapts to its presence during the selection process. Once the novel gene, which produces the sought phenotype, is obtained, it can be transferred to the main genome to increase the genetic stability in the organism. Alternatively, the cell line can be used to produce novel RNAs or peptides with selectable properties in large quantity for separate purposes. The system allows for easy, large-scale purification of the RNAs or peptide products. The process has been reduced to practice by imposing sub-inhibitory concentrations of NiCl2 on cells of the bacterium Escherichia coli that were transformed separately with the peptide library and RNA library. The evolved resistant clones were isolated, and sequences of the selected mini-gene variants were established. Clones resistant to NiCl2 were found to carry identical plasmid variants with a functional mini-gene that specifically conferred significant nickel

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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...

  3. 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.

  4. 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

  5. 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.

  6. 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

  7. 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.

  8. 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.

  9. 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.

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

    Science.gov (United States)

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

    2015-12-03

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

  11. 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.

  12. 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.

  13. Stress coping mechanisms in patients with chronic dermatoses

    Directory of Open Access Journals (Sweden)

    Korabel, Hanna

    2013-09-01

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

  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. A role for motoneuron subtype-selective ER stress in disease manifestations of FALS mice.

    Science.gov (United States)

    Saxena, Smita; Cabuy, Erik; Caroni, Pico

    2009-05-01

    The mechanisms underlying disease manifestations in neurodegeneration remain unclear, but their understanding is critical to devising effective therapies. We carry out a longitudinal analysis in vivo of identified motoneurons selectively vulnerable (VUL) or resistant (RES) to motoneuron disease (amyotrophic lateral sclerosis, ALS) and show that subtype-selective endoplasmic reticulum (ER) stress responses influence disease manifestations. VUL motoneurons were selectively prone to ER stress and showed gradually upregulated ER stress markers from birth on in three mouse models of familial ALS (FALS). 25-30 days before the earliest denervations, ubiquitin signals increased in both VUL and RES motoneurons, but an unfolded protein response coupled with microglial activation was initiated selectively in VUL motoneurons. This transition was followed by selective axonal degeneration and spreading stress. The ER stress-protective agent salubrinal attenuated disease manifestations and delayed progression, whereas chronic enhancement of ER stress promoted disease. Thus, whereas all motoneurons are preferentially affected in ALS, ER stress responses in specific motoneuron subtypes influence the progressive manifestations of weakening and paralysis.

  16. 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.

  17. 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.

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

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    Angélique Favreau-Peigné

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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.

  4. 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.

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

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    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.

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

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    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.

  7. 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

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

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    Ignacio Negrón-Oyarzo

    2016-01-01

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

  9. 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

  10. Occupational Heat Stress Profiles in Selected Workplaces in India

    OpenAIRE

    Vidhya Venugopal; Chinnadurai, Jeremiah S.; Lucas, Rebekah A. I.; Tord Kjellstrom

    2015-01-01

    Health and productivity impacts from occupational heat stress have significant ramifications for the large workforce of India. This study profiled occupational heat stress impacts on the health and productivity of workers in select organized and unorganized Indian work sectors. During hotter and cooler seasons, Wet Bulb Globe Temperatures (WBGT) were used to quantify the risk of heat stress, according to International workplace guidelines. Questionnaires assessed workers' perceived health and...

  11. 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.

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

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    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.

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

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    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.

  14. 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.

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

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    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

  16. 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.

  17. [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.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. Sex-specific selection under environmental stress in seed beetles.

    Science.gov (United States)

    Martinossi-Allibert, I; Arnqvist, G; Berger, D

    2017-01-01

    Sexual selection can increase rates of adaptation by imposing strong selection in males, thereby allowing efficient purging of the mutation load on population fitness at a low demographic cost. Indeed, sexual selection tends to be male-biased throughout the animal kingdom, but little empirical work has explored the ecological sensitivity of this sex difference. In this study, we generated theoretical predictions of sex-specific strengths of selection, environmental sensitivities and genotype-by-environment interactions and tested them in seed beetles by manipulating either larval host plant or rearing temperature. Using fourteen isofemale lines, we measured sex-specific reductions in fitness components, genotype-by-environment interactions and the strength of selection (variance in fitness) in the juvenile and adult stage. As predicted, variance in fitness increased with stress, was consistently greater in males than females for adult reproductive success (implying strong sexual selection), but was similar in the sexes in terms of juvenile survival across all levels of stress. Although genetic variance in fitness increased in magnitude under severe stress, heritability decreased and particularly so in males. Moreover, genotype-by-environment interactions for fitness were common but specific to the type of stress, sex and life stage, suggesting that new environments may change the relative alignment and strength of selection in males and females. Our study thus exemplifies how environmental stress can influence the relative forces of natural and sexual selection, as well as concomitant changes in genetic variance in fitness, which are predicted to have consequences for rates of adaptation in sexual populations.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    Sergiu Dalm

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

  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. Forced degradation studies of biopharmaceuticals: Selection of stress conditions.

    Science.gov (United States)

    Tamizi, Elnaz; Jouyban, Abolghasem

    2016-01-01

    Stability studies under stress conditions or forced degradation studies play an important role in different phases of development and production of biopharmaceuticals and biological products. These studies are mostly applicable to selection of suitable candidates and formulation developments, comparability studies, elucidation of possible degradation pathways and identification of degradation products, as well as, development of stability indicating methods. Despite the integral part of these studies in biopharmaceutical industry, there is no well-established protocol for the selection of stress conditions, timing of stress testing and required extent of degradation. Therefore, due to the present gap in the stability studies guidelines, it is the responsibility of researchers working in academia and biopharmaceutical industry to set up forced degradation experiments that could fulfill all the expectations from the stability studies of biopharmaceuticals under stress conditions. Concerning the importance of the function of desired stress conditions in forced degradation studies, the present review aims to provide a practical summary of the applicable stress conditions in forced degradation studies of biopharmaceuticals according to the papers published in a time period of 1992-2015 giving detailed information about the experimental conditions utilized to induce required stresses.

  8. 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.

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2015-10-15

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

  14. 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

  15. 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.

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

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    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

  17. 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...

  18. Stress improves selective attention towards emotionally neutral left ear stimuli.

    Science.gov (United States)

    Hoskin, Robert; Hunter, M D; Woodruff, P W R

    2014-09-01

    Research concerning the impact of psychological stress on visual selective attention has produced mixed results. The current paper describes two experiments which utilise a novel auditory oddball paradigm to test the impact of psychological stress on auditory selective attention. Participants had to report the location of emotionally-neutral auditory stimuli, while ignoring task-irrelevant changes in their content. The results of the first experiment, in which speech stimuli were presented, suggested that stress improves the ability to selectively attend to left, but not right ear stimuli. When this experiment was repeated using tonal stimuli the same result was evident, but only for female participants. Females were also found to experience greater levels of distraction in general across the two experiments. These findings support the goal-shielding theory which suggests that stress improves selective attention by reducing the attentional resources available to process task-irrelevant information. The study also demonstrates, for the first time, that this goal-shielding effect extends to auditory perception.

  19. 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.

  20. 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.

  1. Differential Impact of Stress Reduction Programs upon Ambulatory Blood Pressure among African American Adolescents: Influences of Endothelin-1 Gene and Chronic Stress Exposure

    Directory of Open Access Journals (Sweden)

    Mathew J. Gregoski

    2012-01-01

    Full Text Available Stress-activated gene × environment interactions may contribute to individual variability in blood pressure reductions from behavioral interventions. We investigated effects of endothelin-1 (ET-1 LYS198ASN SNP and discriminatory stress exposure upon impact of 12-week behavioral interventions upon ambulatory BP (ABP among 162 prehypertensive African American adolescents. Following genotyping, completion of questionnaire battery, and 24-hour ABP monitoring, participants were randomized to health education control (HEC, life skills training (LST, or breathing awareness meditation (BAM. Postintervention ABP was obtained. Significant three-way interactions on ABP changes indicated that among ET-1 SNP carriers, the only group to show reductions was BAM from low chronic stress environments. Among ET-1 SNP noncarriers, under low chronic stress exposure, all approaches worked, especially BAM. Among high stress exposure noncarriers, only BAM resulted in reductions. If these preliminary findings are replicated via ancillary analyses of archival databases and then via efficacy trials, selection of behavioral prescriptions for prehypertensives will be edging closer to being guided by individual's underlying genetic and environmental factors incorporating the healthcare model of personalized preventive medicine.

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

    Directory of Open Access Journals (Sweden)

    Paulo J. Nogueira

    1999-01-01

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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Harmen J Krugers

    2010-07-01

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

  6. The Effectiveness of Mindfulness-Based Stress Reduction on Perceived Pain Intensity and Quality of Life in Patients With Chronic Headache

    OpenAIRE

    Bakhshani, Nour-Mohammad; Amirani, Ahmadreza; Amirifard, Hamed; Shahrakipoor, Mahnaz

    2015-01-01

    The aim of this study was to determine the effectiveness of Mindfulness-Based Stress reduction (MBSR) on perceived pain intensity and quality of life in patients with chronic headache. Thus, forty patients based on the diagnosis of a neurologist and diagnostic criteria of the International Headache Society (IHS) for migraine and chronic tension-type headache were selected and randomly assigned to the intervention group and control group, respectively. The participants completed the Pain and q...

  7. 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.

  8. 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

  9. 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.

  10. Stress selectively affects the reactivated components of a declarative memory.

    Science.gov (United States)

    Hupbach, Almut; Dorskind, Joelle M

    2014-10-01

    When long-term memories are reactivated, they can reenter a transient plastic state in which they are vulnerable to interference or physiological manipulations. The present study attempted to directly affect reactivated memories through a stress manipulation, and compared the effects of stress on reactivated and nonreactivated components of a declarative memory in a within-subject design. We presented image pairs that consisted of an image of an animal and an image of an unrelated object. Participants were instructed to memorize the object images. Forty-eight hours later, we presented half of the animal images again in an unrelated task to indirectly reactivate the associated object images. Immediately after reactivation, participants were exposed to cold pressor stress or a warm water control condition. Forty-eight hours later, we assessed memory for the object images with a free recall test. Reactivation boosted memory performance in the control condition, such that reactivated items were better recalled than nonreactivated items. This memory-enhancing effect of reactivation was completely abolished by cold pressor stress. Importantly, stress selectively impacted only the reactivated items while leaving memory for the nonreactivated items unaffected. The present study shows that it is possible to selectively reactivate and modulate specific parts of a declarative memory.

  11. 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

  12. 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)

  13. 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...

  14. 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.

  15. 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)

  16. 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.

  17. 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.

  18. 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...

  19. 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…

  20. 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.

  1. Influence of Synbiotics on Selected Oxidative Stress Parameters

    Science.gov (United States)

    2017-01-01

    The aim of the present study was to assess synbiotic (Lactobacillus casei + inulin) influence on oxidative stress parameters such as concentrations of malondialdehyde (MDA), hydrogen peroxide (H2O2), glutathione, and free sulfhydryl groups content. Experiments were carried out on healthy volunteers (n = 32). The subjects were divided into women group (n = 16) and men group (n = 16) and randomly assigned to synbiotic and control groups. Blood samples were collected before synbiotic supplementation and after 7 wks, at the end of the study. The administration of synbiotic resulted in a significant decrease in MDA (p inulin may have positive influence on selected oxidative stress markers. PMID:28286605

  2. 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...

  3. Possible role of selective serotonin reuptake inhibitor sertraline on oxidative stress responses.

    Science.gov (United States)

    Battal, D; Yalin, S; Eker, E D; Aktas, A; Sahin, N O; Cebo, M; Berköz, M

    2014-01-01

    The naphthylamine derivative sertraline is a potent and selective inhibitor of serotonin reuptake into presynaptic terminals and the most widely used that has been shown to have both antidepressant and antianxiety effects. In the present study the possible role of sertraline (acute and chronically doses) was evaluated on lipid peroxidation levels and antioxidant enzyme activities in plasma and brain tissues of (10, 40, 80 mg/kg) sertraline treated Wistar albino rats (n=48). Lipid peroxidation levels (MDA) of plasma and brain tissue increased in all acute and chronic sertraline treated rats (p sertraline administration enhances oxidative stress. Therefore, dose adjustment in depression patients seems significant as it may help prevention of further prognosis of the diseases.

  4. Occupational Heat Stress Profiles in Selected Workplaces in India

    Directory of Open Access Journals (Sweden)

    Vidhya Venugopal

    2015-12-01

    Full Text Available Health and productivity impacts from occupational heat stress have significant ramifications for the large workforce of India. This study profiled occupational heat stress impacts on the health and productivity of workers in select organized and unorganized Indian work sectors. During hotter and cooler seasons, Wet Bulb Globe Temperatures (WBGT were used to quantify the risk of heat stress, according to International workplace guidelines. Questionnaires assessed workers’ perceived health and productivity impacts from heat stress. A total of 442 workers from 18 Indian workplaces participated (22% and 78% from the organized and unorganized sector, respectively. Overall 82% and 42% of workers were exposed to higher than recommended WBGT during hotter and cooler periods, respectively. Workers with heavy workloads reported more heat-related health issues (chi square = 23.67, p ≤ 0.001 and reduced productivity (chi square = 15.82, p ≤ 0.001, especially the outdoor workers. Heat-rashes, dehydration, heat-syncope and urinogenital symptoms were self-reported health issues. Cited reasons for productivity losses were: extended-work hours due to fatigue/exhaustion, sickness/hospitalization and wages lost. Reducing workplace heat stress will benefit industries and workers via improving worker health and productivity. Adaptation and mitigation measures to tackle heat stress are imperative to protect the present and future workforce as climate change progresses.

  5. Occupational Heat Stress Profiles in Selected Workplaces in India.

    Science.gov (United States)

    Venugopal, Vidhya; Chinnadurai, Jeremiah S; Lucas, Rebekah A I; Kjellstrom, Tord

    2015-12-29

    Health and productivity impacts from occupational heat stress have significant ramifications for the large workforce of India. This study profiled occupational heat stress impacts on the health and productivity of workers in select organized and unorganized Indian work sectors. During hotter and cooler seasons, Wet Bulb Globe Temperatures (WBGT) were used to quantify the risk of heat stress, according to International workplace guidelines. Questionnaires assessed workers' perceived health and productivity impacts from heat stress. A total of 442 workers from 18 Indian workplaces participated (22% and 78% from the organized and unorganized sector, respectively). Overall 82% and 42% of workers were exposed to higher than recommended WBGT during hotter and cooler periods, respectively. Workers with heavy workloads reported more heat-related health issues (chi square = 23.67, p ≤ 0.001) and reduced productivity (chi square = 15.82, p ≤ 0.001), especially the outdoor workers. Heat-rashes, dehydration, heat-syncope and urinogenital symptoms were self-reported health issues. Cited reasons for productivity losses were: extended-work hours due to fatigue/exhaustion, sickness/hospitalization and wages lost. Reducing workplace heat stress will benefit industries and workers via improving worker health and productivity. Adaptation and mitigation measures to tackle heat stress are imperative to protect the present and future workforce as climate change progresses.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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 ...

  16. 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.

  17. 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.

  18. 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...

  19. 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.

  20. 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.

  1. 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...

  2. 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.

  3. 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.

  4. Response of restraint stress-selected lines of Japanese quail to heat stress and Escherichia coli challenge

    Science.gov (United States)

    Japanese quail selected for divergent corticosterone (Cort) response to restraint stress were evaluated for their susceptibility to heat stress and challenge with Escherichia coli. These quail lines are designated as the high stress (HS), low stress (LS), and the random-bred control (CS) lines. Hea...

  5. 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.

  6. 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

  7. Transcriptome comparison in the pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

    Science.gov (United States)

    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Nie, Qinghua

    2015-10-01

    Chronic stress can induce a series of maladjustments, and the response to stress is partly regulated by the hypothalamus-pituitary-adrenal axis. The aim of this study was to investigate the genetic mechanisms of this axis regulating stress responsiveness. The pituitary and adrenal cortex of Beagle and Chinese Field Dog (CFD) from a stress exposure group [including Beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), Beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)] and a control group [including Beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), Beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)], selected to perform RNA-seq transcriptome comparisons, showed that 40, 346, 376, 69, 70, 38, 57 and 71 differentially expressed genes were detected in BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1, BP2 vs. CFDP2, BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2 respectively. NPB was a gene common to BAC1 vs. BAC2 and CFDAC1 vs. CFDAC2, indicating it was a potential gene affecting response to chronic stress, regardless of the extent of chronic stress induced. PLP1 was a gene common to BP1 vs. CFDP1 and BP2 vs. CFDP2, suggesting its important roles in affecting the stress-tolerance difference between the two breeds, regardless of whether there was stress exposure or not. Pathway analysis found 12, 4, 11 and 1 enriched pathway in the comparisons of BP1 vs. CFDP1, BP2 vs. CFDP2, CFDP1 vs. CFDP2 and BAC1 vs. BAC2 respectively. Glutamatergic synapse, neuroactive ligand-receptor interaction, retrograde endocannabinoid signaling, GABAergic synapse, calcium signaling pathway and dopaminergic synapse were the most significantly enriched pathways in both CFDP1 vs. CFDP2 and BP1 vs. CFDP1. GO, KEGG pathway and gene network analysis demonstrated that GRIA3, GRIN2A, GRIN2B and NPY were important in regulating the stress response in CFD. Nevertheless, ADORA1, CAMK2A, GRM1, GRM7 and NR4A1 might be critical genes contributing to the stress

  8. 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.

  9. 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.

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. 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.

  13. Selective neuronal vulnerability to oxidative stress in the brain

    Directory of Open Access Journals (Sweden)

    Xinkun Wang

    2010-03-01

    Full Text Available Oxidative stress (OS, caused by the imbalance between the generation and detoxification of reactive oxygen and nitrogen species (ROS/RNS, plays an important role in brain aging, neurodegenerative diseases, and other related adverse conditions, such as ischemia. While ROS/RNS serve as signaling molecules at physiological levels, an excessive amount of these molecules leads to oxidative modification and, therefore, dysfunction of proteins, nucleic acids, and lipids. The response of neurons to this pervasive stress, however, is not uniform in the brain. While many brain neurons can cope with a rise in OS, there are select populations of neurons in the brain that are vulnerable. Because of their selective vulnerability, these neurons are usually the first to exhibit functional decline and cell death during normal aging, or in age-associated neurodegenerative diseases, such as Alzheimer’s disease. Understanding the molecular and cellular mechanisms of selective neuronal vulnerability (SNV to OS is important in the development of future intervention approaches to protect such vulnerable neurons from the stresses of the aging process and the pathological states that lead to neurodegeneration. In this review, the currently known molecular and cellular factors that contribute to SNV to OS are summarized. Included among the major underlying factors are high intrinsic OS, high demand for ROS/RNS-based signaling, low ATP production, mitochondrial dysfunction, and high inflammatory response in vulnerable neurons. The contribution to the selective vulnerability of neurons to OS by other intrinsic or extrinsic factors, such as deficient DNA damage repair, low calcium-buffering capacity, and glutamate excitotoxicity, are also discussed.

  14. 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.

  15. 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.

  16. 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.

  17. Impact of Chronic Stress Protocols in Learning and Memory in Rodents: Systematic Review and Meta-Analysis

    Science.gov (United States)

    Moreira, Pedro Silva; Almeida, Pedro R; Leite-Almeida, Hugo; Sousa, Nuno; Costa, Patrício

    2016-01-01

    The idea that maladaptive stress impairs cognitive function has been a cornerstone of decades in basic and clinical research. However, disparate findings have reinforced the need to aggregate results from multiple sources in order to confirm the validity of such statement. In this work, a systematic review and meta-analyses were performed to aggregate results from rodent studies investigating the impact of chronic stress on learning and memory. Results obtained from the included studies revealed a significant effect of stress on global cognitive performance. In addition, stressed rodents presented worse consolidation of learned memories, although no significantly differences between groups at the acquisition phase were found. Despite the methodological heterogeneity across studies, these effects were independent of the type of stress, animals’ strains or age. However, our findings suggest that stress yields a more detrimental effect on spatial navigation tests’ performance. Surprisingly, the vast majority of the selected studies in this field did not report appropriate statistics and were excluded from the quantitative analysis. We have therefore purposed a set of guidelines termed PROBE (Preferred Reporting Orientations for Behavioral Experiments) to promote an adequate reporting of behavioral experiments. PMID:27662580

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. 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

  4. 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

  5. Multitemporal spectroscopy for crop stress detection using band selection methods

    Science.gov (United States)

    Mewes, Thorsten; Franke, Jonas; Menz, Gunter

    2008-08-01

    A fast and precise sensor-based identification of pathogen infestations in wheat stands is essential for the implementation of site-specific fungicide applications. Several works have shown possibilities and limitations for the detection of plant stress using spectral sensor data. Hyperspectral data provide the opportunity to collect spectral reflectance in contiguous bands over a broad range of the electromagnetic spectrum. Individual phenomena like the light absorption of leaf pigments can be examined in detail. The precise knowledge of stress-dependent shifting in certain spectral wavelengths provides great advantages in detecting fungal infections. This study focuses on band selection techniques for hyperspectral data to identify relevant and redundant information in spectra regarding a detection of plant stress caused by pathogens. In a laboratory experiment, five 1 sqm boxes with wheat were multitemporarily measured by a ASD Fieldspec® 3 FR spectroradiometer. Two stands were inoculated with Blumeria graminis - the pathogen causing powdery mildew - and one stand was used to simulate the effect of water deficiency. Two stands were kept healthy as control stands. Daily measurements of the spectral reflectance were taken over a 14-day period. Three ASD Pro Lamps were used to illuminate the plots with constant light. By applying band selection techniques, the three types of different wheat vitality could be accurately differentiated at certain stages. Hyperspectral data can provide precise information about pathogen infestations. The reduction of the spectral dimension of sensor data by means of band selection procedures is an appropriate method to speed up the data supply for precision agriculture.

  6. 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

  7. 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

  8. 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.

  9. 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.

  10. Differences in maladaptive schemas between patients suffering from chronic and acute posttraumatic stress disorder and healthy controls

    Directory of Open Access Journals (Sweden)

    Ahmadian A

    2015-07-01

    Full Text Available Alireza Ahmadian,1,2 Jafar Mirzaee,1 Maryam Omidbeygi,1 Edith Holsboer-Trachsler,3 Serge Brand3,41Department of Psychology, Kharazmi University, 2Sadr Psychiatric Hospital, Janbazan Medical and Engineering Research Center (JMERC, Tehran, Iran; 3Psychiatric Clinics of the University of Basel, Center for Affective, Stress and Sleep Disorders, 4Department of Sport, Exercise and Health, Sport Science Section, University of Basel, Basel, Switzerland Background: War, as a stressor event, has a variety of acute and chronic negative consequences, such as posttraumatic stress disorder (PTSD. In this context, early maladaptive schema-based problems in PTSD have recently become an important research area. The aim of this study was to assess early maladaptive schemas in patients with acute and chronic PTSD.Method: Using available sampling methods and diagnostic criteria, 30 patients with chronic PTSD, 30 patients with acute PTSD, and 30 normal military personnel who were matched in terms of age and wartime experience were selected and assessed with the Young Schema Questionnaire-Long Form, Beck Depression Inventory second version (BDI-II, the Beck Anxiety Inventory (BAI, and the Impact of Events Scale (IES.Results: Both acute and chronic PTSD patients, when compared with normal military personnel, had higher scores for all early maladaptive schemas. Additionally, veterans suffering from chronic PTSD, as compared with veterans suffering from acute PTSD and veterans without PTSD, reported more impaired schemas related, for instance, to Self-Control, Social Isolation, and Vulnerability to Harm and Illness.Discussion: The results of the present study have significant preventative, diagnostic, clinical, research, and educational implications with respect to PTSD. Keywords: veterans, PTSD, depression, anxiety 

  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. 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...

  13. 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.

  14. 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.

  15. 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...

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

    Science.gov (United States)

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

    2013-01-01

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

  17. 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

  18. 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...

  19. 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.

  20. 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

  1. 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...

  2. 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

  3. 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.

  4. 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...

  5. 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.

  6. 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.

  7. 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.

  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. 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.

  12. 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.

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

    Science.gov (United States)

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

    2013-02-01

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

  14. 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...

  15. [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.

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

    OpenAIRE

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

    2010-01-01

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

  17. 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 studies was to examine the effects of CUS on the density of CB(1) receptor binding sites in the rodent medial PFC and to explore the role of this alteration in the behavioral changes invoked by CUS. Rodents exposed to CUS exhibited increased CB(1) receptor maximal binding site density (B(max)) within the ventromedial PFC, but not the dorsomedial PFC. To determine whether this change in the ventromedial PFC is an adaptive response, or alternatively, a consequence of chronic stress that contributes to the adoption of passive coping, we examined whether local CB(1) receptor blockade within the ventromedial PFC following CUS would significantly alter behaviors in the forced swim test (FST). CUS exposure significantly increased passive coping in the FST, and this was further augmented by discrete ventromedial PFC microinfusions of the CB(1) receptor antagonist AM251 prior to swim stress. Moreover, local CB(1) receptor blockade reduced active coping responses in CUS-exposed rats. These findings suggest that the increase in CB(1) receptor B(max) observed in the ventromedial PFC of rodents exposed to CUS maintains proactive coping strategies following chronic stress exposure.

  18. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress.

    Science.gov (United States)

    Rowson, Sydney A; Harrell, Constance S; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J; Kelly, Sean D; Reddy, Renuka; Neigh, Gretchen N

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  19. Neuroinflammation and Behavior in HIV-1 Transgenic Rats Exposed to Chronic Adolescent Stress

    Science.gov (United States)

    Rowson, Sydney A.; Harrell, Constance S.; Bekhbat, Mandakh; Gangavelli, Apoorva; Wu, Matthew J.; Kelly, Sean D.; Reddy, Renuka; Neigh, Gretchen N.

    2016-01-01

    Highly active antiretroviral therapy (HAART) has improved prognosis for people living with HIV (PLWH) and dramatically reduced the incidence of AIDS. However, even when viral load is controlled, PLWH develop psychiatric and neurological disorders more frequently than those living without HIV. Adolescents with HIV are particularly susceptible to the development of psychiatric illnesses and neurocognitive impairments. While both psychiatric and neurocognitive disorders have been found to be exacerbated by stress, the extent to which chronic stress and HIV-1 viral proteins interact to impact behavior and relevant neuroinflammatory processes is unknown. Determination of the individual contributions of stress and HIV to neuropsychiatric disorders is heavily confounded in humans. In order to isolate the influence of HIV-1 proteins and chronic stress on behavior and neuroinflammation, we employed the HIV-1 transgenic (Tg) rat model, which expresses HIV-1 proteins with a gag and pol deletion, allowing for viral protein expression without viral replication. This Tg line has been characterized as a model of HAART-controlled HIV-1 infection due to the lack of viral replication but continued presence of HIV-1 proteins. We exposed male and female adolescent HIV-1 Tg rats to a mixed-modality chronic stress paradigm consisting of isolation, social defeat and restraint, and assessed behavior, cerebral vascularization, and neuroinflammatory endpoints. Stress, sex, and presence of the HIV-1 transgene impacted weight gain in adolescent rats. Female HIV-1 Tg rats showed decreases in central tendency during the light cycle in the open field regardless of stress exposure. Both male and female HIV-1 Tg rats exhibited decreased investigative behavior in the novel object recognition task, but no memory impairments. Adolescent stress had no effect on the tested behaviors. Microglia in female HIV-1 Tg rats exhibited a hyper-ramified structure, and gene expression of complement factor B was

  20. Increased Oxidative Stress as a Selective Anticancer Therapy

    Directory of Open Access Journals (Sweden)

    Jiahui Liu

    2015-01-01

    Full Text Available Reactive oxygen species (ROS are closely related to tumorgenesis. Under hypoxic environment, increased levels of ROS induce the expression of hypoxia inducible factors (HIFs in cancer stem cells (CSCs, resulting in the promotion of the upregulation of CSC markers, and the reduction of intracellular ROS level, thus facilitating CSCs survival and proliferation. Although the ROS level is regulated by powerful antioxidant defense mechanisms in cancer cells, it is observed to remain higher than that in normal cells. Cancer cells may be more sensitive than normal cells to the accumulation of ROS; consequently, it is supposed that increased oxidative stress by exogenous ROS generation therapy has an effect on selectively killing cancer cells without affecting normal cells. This paper reviews the mechanisms of redox regulation in CSCs and the pivotal role of ROS in anticancer treatment.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Zehra Serdar

    2003-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Dewi-Nurul M Dewi-Nurul

    2006-04-01

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

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

    Directory of Open Access Journals (Sweden)

    Asfandyar Khan Niazi

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Asfandyar Khan Niazi

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    M. Surekha Bhat

    2007-01-01

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

  7. Housing in pyramid counteracts neuroendocrine and oxidative stress caused by chronic restraint in rats.

    Science.gov (United States)

    Bhat, M Surekha; Rao, Guruprasad; Murthy, K Dilip; Bhat, P Gopalakrishna

    2007-03-01

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

  8. Electroacupuncture pretreatment exhibits anti-depressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

    Institute of Scientific and Technical Information of China (English)

    Zhuo Guo; Xu-hui Zhang; Ya Tu; Tian-wei Guo; Yun-chu Wu; Xue-qin Yang; Lan Sun; Xin-jing Yang; Wen-yue Zhang; Yu Wang

    2015-01-01

    The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and elec-troacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment atBaihui (GV20) andYintang (GV29) acupoints was per-formed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes) prior to restraint for 28 days. Open ifeld tests and body weight measurements were carried out to evaluate the depressive symptoms at speciifc time points. On day 28, the crossing number, rearing number, and body weights of the model group were signiifcantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and abso-lute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins (COG) database. Twenty-seven differential pro-teins (uncharacteristic proteins expected) were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related proteins

  9. Electroacupuncture pretreatment exhibits anti-depressive effects by regulating hippocampal proteomics in rats with chronic restraint stress

    Directory of Open Access Journals (Sweden)

    Zhuo Guo

    2015-01-01

    Full Text Available The clinical effect of electroacupuncture on depression is widely recognized. However, the signal transduction pathways and target proteins involved remain unclear. In the present study, rat models of chronic restraint stress were used to explore the mechanism by which electroacupuncture alleviates depression. Rats were randomly divided into control, model, and electroacupuncture groups. Chronic restraint stress was induced in the model and electroacupuncture groups by restraining rats for 28 days. In the electroacupuncture group, electroacupuncture pretreatment at Baihui (GV20 and Yintang (GV29 acupoints was performed daily (1 mA, 2 Hz, discontinuous wave, 20 minutes prior to restraint for 28 days. Open field tests and body weight measurements were carried out to evaluate the depressive symptoms at specific time points. On day 28, the crossing number, rearing number, and body weights of the model group were significantly lower than those in the control group. Behavior test results indicated that rat models of depressive-like symptoms were successfully established by chronic restraint stress combined with solitary raising. On day 28, an isobaric tag for a relative and absolute quantitation-based quantitative proteomic approach was performed to identify differentially expressed proteins in hippocampal samples obtained from the model and electroacupuncture groups. The potential function of these differential proteins was predicted through the use of the Cluster of Orthologous Groups of proteins (COG database. Twenty-seven differential proteins (uncharacteristic proteins expected were selected from the model and electroacupuncture groups. In addition to unknown protein functions, COG are mainly concentrated in general prediction function, mechanism of signal transduction, amino acid transport and metabolism groups. This suggests that electroacupuncture improved depressive-like symptoms by regulating differential proteins, and most of these related

  10. Diagnosis of Chronic Kidney Disease Based on Support Vector Machine by Feature Selection Methods.

    Science.gov (United States)

    Polat, Huseyin; Danaei Mehr, Homay; Cetin, Aydin

    2017-04-01

    As Chronic Kidney Disease progresses slowly, early detection and effective treatment are the only cure to reduce the mortality rate. Machine learning techniques are gaining significance in medical diagnosis because of their classification ability with high accuracy rates. The accuracy of classification algorithms depend on the use of correct feature selection algorithms to reduce the dimension of datasets. In this study, Support Vector Machine classification algorithm was used to diagnose Chronic Kidney Disease. To diagnose the Chronic Kidney Disease, two essential types of feature selection methods namely, wrapper and filter approaches were chosen to reduce the dimension of Chronic Kidney Disease dataset. In wrapper approach, classifier subset evaluator with greedy stepwise search engine and wrapper subset evaluator with the Best First search engine were used. In filter approach, correlation feature selection subset evaluator with greedy stepwise search engine and filtered subset evaluator with the Best First search engine were used. The results showed that the Support Vector Machine classifier by using filtered subset evaluator with the Best First search engine feature selection method has higher accuracy rate (98.5%) in the diagnosis of Chronic Kidney Disease compared to other selected methods.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  12. Effects of acute and chronic physical exercise and stress on different types of memory in rats.

    Science.gov (United States)

    Mello, Pâmela Billig; Benetti, Fernando; Cammarota, Martín; Izquierdo, Iván

    2008-06-01

    Here we study the effect of acute and chronic physical exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress) during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests employed were: habituation in an open field, object recognition and spatial learning in the Morris water maze. Daily foot-shock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM) and long-term memory (LTM) of the recognition task at 2 weeks but only STM after 8 weeks and had no effect on spatial learning after either 2 or 8 weeks. Acute but not chronic exercise also enhanced habituation in the open field and hindered STM and LTM in the recognition task. Chronic exercise enhanced one important measure of spatial learning (latency to escape) but not others. Our findings indicate that some care must be taken when interpreting effects of forced exercise on brain parameters since at least part of them may be due to the stress inherent to the training procedure.

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

    Science.gov (United States)

    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.

  14. Comparison of oxidative stress biomarker profiles between acute and chronic wound environments.

    Science.gov (United States)

    Moseley, Ryan; Hilton, Joanna R; Waddington, Rachel J; Harding, Keith G; Stephens, Phil; Thomas, David W

    2004-01-01

    Increasing evidence implicates excessive reactive oxygen species (ROS) generation and ROS-derived degradation products in the pathogenesis of many skin diseases. While numerous attempts have been made to identify prognostic biomarkers of wound healing in skin, these have met with limited success. This study examined the profiles of various oxidative stress biomarkers, namely total protein carbonyl content (from protein oxidation), malondialdehyde content (from lipid peroxidation), and the total antioxidant capacities, in acute wound fluid (n= 10) and chronic wound fluid (n= 12), using a rapid, noninvasive collection technique. Protein carbonyl content was quantified spectrophotometrically and by sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blotting, following 2,4-dinitrophenylhydrazine derivitization. Malondialdehyde levels were similarly quantified, following N-methyl-2-phenylindole derivitization. Total antioxidant capacity was determined via wound fluid inhibition of cytochrome C reduction by a superoxide radical flux. Acute wound fluid contained higher protein carbonyl content than chronic wound fluid, particularly evident following sodium dodecyl sulfate-polyacrylamide gel electrophoresis/Western blot analysis under nonreducing and reducing conditions (p oxidized in both acute and chronic wound fluid, which may contribute to the reduced albumin and total protein levels in chronic wound fluid. No significant difference (p > 0.1) in malondialdehyde levels or total antioxidant capacities were determined between acute and chronic wound fluids, although chronic wound fluid exhibited significantly higher total antioxidant capacities (p < 0.005), accounting for variations in wound fluid protein content. These findings suggest an adaptation in the antioxidant profiles of chronic wound fluid to counteract the loss of consumed antioxidants in the chronic wound environment. This study highlights the roles of ROS/antioxidants in skin wound healing

  15. Caffeine prevents cognitive impairment induced by chronic psychosocial stress and/or high fat-high carbohydrate diet.

    Science.gov (United States)

    Alzoubi, K H; Abdul-Razzak, K K; Khabour, O F; Al-Tuweiq, G M; Alzubi, M A; Alkadhi, K A

    2013-01-15

    Caffeine alleviates cognitive impairment associated with a variety of health conditions. In this study, we examined the effect of caffeine treatment on chronic stress- and/or high fat-high carbohydrate Western diet (WD)-induced impairment of learning and memory in rats. Chronic psychosocial stress, WD and caffeine (0.3 g/L in drinking water) were simultaneously administered for 3 months to adult male Wistar rats. At the conclusion of the 3 months, and while the previous treatments continued, rats were tested in the radial arm water maze (RAWM) for learning, short-term and long-term memory. This procedure was applied on a daily basis to all animals for 5 consecutive days or until the animal reaches days to criterion (DTC) in the 12th learning trial and memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Chronic stress and/or WD groups caused impaired learning, which was prevented by chronic caffeine administration. In the memory tests, chronic caffeine administration also prevented memory impairment during chronic stress conditions and/or WD. Furthermore, DTC value for caffeine treated stress, WD, and stress/WD groups indicated that caffeine normalizes memory impairment in these groups. These results showed that chronic caffeine administration prevented stress and/or WD-induced impairment of spatial learning and memory.

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

    Science.gov (United States)

    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.

  17. Unpredictable chronic stress-induced reproductive suppression associated with the decrease of kisspeptin immunoreactivity in male mice.

    Science.gov (United States)

    Hirano, Tetsushi; Kobayashi, Yoshihiro; Omotehara, Takuya; Tatsumi, Atsutoshi; Hashimoto, Rie; Umemura, Yuria; Nagahara, Daichi; Mantani, Youhei; Yokoyama, Toshifumi; Kitagawa, Hiroshi; Hoshi, Nobuhiko

    2014-09-01

    Environmental stress affects various parts of mammals typically through the circulation of stress hormones. It has been identified as one of the possible reasons for male reproductive difficulties, but the complex mechanisms responsible for stress-induced reproductive suppression are poorly understood. Here, we examined the relationship between chronic environmental stress and hypothalamic kisspeptin, a recently discovered upstream regulator of the reproductive endocrine feedback system. We studied male mice under an unpredictable chronic stress procedure to replicate the situation of animals under chronic stress. Histological and immunohistochemical analyses were performed focusing on kisspeptin neurons in the arcuate hypothalamic nucleus (ARC) and DNA fragmented cells in seminiferous tubules. Although the ARC was not morphologically altered in either the stressed or non-stressed group, granular kisspeptin immunoreactivities decreased slightly in the stress group. In the testes of the stress group, several signs of testicular degeneration were observed, including increased numbers of ssDNA-positive cells per seminiferous tubule, thinning, vacuoled seminiferous epithelia and multinucleated giant cells. The decreases in kisspeptin in the stress group might be due to other hypothalamic peptides, such as corticotropin-releasing hormone and leptin, whose receptors are known to coexpress in the ARC. In addition, environmental stress directly and indirectly affects testicular function through stress hormones and gonadotropins. In summary, our findings enhance the understanding of stress-induced reproductive suppression possibly mediated by kisspeptin in the ARC.

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

    Directory of Open Access Journals (Sweden)

    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.

  19. 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

  20. Orexin administration to mice that underwent chronic stress produces bimodal effects on emotion-related behaviors.

    Science.gov (United States)

    Chung, Hye-Seung; Kim, Jae-Gon; Kim, Jae-Won; Kim, Hyung-Wook; Yoon, Bong-June

    2014-11-01

    Orexin plays diverse roles in regulating behaviors, such as sleep and wake, reward processing, arousal, and stress and anxiety. The orexin system may accomplish these multiple tasks through its complex innervations throughout the brain. The emerging evidence indicates a role of orexin in emotional behaviors; however, most of the previous studies have investigated the function of orexin in naïve animals. Here, we examined a functional role of orexin in mice that had been exposed to repeated stress. Chronic social defeat stress produced differential social interaction behaviors in mice (susceptible versus resilient) and these two groups of mice displayed different levels of prepro-orexin in the hypothalamus. Exogenously added orexin A to the brain induced an antidepressant-like effect in only the susceptible mice but not in the resilient mice. In contrast, orexin A and orexin B infused together produced an anxiogenic effect in only the resilient mice and not in the susceptible mice. Furthermore, we found that the antidepressant-like effect of orexin A is mediated by the bed nucleus of the stria terminalis (BNST) after exposure to chronic restraint stress. These findings reveal a bimodal effect of the orexin system in regulating emotional behavior that depends on stress susceptibility.

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

    Science.gov (United States)

    Bergmann, N; Gyntelberg, F; Faber, J

    2014-06-01

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

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

    Science.gov (United States)

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

    2006-04-01

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

  3. 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.

  4. 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.

  5. 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.

  6. Self-Inflicted Burns in Patients with Chronic Combat-Related Post-Traumatic Stress Disorder

    OpenAIRE

    Braš, Marijana; Lončar, Zoran; Boban, Maja; Gregurek, Rudolf; Brajković, Lovorka; Tomičić, Hrvoje; Muljačić, Ante; Mičković, Vlatko; Kalenić, Barbara

    2007-01-01

    This study examined self-inflicted burns in case series of four patients with chronic combat-related post-traumatic stress disorder (PTSD). Those patients were hospitalized in the Burn Unit of the University Hospital of Traumatology in Zagreb because of severe burns and had a premorbid psychiatric history of PTSD. Demographic data and information regarding the circumstances surrounding the incident, burn severity, treatment and outcomes of these patients were collected. The author...

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

    Institute of Scientific and Technical Information of China (English)

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

    2006-01-01

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

  8. Chronic sleep loss during pregnancy as a determinant of stress: impact on pregnancy outcome.

    Science.gov (United States)

    Palagini, Laura; Gemignani, Angelo; Banti, Susanna; Manconi, Mauro; Mauri, Mauro; Riemann, Dieter

    2014-08-01

    Short sleep duration, poor sleep quality, and insomnia frequently characterize sleep in pregnancy during all three trimesters. We aimed: (i) to review the clinical evidence of the association between conditions of sleep loss during pregnancy and adverse pregnancy outcomes; and (ii) to discuss the potential pathophysiological mechanisms that may be involved. A systematic search of cross-sectional, longitudinal studies using Medline, Embase, and PsychINFO, and MeSH headings and key words for conditions of sleep loss such as 'insomnia', 'poor sleep quality', 'short sleep duration', and 'pregnancy outcome' was made for papers published between January 1, 1960 and July 2013. Twenty studies met inclusion criteria for sleep loss and pregnancy outcome: seven studies on prenatal depression, three on gestational diabetes, three on hypertension, pre-eclampsia/eclampsia, six on length of labor/type of delivery, eight on preterm birth, and three on birth grow/birth weight. Two main results emerged: (i) conditions of chronic sleep loss are related to adverse pregnancy outcomes; and (ii) chronic sleep loss yields a stress-related hypothalamic-pituitary-adrenal axis and abnormal immune/inflammatory, reaction, which, in turn, influences pregnancy outcome negatively. Chronic sleep loss frequently characterizes sleep throughout the course of pregnancy and may contribute to adverse pregnancy outcomes. Common pathophysiological mechanisms emerged as being related to stress system activation. We propose that in accordance to the allostatic load hypothesis, chronic sleep loss during pregnancy may also be regarded as both a result of stress and a physiological stressor per se, leading to stress 'overload'. It may account for adverse pregnancy outcomes and somatic and mental disorders in pregnancy.

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

    Science.gov (United States)

    Eggers, Arnold E

    2007-01-01

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

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Li-Juan Zhu

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

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

    Indian Academy of Sciences (India)

    Ashok Iyyaswamy; Sheeladevi Rathinasamy

    2012-09-01

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

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

    Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

    2012-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Lauren E Chaby

    Full Text Available Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

  16. 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.

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

    Science.gov (United States)

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

    2015-01-01

    Spatial abilities allow animals to retain and cognitively manipulate information about their spatial environment and are dependent upon neural structures that mature during adolescence. Exposure to stress in adolescence is thought to disrupt neural maturation, possibly compromising cognitive processes later in life. We examined whether exposure to chronic unpredictable stress in adolescence affects spatial ability in late adulthood. We evaluated spatial learning, reference and working memory, as well as long-term retention of visuospatial cues using a radial arm water maze. We found that stress in adolescence decreased the rate of improvement in spatial learning in adulthood. However, we found no overall performance impairments in adult reference memory, working memory, or retention caused by adolescent-stress. Together, these findings suggest that adolescent-stress may alter the strategy used to solve spatial challenges, resulting in performance that is more consistent but is not refined by incorporating available spatial information. Interestingly, we also found that adolescent-stressed rats showed a shorter latency to begin the water maze task when re-exposed to the maze after an overnight delay compared with control rats. This suggests that adolescent exposure to reoccurring stressors may prepare animals for subsequent reoccurring challenges. Overall, our results show that stress in adolescence does not affect all cognitive processes, but may affect cognition in a context-dependent manner.

  18. Effect of chronic restraint stress on human colorectal carcinoma growth in mice.

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    Qiang Lin

    Full Text Available Stress alters immunological and neuroendocrinological functions. An increasing number of studies indicate that chronic stress can accelerate tumor growth, but its role in colorectal carcinoma (CRC progression is not well understood. The aim of this study is to investigate the effects of chronic restraint stress (CRS on CRC cell growth in nude mice and the possible underlying mechanisms. In this study, we showed that CRS increased the levels of plasma catecholamines including epinephrine (E and norepinephrine (NE, and stimulated the growth of CRC cell-derived tumors in vivo. Treatment with the adrenoceptor (AR antagonists phentolamine (PHE, α-AR antagonist and propranolol (PRO, β-AR antagonist significantly inhibited the CRS-enhanced CRC cell growth in nude mice. In addition, the stress hormones E and NE remarkably enhanced CRC cell proliferation and viability in culture, as well as tumor growth in vivo. These effects were antagonized by the AR antagonists PHE and PRO, indicating that the stress hormone-induced CRC cell proliferation is AR dependent. We also observed that the β-AR antagonists atenolol (ATE, β1- AR antagonist and ICI 118,551 (ICI, β2- AR antagonist inhibited tumor cell proliferation and decreased the stress hormone-induced phosphorylation of extracellular signal-regulated kinases-1/2 (ERK1/2 in vitro and in vivo. The ERK1/2 inhibitor U0126 also blocked the function of the stress hormone, suggesting the involvement of ERK1/2 in the tumor-promoting effect of CRS. We conclude that CRS promotes CRC xenograft tumor growth in nude mice by stimulating CRC cell proliferation through the AR signaling-dependent activation of ERK1/2.

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

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    Levente Kovács

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

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

    Directory of Open Access Journals (Sweden)

    Yang P

    2015-03-01

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

  1. Sex differences in subcellular distribution of delta opioid receptors in the rat hippocampus in response to acute and chronic stress

    OpenAIRE

    Sanoara Mazid; Hall, Baila S.; Odell, Shannon C.; Khalifa Stafford; Dyer, Andreina D.; Van Kempen, Tracey A.; Jane Selegean; McEwen, Bruce S.; Elizabeth M. Waters; Milner, Teresa A.

    2016-01-01

    Drug addiction requires associative learning processes that critically involve hippocampal circuits, including the opioid system. We recently found that acute and chronic stress, important regulators of addictive processes, affect hippocampal opioid levels and mu opioid receptor trafficking in a sexually dimorphic manner. Here, we examined whether acute and chronic stress similarly alters the levels and trafficking of hippocampal delta opioid receptors (DORs). Immediately after acute immobili...

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

    Science.gov (United States)

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

    2013-12-03

    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.

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

    Science.gov (United States)

    Chhillar, Ritu; Dhingra, Dinesh

    2013-08-01

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

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

    Science.gov (United States)

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

    2012-07-01

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

  6. Learning, memory, and glial cell changes following recovery from chronic unpredictable stress.

    Science.gov (United States)

    Bian, Yanqing; Pan, Zhuo; Hou, Ziyuan; Huang, Cui; Li, Wei; Zhao, Baohua

    2012-08-01

    Previous research has indicated that chronic stress induces inflammatory responses, cognitive impairments, and changes in microglia and astrocytes. However, whether stress-induced changes following recovery are reversible is unclear. The present study examined the effects of chronic unpredictable stress (CUS) following recovery on spatial learning and memory impairments, changes in microglia and astrocytes, and interleukine-1β (IL-1β) and glial-derived neurotrophic factor (GDNF) levels. Mice were randomly divided into control, stress, and recovery groups, and CUS was applied to mice in the stress and recovery groups for 40 days. Following the application of CUS, the recovery group was allowed 40 days without stress. The results of the Morris water maze illustrated that CUS-induced spatial learning and memory impairments could be reversed or even improved by a period of recovery. Immunohistochemical tests revealed that CUS-induced alterations in microglia could dissipate with time in the CA3 region of the hippocampus and prelimbic areas. However, CUS-induced activation of astrocytes was sustained in the CA3 area following recovery. Western blot analyses revealed that CUS induced a significant increase of GDNF and a significant decrease in IL-1β. Additionally, increased GDNF levels were sustained in the hippocampus during recovery. In conclusion, this study provides evidence that CUS-induced learning and memory impairments could be reversible following recovery. However, activated astrocytes and increased GDNF levels in the hippocampus remained elevated after recovery, suggesting that activated astrocytes and increased GDNF play important roles in the adaptation of the brain to CUS and in repairing CUS-induced impairments during recovery.

  7. Effect of Spirulina Intervention on Oxidative Stress, Antioxidant Status, and Lipid Profile in Chronic Obstructive Pulmonary Disease Patients

    Science.gov (United States)

    Ismail, Md.; Hossain, Md. Faruk; Tanu, Arifur Rahman

    2015-01-01

    Background and Objective. Oxidative stress is intimately associated with many diseases, including chronic obstructive pulmonary disease (COPD). Study objectives include a comparison of the oxidative stress, antioxidant status, and lipid profile between COPD patients and controls and evaluation of the effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile of COPD patients. Methods. 30 patients with COPD and 20 controls with no respiratory problems were selected. Global Initiative for Chronic Obstructive Lung Disease criteria were served as the basis of COPD diagnosis. The serum content of malondialdehyde (MDA), lipid hydroperoxide, glutathione (GSH), vitamin C, cholesterol, triglyceride (TG), and high density lipoprotein (HDL) was measured. The activity of superoxide dismutase (SOD), catalase (CAT), and glutathione-s-transferase (GST) was also measured. Two different doses, (500 × 2) mg and (500 × 4) mg spirulina, were given to two groups, each of which comprises 15 COPD patients. Results. All targeted blood parameters have significant difference (P = 0.000) between COPD patients and controls except triglyceride (TG). Spirulina intake for 30 and 60 days at (500 × 2) mg dose has significantly reduced serum content of MDA, lipid hydroperoxide, and cholesterol (P = 0.000) while increasing GSH, Vit C level (P = 0.000), and the activity of SOD (P = 0.000) and GST (P = 0.038). At the same time, spirulina intake for 30 and 60 days at (500 × 4) mg dose has favorable significant effect (P = 0.000) on all targeted blood parameters except for HDL (P = 0.163). PMID:25685791

  8. Effect of Spirulina Intervention on Oxidative Stress, Antioxidant Status, and Lipid Profile in Chronic Obstructive Pulmonary Disease Patients

    Directory of Open Access Journals (Sweden)

    Md. Ismail

    2015-01-01

    Full Text Available Background and Objective. Oxidative stress is intimately associated with many diseases, including chronic obstructive pulmonary disease (COPD. Study objectives include a comparison of the oxidative stress, antioxidant status, and lipid profile between COPD patients and controls and evaluation of the effect of spirulina intervention on oxidative stress, antioxidant status, and lipid profile of COPD patients. Methods. 30 patients with COPD and 20 controls with no respiratory problems were selected. Global Initiative for Chronic Obstructive Lung Disease criteria were served as the basis of COPD diagnosis. The serum content of malondialdehyde (MDA, lipid hydroperoxide, glutathione (GSH, vitamin C, cholesterol, triglyceride (TG, and high density lipoprotein (HDL was measured. The activity of superoxide dismutase (SOD, catalase (CAT, and glutathione-s-transferase (GST was also measured. Two different doses, (500 × 2 mg and (500 × 4 mg spirulina, were given to two groups, each of which comprises 15 COPD patients. Results. All targeted blood parameters have significant difference (P=0.000 between COPD patients and controls except triglyceride (TG. Spirulina intake for 30 and 60 days at (500 × 2 mg dose has significantly reduced serum content of MDA, lipid hydroperoxide, and cholesterol (P=0.000 while increasing GSH, Vit C level (P=0.000, and the activity of SOD (P=0.000 and GST (P=0.038. At the same time, spirulina intake for 30 and 60 days at (500 × 4 mg dose has favorable significant effect (P=0.000 on all targeted blood parameters except for HDL (P=0.163.

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

    Science.gov (United States)

    Bahi, Amine

    2013-07-01

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

  10. Chronic stress decreases the expression of sympathetic markers in the pineal gland and increases plasma melatonin concentration in rats.

    Science.gov (United States)

    Dagnino-Subiabre, Alexies; Orellana, Juan A; Carmona-Fontaine, Carlos; Montiel, Juan; Díaz-Velíz, Gabriela; Serón-Ferré, María; Wyneken, Ursula; Concha, Miguel L; Aboitiz, Francisco

    2006-06-01

    Chronic stress affects brain areas involved in learning and emotional responses. Although most studies have concentrated on the effect of stress on limbic-related brain structures, in this study we investigated whether chronic stress might induce impairments in diencephalic structures associated with limbic components of the stress response. Specifically, we analyzed the effect of chronic immobilization stress on the expression of sympathetic markers in the rat epithalamic pineal gland by immunohistochemistry and western blot, whereas the plasma melatonin concentration was determined by radioimmunoassay. We found that chronic stress decreased the expression of three sympathetic markers in the pineal gland, tyrosine hydroxylase, the p75 neurotrophin receptor and alpha-tubulin, while the same treatment did not affect the expression of the non-specific sympathetic markers Erk1 and Erk2, and glyceraldehyde-3-phosphate dehydrogenase. Furthermore, these results were correlated with a significant increase in plasma melatonin concentration in stressed rats when compared with control animals. Our findings indicate that stress may impair pineal sympathetic inputs, leading to an abnormal melatonin release that may contribute to environmental maladaptation. In addition, we propose that the pineal gland is a target of glucocorticoid damage during stress.

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

    Science.gov (United States)

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

    2015-12-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

  13. Chronic stress, inflammation, and glucose regulation in U.S. Hispanics from the HCHS/SOL Sociocultural Ancillary Study.

    Science.gov (United States)

    McCurley, Jessica L; Mills, Paul J; Roesch, Scott C; Carnethon, Mercedes; Giacinto, Rebeca E; Isasi, Carmen R; Teng, Yanping; Sotres-Alvarez, Daniela; Llabre, Maria M; Penedo, Frank J; Schneiderman, Neil; Gallo, Linda C

    2015-08-01

    Diabetes prevalence is rising rapidly, and diabetes disproportionately affects Hispanics and other underserved groups. Chronic stress may contribute to diabetes risk, but few studies have examined this relationship in U.S. Hispanics. We examined associations of chronic stress with fasting glucose, glucose tolerance, and glycosylated hemoglobin (HbA1c) in Hispanics without diabetes, and also assessed indirect effects of stress through inflammation (CRP). Participants were 3,923 men and women, aged 18-74, without diabetes, from the four U.S. field centers (Bronx, NY; Chicago, IL; Miami, FL; San Diego, CA) of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Sociocultural Ancillary study. Participants completed a measure of chronic life stress and a physical exam with oral glucose tolerance test. In a multivariate regression analysis with adjustment for demographic and health covariates, higher chronic stress was related to higher fasting glucose (standardized regression coefficient: β = .09, p effect of stress through inflammation. Findings suggest that higher chronic stress is associated with poorer glucose regulation in Hispanics, prior to the onset of a clinical diabetes diagnosis.

  14. The cost of chronic stress in childhood: understanding and applying the concept of allostatic load.

    Science.gov (United States)

    Katz, Debra A; Sprang, Ginny; Cooke, Circe

    2012-09-01

    This article explores the concept of allostatic load and its utility as an integrative framework for thinking about the impact of chronic stress on children and adolescents. Allostatic load refers to the failure or exhaustion of normal physiologic processes that occurs in response to severe, frequent, or chronic stressors. This persistent physiologic dysregulation may lead to secondary health problems such as immunosuppression, obesity, atherosclerosis, and hypertension. Allostatic load can be measured and followed as a composite index of a group of physiologic parameters which fall outside of a normal range. Although research regarding allostatic load in children is limited, this article explores relevant studies and identifies ways in which the concept of allostatic load can be used to broaden approaches to assessment, case formulation, and treatment in children. The concept of allostatic load may be of particular interest to psychodynamic psychiatrists in recognizing the ways in which chronic stress and adverse childhood experiences lead not only to negative psychological sequelae but also to long-term health consequences including the possibility of premature death. It underscores the importance of monitoring patients' physical as well as psychological health and thinking about the complex interrelations between the two.

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

    Directory of Open Access Journals (Sweden)

    Torres R.L.

    2004-01-01

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

  16. New clinical guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients.

    Science.gov (United States)

    Onoda, Noritaka; Fukagawa, Masafumi; Tominaga, Yoshihiro; Kitaoka, Masafumi; Akizawa, Tadao; Koiwa, Fumihiko; Kakuta, Takatoshi; Kurokawa, Kiyoshi

    2008-08-01

    In 2000, the Japanese Society for Parathyroid Intervention issued the 'Guidelines for percutaneous ethanol injection therapy of the parathyroid glands in chronic dialysis patients'. Since then, the concept of 'selective PEIT' has been well accepted and the number of patients treated by this method in Japan has increased. Recently, it has been reported that the effect of PEIT differs depending on the degree of nodular hyperplasia. Several new drugs have become available since 2000, and active vitamin D and its analogue have also been used for direct injection into the parathyroids. We present the new 'Guidelines for selective direct injection therapy of the parathyroid glands in chronic dialysis patients', a revised version of the 2000 Guidelines. We believe that these new guidelines are useful for selecting direct injection therapy in patients with advanced secondary hyperparathyroidism.

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

    Directory of Open Access Journals (Sweden)

    Daliao Xiao

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

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

    Science.gov (United States)

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

    2013-11-12

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

  19. Chronic Psychosocial Stress and Negative Feedback Inhibition: Enhanced Hippocampal Glucocorticoid Signaling despite Lower Cytoplasmic GR Expression.

    Science.gov (United States)

    Füchsl, Andrea M; Reber, Stefan O

    2016-01-01

    Chronic subordinate colony housing (CSC), a pre-clinically validated mouse model for chronic psychosocial stress, results in increased basal and acute stress-induced plasma adrenocorticotropic hormone (ACTH) levels. We assessed CSC effects on hippocampal glucocorticoid (GC) receptor (GR), mineralocorticoid receptor (MR), and FK506 binding protein (FKBP51) expression, acute heterotypic stressor-induced GR translocation, as well as GC effects on gene expression and cell viability in isolated hippocampal cells. CSC mice showed decreased GR mRNA and cytoplasmic protein levels compared with single-housed control (SHC) mice. Basal and acute stress-induced nuclear GR protein expression were comparable between CSC and SHC mice, as were MR and FKBP51 mRNA and/or cytoplasmic protein levels. In vitro the effect of corticosterone (CORT) on hippocampal cell viability and gene transcription was more pronounced in CSC versus SHC mice. In summary, CSC mice show an, if at all, increased hippocampal GC signaling capacity despite lower cytoplasmic GR protein expression, making negative feedback deficits in the hippocampus unlikely to contribute to the increased ACTH drive following CSC.

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

    Science.gov (United States)

    Prakash, Chandra; Kumar, Vijay

    2016-09-01

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

  1. Chromatin remodeling regulates catalase expression during cancer cells adaptation to chronic oxidative stress.

    Science.gov (United States)

    Glorieux, Christophe; Sandoval, Juan Marcelo; Fattaccioli, Antoine; Dejeans, Nicolas; Garbe, James C; Dieu, Marc; Verrax, Julien; Renard, Patricia; Huang, Peng; Calderon, Pedro Buc

    2016-10-01

    Regulation of ROS metabolism plays a major role in cellular adaptation to oxidative stress in cancer cells, but the molecular mechanism that regulates catalase, a key antioxidant enzyme responsible for conversion of hydrogen peroxide to water and oxygen, remains to be elucidated. Therefore, we investigated the transcriptional regulatory mechanism controlling catalase expression in three human mammary cell lines: the normal mammary epithelial 250MK primary cells, the breast adenocarcinoma MCF-7 cells and an experimental model of MCF-7 cells resistant against oxidative stress resulting from chronic exposure to H2O2 (Resox), in which catalase was overexpressed. Here we identify a novel promoter region responsible for the regulation of catalase expression at -1518/-1226 locus and the key molecules that interact with this promoter and affect catalase transcription. We show that the AP-1 family member JunB and retinoic acid receptor alpha (RARα) mediate catalase transcriptional activation and repression, respectively, by controlling chromatin remodeling through a histone deacetylases-dependent mechanism. This regulatory mechanism plays an important role in redox adaptation to chronic exposure to H2O2 in breast cancer cells. Our study suggests that cancer adaptation to oxidative stress may be regulated by transcriptional factors through chromatin remodeling, and reveals a potential new mechanism to target cancer cells.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    independent Caucasian samples (242 U.S. women and men; 466 Danish men) testing the hypothesis that chronic family stress also moderates the association between rs157580 and triglyceride levels. The interaction of rs157580 and family stress in predicting triglyceride levels was statistically significant...

  4. Brief RU 38486 Treatment Normalizes the Effects of Chronic Stress on Calcium Currents in Rat Hippocampal CA1 Neurons.

    NARCIS (Netherlands)

    Karst, H.; Joëls, M.

    2007-01-01

    Chronic stress alters many properties in rat brain, like serotonin responsiveness and dendritic morphology. In the present study, we examined (i) whether unpredictable stress during 21 days affects calcium (Ca) currents of CA1 pyramidal neurons recorded on day 22; and (ii) if so, whether this change

  5. Effect of chronic stress and mifepristone treatment on voltage-dependent Ca2+ currents in rat hippocampal dentate gyrus.

    NARCIS (Netherlands)

    van Gemert, N.G.; Joëls, M.

    2006-01-01

    Chronic unpredictable stress affects many properties in rat brain. In the dentate gyrus, among other things, increased mRNA expression of the Ca2+ channel alpha1C subunit has been found after 21 days of unpredictable stress in combination with acute corticosterone application (100 nM). In the presen

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

    Science.gov (United States)

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

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

    Science.gov (United States)

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

    2013-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Chih-Chien Sung

    2013-01-01

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

  9. Targeting the transcription factor Nrf2 to ameliorate oxidative stress and inflammation in chronic kidney disease.

    Science.gov (United States)

    Ruiz, Stacey; Pergola, Pablo E; Zager, Richard A; Vaziri, Nosratola D

    2013-06-01

    Oxidative stress and inflammation are mediators in the development and progression of chronic kidney disease (CKD) and its complications, and they are inseparably linked as each begets and amplifies the other. CKD-associated oxidative stress is due to increased production of reactive oxygen species (ROS) and diminished antioxidant capacity. The latter is largely caused by impaired activation of Nrf2, the transcription factor that regulates genes encoding antioxidant and detoxifying molecules. Protective effects of Nrf2 are evidenced by amelioration of oxidative stress, inflammation, and kidney disease in response to natural Nrf2 activators in animal models, while Nrf2 deletion amplifies these pathogenic pathways and leads to autoimmune nephritis. Given the role of impaired Nrf2 activity in CKD-induced oxidative stress and inflammation, interventions aimed at restoring Nrf2 may be effective in retarding CKD progression. Clinical trials of the potent Nrf2 activator bardoxolone methyl showed significant improvement in renal function in CKD patients with type 2 diabetes. However, due to unforeseen complications the BEACON trial, which was designed to investigate the effect of this drug on time to end-stage renal disease or cardiovascular death in patients with advanced CKD, was prematurely terminated. This article provides an overview of the role of impaired Nrf2 activity in the pathogenesis of CKD-associated oxidative stress and inflammation and the potential utility of targeting Nrf2 in the treatment of CKD.

  10. Effects of delta9-tetrahydrocannabinol on reward and anxiety in rats exposed to chronic unpredictable stress.

    Science.gov (United States)

    Fokos, S; Panagis, G

    2010-05-01

    Although cannabis derivatives produce clear subjective motivational responses in humans leading to drug-seeking behaviour, the reinforcing attributes of these subjective effects are difficult to define in experimental animals. The aim of this study was to examine how exposure to chronic unpredictable stress (CUS) will affect reward function and anxiety after acute administration of Delta(9)-tetrahydrocannabinol (Delta(9)-THC) in rats. Male rats were exposed to either 10 days of CUS or no stressor. Alterations in brain reward function were assessed with the intracranial self-stimulation (ICSS) paradigm, and anxiety responses were measured with the elevated plus maze. CUS did not affect baseline brain stimulation reward thresholds. Delta(9)-THC did not exhibit reinforcing actions in the ICSS paradigm neither in nonstressed nor in stressed animals. More importantly, in nonstressed animals, both the low and the high dose of Delta(9)-THC exerted anxiolytic-like effects. In stressed animals, however, only the high dose of THC induced an anxiolytic-like response, whereas the low dose induced anxiogenic effects. The present results provide clear evidence for an anxiolytic effect of Delta(9)-THC both in stressed and in nonstressed animals, and indicate that environmental conditions, such as stressful experiences, do not alter the behavioural effects of Delta( 9)-THC in the ICSS paradigm.

  11. Endoplasmic reticulum stress inhibition attenuates hypertensive chronic kidney disease through reduction in proteinuria

    Science.gov (United States)

    Mohammed-Ali, Zahraa; Lu, Chao; Marway, Mandeep K.; Carlisle, Rachel E.; Ask, Kjetil; Lukic, Dusan; Krepinsky, Joan C.; Dickhout, Jeffrey G.

    2017-01-01

    Endoplasmic reticulum (ER) stress is implicated in chronic kidney disease (CKD) development in patients and in animal models. Here we show that ER stress inhibition through 4-phenylbutyric acid (4-PBA) administration decreases blood pressure, albuminuria, and tubular casts in an angiotensin II/deoxycorticosterone acetate/salt murine model of CKD. Lower albuminuria in 4-PBA-treated mice was associated with higher levels of cubilin protein in renal tissue membrane fractions. 4-PBA decreased renal interstitial fibrosis, renal CD3+ T-cell and macrophage infiltration, mRNA expression of TGFβ1, Wnt signaling molecules, and ER stress-induced pro-inflammatory genes. CHOP deficient mice that underwent this model of CKD developed hypertension comparable to wild type mice, but had less albuminuria and tubular casts. CHOP deficiency resulted in higher nephrin levels and decreased glomerulosclerosis compared to wild type mice; this effect was accompanied by lower macrophage infiltration and fibrosis. Our findings portray ER stress inhibition as a means to alleviate hypertensive CKD by preserving glomerular barrier integrity and tubular function. These results demonstrate ER stress modulation as a novel target for preserving renal function in hypertensive CKD. PMID:28148966

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Rachel Ivy Anderson

    2016-02-01

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

  14. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

    Directory of Open Access Journals (Sweden)

    Yun Wang

    2017-01-01

    Full Text Available Methamphetamine (MA leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS. The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA, and MA plus TBHQ-treated group (MA + TBHQ. Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity.

  15. TBHQ Alleviated Endoplasmic Reticulum Stress-Apoptosis and Oxidative Stress by PERK-Nrf2 Crosstalk in Methamphetamine-Induced Chronic Pulmonary Toxicity

    Science.gov (United States)

    Gu, Yu-Han; Liu, Ming; Bai, Yang; Liang, Li-Ye; Wang, Huai-Liang

    2017-01-01

    Methamphetamine (MA) leads to cardiac and pulmonary toxicity expressed as increases in inflammatory responses and oxidative stress. However, some interactions may exist between oxidative stress and endoplasmic reticulum stress (ERS). The current study is designed to investigate if both oxidative stress and ERS are involved in MA-induced chronic pulmonary toxicity and if antioxidant tertiary butylhydroquinone (TBHQ) alleviated ERS-apoptosis and oxidative stress by PERK-Nrf2 crosstalk. In this study, the rats were randomly divided into control group, MA-treated group (MA), and MA plus TBHQ-treated group (MA + TBHQ). Chronic exposure to MA resulted in slower growth of weight and pulmonary toxicity of the rats by increasing the pulmonary arterial pressure, promoting the hypertrophy of right ventricle and the remodeling of pulmonary arteries. MA inhibited the Nrf2-mediated antioxidative stress by downregulation of Nrf2, GCS, and HO-1 and upregulation of SOD2. MA increased GRP78 to induce ERS. Overexpression and phosphorylation of PERK rapidly phosphorylated eIF2α, increased ATF4, CHOP, bax, caspase 3, and caspase 12, and decreased bcl-2. These changes can be reversed by antioxidant TBHQ through upregulating expression of Nrf2. The above results indicated that TBHQ can alleviate MA-induced oxidative stress which can accelerate ERS to initiate PERK-dependent apoptosis and that PERK/Nrf2 is likely to be the key crosstalk between oxidative stress and ERS in MA-induced chronic pulmonary toxicity. PMID:28303170

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

    Science.gov (United States)

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

    2014-02-01

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

  17. Stress within a restricted time window selectively affects the persistence of long-term memory.

    Directory of Open Access Journals (Sweden)

    Chang Yang

    Full Text Available The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM formation (tested 24 h later, but the effects of stress on the persistence of LTM (tested at least 1 week later are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system.

  18. Blood micronutrient, oxidative stress, and viral load in patients with chronic hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Wang-Sheng Ko; Chih-Hung Guo; Maw-Sheng Yeh; Li-Yun Lin; Guoo-Shyng W.Hsu; Pei-Chung Chen; Mei-Ching Luo; Chia-Yeh Lin

    2005-01-01

    AIM: To assess the extent of micronutrient and oxidative stress in blood and to examine their linkages with viral loads in chronic hepatitis C patients.METHODS: Hepatitis C virus (HCV)-RNA levels were quantified in the serum from 37 previously untreated patients with chronic hepatitis C. The plasma and erythrocyte micronutrients (zinc, selenium, copper, and iron) were estimated, and malondialdehyde (MDA)contents were determined as a marker to detect oxidative stress. Antioxidant enzymes, superoxide dismutase (SOD),glutathione peroxidase (GPX) and glutathione reductase (GR) activities in blood were also measured. The control group contained 31 healthy volunteers.RESULTS: The contents of zinc (Zn), and selenium (Se)in plasma and erythrocytes were significantly lower in hepatitis C patients than in the controls. On the contrary,copper (Cu) levels were significantly higher. Furthermore,plasma and erythrocyte MDA levels, and the SOD and GR activities in erythrocytes significantly increased in hepatitis C patients compared to the controls. However, the plasma GPX activity in patients was markedly lower. Plasma Se (r= -0.730, P<0.05), Cu (r = 0.635), and GPX (r = -0.675)demonstrated correlations with HCV-RNA loads. Significant correlation coefficients were also observed between HCV-RNA levels and erythrocyte Zn (r = -0.403), Se (r = -0.544), Cu (r = 0.701) and MDA (r = 0.629) and GR (r = 0.441).CONCLUSION: The levels of Zn, Se, Cu, and oxidative stress (MDA), as well as related anti-oxidative enzymes (GR and GPX) in blood have important impact on the viral factors in chronic hepatitis C. The distribution of these parameters might be significant biomarkers for HCV.

  19. 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.

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

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    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....

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

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    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...

  2. Telephone monitoring and support for veterans with chronic posttraumatic stress disorder: a pilot study.

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    Rosen, Craig S; DiLandro, Caryn; Corwin, Kim N; Drescher, Kent D; Cooney, Jean H; Gusman, Fred

    2006-10-01

    Dropout from outpatient mental health treatment may contribute to high rates of relapse and rehospitalization among veterans with chronic posttraumatic stress disorder (PTSD). In a quasi-experimental cohort study, 87 male and 17 female veterans discharging from residential PTSD treatment received either standard referral to outpatient care (N = 77) or standard referrals supplemented by biweekly telephone calls (N = 27). Telephone monitoring and support was feasible and acceptable to 85% of clients. Compared to prior patient cohorts, clients receiving telephone support were twice as likely (88% vs. 43%) to complete an outpatient visit within 1 month of discharge and reported higher satisfaction with care.

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

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    Bruder-Nascimento, Thiago; Campos, Dijon Henrique Salome

    2015-01-23

    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)Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi

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

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    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...

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

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    José Pedraza-Chaverri

    2016-01-01

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

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

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    Palić, Sabina; Elklit, Ask

    2014-02-01

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

  7. 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.

  8. Comparison of miRNA expression profiles in pituitary-adrenal axis between Beagle and Chinese Field dogs after chronic stress exposure.

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    Luo, Wei; Fang, Meixia; Xu, Haiping; Xing, Huijie; Fu, Jiangnan; Nie, Qinghua

    2016-01-01

    MicoRNAs (miRNAs), usually as gene regulators, participate in various biological processes, including stress responses. The hypothalamus-pituitary-adrenal axis (HPA axis) is an important pathway in regulating stress response. Although the mechanism that HPA axis regulates stress response has been basically revealed, the knowledge that miRNAs regulate stress response within HPA axis, still remains poor. The object of this study was to investigate the miRNAs in the pituitary and adrenal cortex that regulate chronic stress response with high-throughput sequencing. The pituitary and adrenal cortex of beagles and Chinese Field dogs (CFD) from a stress exposure group (including beagle pituitary 1 (BP1), CFD pituitary 1 (CFDP1), beagle adrenal cortex 1 (BAC1), CFD adrenal cortex 1 (CFDAC1)) and a control group (including beagle pituitary 2 (BP2), CFD pituitary 2 (CFDP2), beagle adrenal cortex 2 (BAC2), CFD adrenal cortex 2 (CFDAC2)), were selected for miRNA-seq comparisons. Comparisons, that were made in pituitary (including BP1 vs. BP2, CFDP1 vs. CFDP2, BP1 vs. CFDP1 and BP2 vs. CFDP2) and adrenal cortex (including BAC1 vs. BAC2, CFDAC1 vs. CFDAC2, BAC1 vs. CFDAC1 and BAC2 vs. CFDAC2), showed that a total of 39 and 18 common differentially expressed miRNAs (DE-miRNAs) (Total read counts > 1,000, Fold change > 2 & p-value 2 & p-value < 0.05) from those target genes in pituitary and adrenal cortex were obtained separately, in combination with our previous corresponding transcriptome study. Meanwhile, in line with that miRNAs usually negatively regulated their target genes and the dual luciferase reporter assay, we finally identified cfa-miR-205 might play an important role by upregulating MMD in pituitary and hippocampus, thus enhancing the immune response, under chronic stress exposure. Our results shed light on the miRNA expression profiles in the pituitary and adrenal cortex with and without chronic stress exposure, and provide a new insight into miR-205 with its

  9. Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation.

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    Coder, Brandon D; Wang, Hongjun; Ruan, Linhui; Su, Dong-Ming

    2015-06-15

    Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non-lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).

  10. 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.

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

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    Maryam Radahmadi

    2013-01-01

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

  12. Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice.

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    Yang, Chun; Fujita, Yuko; Ren, Qian; Ma, Min; Dong, Chao; Hashimoto, Kenji

    2017-04-03

    Accumulating evidence suggests that abnormalities in the composition of the gut microbiota may play a role in the pathogenesis of depression. Although approximately 30% mice are resilient to chronic social defeat stress (CSDS), the role of gut microbiota in this stress resilience is unknown. In this study, male C57BL/6 mice were exposed to a different CD1 aggressor mouse for 10 min on 10 consecutive days. A social interaction test was applied to distinguish between resilient and susceptible mice. Using 16S rRNA analysis, we examined the composition of gut microbiota in feces from control, resilient, and susceptible mice. The marked appearance of Bifidobacterium was detected in the resilient mice, whereas in the control and susceptible mice, Bifidobacterium were below the detection limit. Oral intake of Bifidobacterium significantly increased the number of resilient mice after CSDS compared with vehicle-treated mice. These findings suggest that Bifidobacterium may confer resilience to CSDS. Therefore, supplementation of Bifidobacterium may prevent the onset of depression from stress in humans. In addition, supplementation of Bifidobacterium may prevent or minimize relapse from remission induced by inflammation and/or stress in depressed patients.

  13. Bifidobacterium in the gut microbiota confer resilience to chronic social defeat stress in mice

    Science.gov (United States)

    Yang, Chun; Fujita, Yuko; Ren, Qian; Ma, Min; Dong, Chao; Hashimoto, Kenji

    2017-01-01

    Accumulating evidence suggests that abnormalities in the composition of the gut microbiota may play a role in the pathogenesis of depression. Although approximately 30% mice are resilient to chronic social defeat stress (CSDS), the role of gut microbiota in this stress resilience is unknown. In this study, male C57BL/6 mice were exposed to a different CD1 aggressor mouse for 10 min on 10 consecutive days. A social interaction test was applied to distinguish between resilient and susceptible mice. Using 16S rRNA analysis, we examined the composition of gut microbiota in feces from control, resilient, and susceptible mice. The marked appearance of Bifidobacterium was detected in the resilient mice, whereas in the control and susceptible mice, Bifidobacterium were below the detection limit. Oral intake of Bifidobacterium significantly increased the number of resilient mice after CSDS compared with vehicle-treated mice. These findings suggest that Bifidobacterium may confer resilience to CSDS. Therefore, supplementation of Bifidobacterium may prevent the onset of depression from stress in humans. In addition, supplementation of Bifidobacterium may prevent or minimize relapse from remission induced by inflammation and/or stress in depressed patients. PMID:28368029

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

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    Farideh Zafari Zangeneh

    2009-12-01

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

  15. Reduced tonic inhibition in the dentate gyrus contributes to chronic stress-induced impairments in learning and memory.

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    Lee, Vallent; MacKenzie, Georgina; Hooper, Andrew; Maguire, Jamie

    2016-10-01

    It is well established that stress impacts the underlying processes of learning and memory. The effects of stress on memory are thought to involve, at least in part, effects on the hippocampus, which is particularly vulnerable to stress. Chronic stress induces hippocampal alterations, including but not limited to dendritic atrophy and decreased neurogenesis, which are thought to contribute to chronic stress-induced hippocampal dysfunction and deficits in learning and memory. Changes in synaptic transmission, including changes in GABAergic inhibition, have been documented following chronic stress. Recently, our laboratory demonstrated shifts in EGABA in CA1 pyramidal neurons following chronic stress, compromising GABAergic transmission and increasing excitability of these neurons. Interestingly, here we demonstrate that these alterations are unique to CA1 pyramidal neurons, since we do not observe shifts in EGABA following chronic stress in dentate gyrus granule cells. Following chronic stress, there is a decrease in the expression of the GABAA receptor (GABAA R) δ subunit and tonic GABAergic inhibition in dentate gyrus granule cells, whereas there is an increase in the phasic component of GABAergic inhibition, evident by an increase in the peak amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs). Given the numerous changes observed in the hippocampus following stress, it is difficult to pinpoint the pertinent contributing pathophysiological factors. Here we directly assess the impact of a reduction in tonic GABAergic inhibition of dentate gyrus granule cells on learning and memory using a mouse model with a decrease in GABAA R δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAA R δ subunit expression and function in dentate gyrus granule cells is sufficient to induce deficits in learning and memory. Collectively, these findings suggest that the reduction in GABAA R δ subunit-mediated tonic inhibition

  16. The Alterations of IL-1Beta, IL-6, and TGF-Beta Levels in Hippocampal CA3 Region of Chronic Restraint Stress Rats after Electroacupuncture (EA Pretreatment

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    Tianwei Guo

    2014-01-01

    Full Text Available Immunological reactions induced by proinflammatory cytokines have been involved in the pathogenesis of depressive disorders. Recent studies showed that Electroacupuncture (EA was able to reduce depressive symptoms; however, the underlying mechanism and its potential targets remain unknown. In the present study, we used a 21-day chronic restraint stress rats as a model to investigate how EA could alleviate depression. Open field test was carried out to evaluate the depressive symptoms at selected time points. At the end of study, immunohistochemistry (IHC was performed to detect the expressions of IL-1beta, IL-6, and TGF-beta in hippocampal CA3 region. We found that chronic restraint stress significantly decreased behavioral activities, whereas EA stimulation at points Baihui (GV 20 and Yintang (GV 29 showed protective effect during the test period. In addition, the IL-1beta, IL-6, and TGF-beta increased in rats exposed to chronic restraint stress, while EA downregulated the levels of IL-1beta and IL-6. These findings implied that EA pretreatment could alleviate depression through modulating IL-1beta and IL-6 expression levels in hippocampal CA3 region.

  17. The Alterations of IL-1Beta, IL-6, and TGF-Beta Levels in Hippocampal CA3 Region of Chronic Restraint Stress Rats after Electroacupuncture (EA) Pretreatment.

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    Guo, Tianwei; Guo, Zhuo; Yang, Xinjing; Sun, Lan; Wang, Sihan; Yingge, A; He, Xiaotian; Ya, Tu

    2014-01-01

    Immunological reactions induced by proinflammatory cytokines have been involved in the pathogenesis of depressive disorders. Recent studies showed that Electroacupuncture (EA) was able to reduce depressive symptoms; however, the underlying mechanism and its potential targets remain unknown. In the present study, we used a 21-day chronic restraint stress rats as a model to investigate how EA could alleviate depression. Open field test was carried out to evaluate the depressive symptoms at selected time points. At the end of study, immunohistochemistry (IHC) was performed to detect the expressions of IL-1beta, IL-6, and TGF-beta in hippocampal CA3 region. We found that chronic restraint stress significantly decreased behavioral activities, whereas EA stimulation at points Baihui (GV 20) and Yintang (GV 29) showed protective effect during the test period. In addition, the IL-1beta, IL-6, and TGF-beta increased in rats exposed to chronic restraint stress, while EA downregulated the levels of IL-1beta and IL-6. These findings implied that EA pretreatment could alleviate depression through modulating IL-1beta and IL-6 expression levels in hippocampal CA3 region.

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

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    Bosma-den Boer Margarethe M

    2012-04-01

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

  19. 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

  20. Changes of mRNA expression of enkephalin and prodynorphin in hippocampus of rats with chronic immobilization stress

    Institute of Scientific and Technical Information of China (English)

    Jia-Xu Chen; Wei Li; Xin Zhao; Jian-Xin Yang; Hong-Yan Xu; Zhu-Feng Wang; Guang-Xin Yue

    2004-01-01

    AIM: To observe the changes of enkephalin mRNA and prodynorphin mRNA in hippocampus of rats induced by chronic immobilization stress.METHODS: Thirty rats were randomly divided into three groups of 10 each: the normal control group (group A),the group induced by chronic immobilization stress for 7 d (group B) and the group induced by chronic immobilization stress for 21 d (group C). The changes of the enkephalin mRNA and prodynorphin mRNA in the rat hippocampus were detected by reverse transcription-polymerase chain reaction (RT-PCR).RESULTS: Expression levels of enkephalin mRNA and prodynorphin mRNA in rat hippocampus were significantly increased under chronic immobilization stress, and the expression of prodynorphin mRNA in the rat hippocampus in group C was remarkably higher than that in group B (0.624±0.026; n = 5; P<0.01).CONCLUSION: The increased enkephalin mRNA and prodynorphin mRNA gene expressions in rat hippocampus were involved in chronic stress.

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

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

    2016-04-13

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

  2. 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

  3. Solcoseryl in prevention of stress-induced gastric lesions and healing of chronic ulcers.

    Science.gov (United States)

    Konturek, S J; Drozdowicz, D; Pytko-Polonczyk, J; Brzozowski, T; Bielański, W

    1991-03-01

    Solcoseryl, a deproteinized extract of calf blood, protects the gastric mucosa against various topical irritants and enhances the healing of chronic gastric ulcerations but the mechanisms of these effects have been little studied. This study was designed to elucidate the active principle in Solcoseryl and to determine the role of prostaglandins (PG) and polyamines in the antiulcer properties of this agent. Using both, the radioimmunoassay and radioreceptor assay, EGF-like material was detected in Solcoseryl preparation. Solcoseryl given s.c. prevented the formation of stress-induced gastric lesions and this was accompanied by an increase in the generation of PGE2 in the gastric mucosa. Similar effects were obtained with EGF. Pretreatment with indomethacin, to suppress mucosal generation of prostaglandins (PG), greatly augmented stress-induced gastric ulcerations and antagonized the protection exerted by both Solcoseryl and EGF. Solcoseryl, like EGF, enhanced the healing of chronic gastro-duodenal ulcerations. This effect was abolished by the pretreatment with difluoromethylornithine, an inhibitor of ornithine decarboxylase, the key enzyme in the biosynthesis of polyamines. The healing effects of Solcoseryl and EGF was also reduced by prednisolone which decreased the angiogenesis in the granulation tissue in the ulcer area. These results indicate that Solcoseryl 1. contains EGF-like material, 2. displays the protective and ulcer healing effects similar to those of EGF and involving both PG and polyamines and 3. acts via similar mechanism as does EGF.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  5. Effect of elective surgery on subjective health in veterans with chronic posttraumatic stress disorder.

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    Wofford, Ken; Hertzberg, Michael; Silva, Susan; Vacchiano, Charles

    2014-08-01

    Posttraumatic stress disorder (PTSD) is common, is often chronic, and has been associated with greater risk of postoperative mortality in veterans. The purpose of this study was to determine if elective outpatient surgery had a persistent effect on the physical or mental health of veterans with chronic PTSD. A longitudinal, quasi-experimental study was conducted that followed up 60 veterans with chronic PTSD over 12 weeks. Self-reported physical and mental health, depressive symptom severity, and posttraumatic symptom severity were measured in 29 veterans undergoing outpatient elective surgery and 31 veterans not having elective surgery (controls). Data collection was performed at baseline and repeated 1, 4, and 12 weeks after surgery or enrollment. At baseline, both surgical and control subjects reported poor physical and mental subjective health status. After surgery, surgical group subjects reported mean age- and gender-adjusted reductions of 3.9 points on the Physical Component Summary score and 2.9 points on the Mental Component Summary score of the Veterans Rand 36-item Health Survey, which resolved by 4 weeks after surgery. These findings suggest that veterans with PTSD were at greater risk of mortality because of poor baseline health, but did not demonstrate persistent decline in health following common elective surgical procedures.

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

    Institute of Scientific and Technical Information of China (English)

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

    2013-01-01

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

  7. Chronic-Alcohol-Abuse-Induced Oxidative Stress in the Development of Acute Respiratory Distress Syndrome

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    Yan Liang

    2012-01-01

    Full Text Available Chronic alcohol ingestion increases the risk of developing acute respiratory distress syndrome (ARDS, a severe form of acute lung injury, characterized by alveolar epithelial and endothelial barrier disruption and intense inflammation. Alcohol abuse is also associated with a higher incidence of sepsis or pneumonia resulting in a higher rate of admittance to intensive care, longer inpatient stays, higher healthcare costs, and a 2–4 times greater mortality rate. Chronic alcohol ingestion induced severe oxidative stress associated with increased ROS generation, depletion of the critical antioxidant glutathione (GSH, and oxidation of the thiol/disulfide redox potential in the alveolar epithelial lining fluid and exhaled breath condensate. Across intracellular and extracellular GSH pools in alveolar type II cells and alveolar macrophages, chronic alcohol ingestion consistently induced a 40–60 mV oxidation of GSH/GSSG suggesting that the redox potentials of different alveolar GSH pools are in equilibrium. Alcohol-induced GSH depletion or oxidation was associated with impaired functions of alveolar type II cells and alveolar macrophages but could be reversed by restoring GSH pools in the alveolar lining fluid. The aims of this paper are to address the mechanisms for alcohol-induced GSH depletion and oxidation and the subsequent effects in alveolar barrier integrity, modulation of the immune response, and apoptosis.

  8. Increased glycation of hemoglobin in chronic renal failure: [corrected] potential role of oxidative stress.

    Science.gov (United States)

    Selvaraj, Nambiar; Bobby, Zachariah; Sridhar, Magadi Gopalakrishna

    2008-04-01

    Among the various mechanisms proposed, the process of non-enzymatic glycation of proteins is believed to play an important role in the pathogenesis of chronic complications associated with renal failure. The two traditional factors found to modulate the early glycation of proteins are the prevailing concentration of glucose and half life of the protein. Among the various proteins that are known to undergo nonenzymatic glycation in vivo, hemoglobin has been the most thoroughly investigated. Determination of glycated hemoglobin in diabetic patients is currently acknowledged as the most reliable indicator for assessment of retrospective glycemic control and the planning of clinical management. The clinical utility of glycated hemoglobin measurements, however, in renal failure is controversial, given the numerous earlier studies showing no correlation between glycated hemoglobin and other indicators of blood glucose control in uremic subjects. With few exceptions, previous studies have suggested that the concentration of glycated hemoglobin was increased in uremic patients. There is documented evidence that increased glycated hemoglobin levels are found in certain non-diabetic states. So it stands to reason that hyperglycemia, although clearly being the culprit in diabetes, does not provide the complete answer to the etiology of increased early glycated products in non-diabetic conditions including chronic renal failure. This article reviews available evidence supporting increased glycation of hemoglobin in patients with chronic renal failure. Potential mechanisms for this increase are examined with special emphasis on the potential role of oxidative stress.

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

    Science.gov (United States)

    Kim, D-M; Leem, Y-H

    2016-06-02

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

  10. 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.

  11. Effects of repetitive stress during the acute phase of Trypanosoma cruzi infection on chronic Chagas' disease in rats.

    Science.gov (United States)

    Caetano, Leony Cristina; Brazão, Vânia; Filipin, Marina Del Vecchio; Santello, Fabricia Helena; Caetano, Luana Naiara; Toldo, Miriam Paula Alonso; Caldeira, Jerri C; do Prado, José Clóvis

    2009-03-01

    The effect of repetitive stress during acute infection with Trypanosoma cruzi (T. cruzi) on the chronic phase of ensuing Chagas' disease was the focus of this investigation. The aim of this study was to evaluate in Wistar rats the influence of repetitive stress during the acute phase of infection (7 days) with the Y strain of T. cruzi on the chronic phase of the infection (at 180 days). Exposure to ether vapor for 1 min twice a day was used as a stressor. Repetitive stress enhanced the number of circulating parasites and cardiac tissue disorganization, from a moderate to a severe diffuse mononuclear inflammatory process and the presence of amastigote burden in the cardiac fibers. Immunological parameters revealed that repetitive stress triggered a reduced concanavalin A induced splenocyte proliferation in vitro with major effects on the late chronic phase. Serum interleukin-12 concentration decreased in both stressed and infected rats in the early phase of infection although it was higher on 180 days post-infection. These results suggest that repetitive stress can markedly impair the host's immune system and enhance the pathological process during the chronic phase of Chagas' disease.

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

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    Georgia eBalsevich

    2015-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  14. Evaluation of association between psychological stress and serum cortisol levels in patients with chronic periodontitis - Estimation of relationship between psychological stress and periodontal status

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    Roshni Jaiswal

    2016-01-01

    Full Text Available Background: Stress classically describes a destructive notion that can have a bearing on one's physical and mental health. It may also add to an increased propensity to periodontal disease. Aim: To investigate the association between psychological stress and serum cortisol levels in patients with chronic periodontitis. Materials and Methods: Forty subjects were recruited from the outpatient department at the Department of Periodontics, from a college in Mangalore, divided into two groups, i.e., twenty as healthy controls and twenty were stressed subjects with chronic periodontitis. The clinical examination included the assessment of probing pocket depth, clinical attachment level and oral hygiene index-simplified. Serum cortisol levels were estimated biochemically using the enzyme-linked immunosorbent assay method and the estimation of psychological stress was done by a questionnaire. Results: Descriptive statistics such as mean and standard deviation was used to review the collected data. Independent sample t-test was used for comparison and correlation was evaluation using Pearson's correlation test. As per our observation, high serum cortisol levels and psychological stress are positively linked with chronic periodontitis establishing a risk profile showing a significant correlation (P < 0.05. Conclusion: Routine serum cortisol assessment may be a reasonable and a valuable investigative indicator to rule out stress in periodontitis patients as it should be considered as an imperative risk factor for periodontal disease.

  15. Chronic stress induces structural alterations in splenic lymphoid tissue that are associated with changes in corticosterone levels in wistar-kyoto rats.

    Science.gov (United States)

    Hernandez, María Eugenia; Martinez-Mota, Lucia; Salinas, Citlaltepetl; Marquez-Velasco, Ricardo; Hernandez-Chan, Nancy G; Morales-Montor, Jorge; Pérez-Tapia, Mayra; Streber, María L; Granados-Camacho, Ivonne; Becerril, Enrique; Javier, Baquera-Heredia; Pavón, Lenin

    2013-01-01

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

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

    Science.gov (United States)

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

    2010-10-01

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

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

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    Yihan Zhang

    2016-01-01

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

  18. 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.

  19. Macro-level modeling of the response of C. elegans reproduction to chronic heat stress.

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    Patrick D McMullen

    2012-01-01

    Full Text Available A major goal of systems biology is to understand how organism-level behavior arises from a myriad of molecular interactions. Often this involves complex sets of rules describing interactions among a large number of components. As an alternative, we have developed a simple, macro-level model to describe how chronic temperature stress affects reproduction in C. elegans. Our approach uses fundamental engineering principles, together with a limited set of experimentally derived facts, and provides quantitatively accurate predictions of performance under a range of physiologically relevant conditions. We generated detailed time-resolved experimental data to evaluate the ability of our model to describe the dynamics of C. elegans reproduction. We find considerable heterogeneity in responses of individual animals to heat stress, which can be understood as modulation of a few processes and may represent a strategy for coping with the ever-changing environment. Our experimental results and model provide quantitative insight into the breakdown of a robust biological system under stress and suggest, surprisingly, that the behavior of complex biological systems may be determined by a small number of key components.

  20. Chronic wound state exacerbated by oxidative stress in Pax6+/- aniridia-related keratopathy.

    Science.gov (United States)

    Ou, J; Walczysko, P; Kucerova, R; Rajnicek, A M; McCaig, C D; Zhao, M; Collinson, J M

    2008-08-01

    Heterozygosity for the transcription factor PAX6 causes eye disease in humans, characterized by corneal opacity. The molecular aetiology of such disease was investigated using a Pax6+/- mouse model. We found that the barrier function of uninjured Pax6+/- corneas was compromised and that Ca2+-PKC/PLC-ERK/p38 signalling pathways were abnormally activated, mimicking a 'wounded' epithelial state. Using proteomic analysis and direct assay for oxidized proteins, Pax6+/- corneas were found to be susceptible to oxidative stress and they exhibited a wound-healing delay which could be rescued by providing reducing agents such as glutathione. Pax6 protein was oxidized and excluded from the nucleus of stressed corneal epithelial cells, with concomitant loss of corneal epithelial markers and expression of fibroblast/myofibroblast markers. We suggest a chronic wound model for Pax6-related corneal diseases, in which oxidative stress underlies a positive feedback mechanism by depleting nuclear Pax6, delaying wound healing, and activating cell signalling pathways that lead to metaplasia of the corneal epithelium. The study mechanistically links a relatively minor dosage deficiency of a transcription factor with potentially catastrophic degenerative corneal disease.

  1. STRESS RELAXATION CHARACTERISTICS OF SELECTED COMMERCIALLY PRODUCED GLASSES

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    Chocholoušek J.

    2013-06-01

    Full Text Available This paper describes a quantitative method of stress relaxation measurement in prismatic glass samples during two different time-temperature regimes using the Sénarmont compensator. Four types of glass (Barium crystal glass, Eutal, Simax, and Container glass were subjected to observation in an assembled measuring device. Results will be used for parameterization of the Tool-Narayanaswamy-Mazurin model and consequently implemented in a finite element method code.

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

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    Lauren eChaby

    2013-07-01

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

  3. Exogenous Tryptophan Promotes Cutaneous Wound Healing of Chronically Stressed Mice through Inhibition of TNF-α and IDO Activation.

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    Luana Graziella Bandeira

    Full Text Available Stress prolongs the inflammatory response compromising the dermal reconstruction and wound closure. Acute stress-induced inflammation increases indoleamine 2, 3-dioxygenase-stimulated tryptophan catabolism. To investigate the role of indoleamine 2, 3-dioxygenase expression and tryptophan administration in adverse effects of stress on cutaneous wound healing, mice were submitted to chronic restraint stress and treated with tryptophan daily until euthanasia. Excisional lesions were created on each mouse and 5 or 7 days later, the lesions were analyzed. In addition, murine skin fibroblasts were exposed to elevated epinephrine levels plus tryptophan, and fibroblast activity was evaluated. Tryptophan administration reversed the reduction of the plasma tryptophan levels and the increase in the plasma normetanephrine levels induced by stress 5 and 7 days after wounding. Five days after wounding, stress-induced increase in the protein levels of tumor necrosis factor-α and indoleamine 2, 3-dioxygenase, and this was inhibited by tryptophan. Stress-induced increase in the lipid peroxidation and the amount of the neutrophils, macrophages and T cells number was reversed by tryptophan 5 days after wounding. Tryptophan administration inhibited the reduction of myofibroblast density, collagen deposition, re-epithelialization and wound contraction induced by stress 5 days after wounding. In dermal fibroblast culture, the tryptophan administration increased the cell migration and AKT phosphorylation in cells treated with high epinephrine levels. In conclusion, tryptophan-induced reduction of inflammatory response and indoleamine 2, 3-dioxygenase expression may have accelerated cutaneous wound healing of chronically stressed mice.

  4. Patient-specific finite element analysis of chronic contact stress exposure after intraarticular fracture of the tibial plafond.

    Science.gov (United States)

    Li, Wendy; Anderson, Donald D; Goldsworthy, Jane K; Marsh, J Lawrence; Brown, Thomas D

    2008-08-01

    The role of altered contact mechanics in the pathogenesis of posttraumatic osteoarthritis (PTOA) following intraarticular fracture remains poorly understood. One proposed etiology is that residual incongruities lead to altered joint contact stresses that, over time, predispose to PTOA. Prevailing joint contact stresses following surgical fracture reduction were quantified in this study using patient-specific contact finite element (FE) analysis. FE models were created for 11 ankle pairs from tibial plafond fracture patients. Both (reduced) fractured ankles and their intact contralaterals were modeled. A sequence of 13 loading instances was used to simulate the stance phase of gait. Contact stresses were summed across loadings in the simulation, weighted by resident time in the gait cycle. This chronic exposure measure, a metric of degeneration propensity, was then compared between intact and fractured ankle pairs. Intact ankles had lower peak contact stress exposures that were more uniform and centrally located. The series-average peak contact stress elevation for fractured ankles was 38% (p = 0.0015; peak elevation was 82%). Fractured ankles had less area with low contact stress exposure than intact ankles and a greater area with high exposure. Chronic contact stress overexposures (stresses exceeding a damage threshold) ranged from near zero to a high of 18 times the matched intact value. The patient-specific FE models represent substantial progress toward elucidating the relationship between altered contact stresses and the outcome of patients treated for intraarticular fractures.

  5. Wound-healing ability is conserved during periods of chronic stress and costly life history events in a wild-caught bird.

    Science.gov (United States)

    DuRant, S E; de Bruijn, R; Tran, M N; Romero, L M

    2016-04-01

    Chronic stress, potentially through the actions of corticosterone, is thought to directly impair the function of immune cells. However, chronic stress may also have an indirect effect by influencing allocation of energy, ultimately shifting resources away from the immune system. If so, the effects of chronic stress on immune responses may be greater during energetically-costly life history events. To test whether the effects of chronic stress on immune responses differ during expensive life history events we measured wound healing rate in molting and non-molting European starlings (Sturnus vulgaris) exposed to control or chronic stress conditions. To determine whether corticosterone correlated with wound healing rates before starting chronic stress, we measured baseline and stress-induced corticosterone and two estimates of corticosterone release and regulation, negative feedback (using dexamethasone injection), and maximal capacity of the adrenals to secrete corticosterone (using adrenocorticotropin hormone [ACTH] injection). After 8days of exposure to chronic stress, we wounded both control and chronically stressed birds and monitored healing daily. We monitored nighttime heart rate, which strongly correlates with energy expenditure, and body mass throughout the study. Measures of corticosterone did not differ with molt status. Contrary to work on lizards and small mammals, all birds, regardless of stress or molt status, fully-healed wounds at similar rates. Although chronic stress did not influence healing rates, individuals with low baseline corticosterone or strong negative feedback had faster healing rates than individuals with high baseline corticosterone or weak negative feedback. In addition, wound healing does appear to be linked to energy expenditure and body mass. Non-molting, chronically stressed birds decreased nighttime heart rate during healing, but this pattern did not exist in molting birds. Additionally, birds of heavier body mass at the start of

  6. 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

  7. The chronic psychosocial stress paradigm in male tree shrews: evaluation of a novel animal model for depressive disorders.

    Science.gov (United States)

    van Kampen, Marja; Kramer, Marian; Hiemke, Christoph; Flügge, Gabriele; Fuchs, Eberhard

    2002-02-01

    To improve our knowledge of the causal mechanisms of stress-related disorders such as depression, we need animal models that mirror the situation in patients. One promising model is the chronic psychosocial stress paradigm in male tree shrews, which is based on the territorial behaviour of these animals that can be used to establish naturally occurring challenging situations under experimental control in the laboratory. Co-existence of two males in visual and olfactory contact leads to a stable dominant-subordinate relationship, with subordinates showing distinct stress-induced behavioural and neuroendocrine alterations that are comparable to the symptoms observed during episodes of depression in patients such as constantly elevated circulating glucocorticoid hormones due to a chronic hyperactivity of the hypothalamic-pituitary-adrenal axis. To elucidate whether the chronic psychosocial stress model in tree shrews besides its "face validity" for depression also has "predictive validity", we treated subordinate tree shrews with the tricyclic antidepressant clomipramine and found a time-dependent restoration of both endocrine and behavioural parameters. In contrast, the anxiolytic diazepam was ineffective. Although the chronic psychosocial stress model in tree shrews requires further validation, it has sufficient face, predictive, and construct validity to become an interesting non-rodent model for research on the etiology and pathophysiology of depression.

  8. Does comorbid chronic pain affect posttraumatic stress disorder diagnosis and treatment? Outcomes of posttraumatic stress disorder screening in Department of Veterans Affairs primary care.

    Science.gov (United States)

    Outcalt, Samantha D; Hoen, Helena Maria; Yu, Zhangsheng; Franks, Tenesha Marie; Krebs, Erin E

    2016-01-01

    Because posttraumatic stress disorder (PTSD) is both prevalent and underrecognized, routine primary care-based screening for PTSD has been implemented across the Veterans Health Administration. PTSD is frequently complicated by the presence of comorbid chronic pain, and patients with both conditions have increased symptom severity and poorer prognosis. Our objective was to determine whether the presence of pain affects diagnosis and treatment of PTSD among Department of Veterans Affairs (VA) patients who have a positive PTSD screening test. This retrospective cohort study used clinical and administrative data from six Midwestern VA medical centers. We identified 4,244 VA primary care patients with a positive PTSD screen and compared outcomes for those with and without a coexisting pain diagnosis. Outcomes were three clinically appropriate responses to positive PTSD screening: (1) mental health visit, (2) PTSD diagnosis, and (3) new selective serotonin reuptake inhibitor (SSRI) prescription. We found that patients with coexisting pain had a lower rate of mental health visits than those without pain (hazard ratio: 0.889, 95% confidence interval: 0.821-0.962). There were no significant differences in the rate of PTSD diagnosis or new SSRI prescription between patients with and without coexisting pain.

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

    DEFF Research Database (Denmark)

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

    2011-01-01

    -like behaviour, NPY and galanin gene expression was studied in brains of mice subjected to chronic restraint stress (CRS) and concomitant treatment with the antidepressant fluoxetine (FLX). CRS caused a significant increase in depression-like behaviour that was associated with increased NPY mRNA levels......Stressful life events and chronic stress are implicated in the development of depressive disorder in humans. Neuropeptide Y (NPY) and galanin have been shown to modulate the stress response, and exert antidepressant-like effects in rodents. To further investigate these neuropeptides in depression...... in the medial amygdala. Concomitant FLX treatment reverted depression-like effects of CRS and led to significant increases in levels of NPY and galanin mRNA in the dentate gyrus, amygdala, and piriform cortex. These findings suggest that effects on NPY and galanin gene expression could play a role...

  10. Effects of previous physical exercise to chronic stress on long-term aversive memory and oxidative stress in amygdala and hippocampus of rats.

    Science.gov (United States)

    Dos Santos, Tiago Marcon; Kolling, Janaína; Siebert, Cassiana; Biasibetti, Helena; Bertó, Carolina Gessinger; Grun, Lucas Kich; Dalmaz, Carla; Barbé-Tuana, Florencia María; Wyse, Angela T S

    2017-02-01

    Since stressful situations are considered risk factors for the development of depression and there are few studies evaluating prevention therapies for this disease, in the present study we evaluated the effect of previous physical exercise in animals subjected to chronic variable stress (CVS), an animal model of depression, on behavior tasks. We also investigated some parameters of oxidative stress and Na(+), K(+)-ATPase activity, immunocontent and gene expression of alpha subunits in amygdala and hippocampus of rats. Young male rats were randomized into four study groups (control, exercised, stressed, exercised+stressed). The animals were subjected to controlled exercise treadmill for 20min,three times a week, for two months prior to submission to the CVS (40days). Results show that CVS impaired performance in inhibitory avoidance at 24h and 7days after training session. CVS induced oxidative stress, increasing reactive species, lipoperoxidation and protein damage, and decreasing the activity of antioxidant enzymes. The activity of Na(+), K(+)-ATPase was decreased, but the immunocontents and gene expression of catalytic subunits were not altered. The previous physical exercise was able to improve performance in inhibitory avoidance at 24h after training; additionally, exercise prevented oxidative damage, but was unable to reverse completely the changes observed on the enzymatic activities. Our findings suggest that physical exercise during the developmental period may protect against aversive memory impairment and brain oxidative damage caused by chronic stress exposure later in life.

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

    Science.gov (United States)

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

    2014-07-01

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

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

    Science.gov (United States)

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

    2012-03-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

    Chida, Yoichi; Hamer, Mark

    2008-01-01

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

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

    Science.gov (United States)

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

    2010-05-01

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

  16. 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 ...

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

    Science.gov (United States)

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

    2009-01-01

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

  18. A pharmacotherapeutic approach to the management of chronic posttraumatic stress disorder.

    Science.gov (United States)

    Spaulding, Adam Michael

    2012-10-01

    Due to relatively recent and ongoing world events (eg, terrorist attacks, wars, and natural disasters), there has been a shift in attention from some of the more common psychiatric illnesses to one of the more elusive, namely, posttraumatic stress disorder (PTSD). PTSD is a severe, and often chronic, condition that can lead to significant morbidity and mortality. Although originally a condition seen primarily among war veterans, PTSD is now becoming more prevalent in the general community. PTSD often presents concurrently with other conditions, such as depression, bipolar, anxiety/panic disorders, and alcohol and drug abuse. Because of this, PTSD often goes unrecognized and is underdiagnosed in clinical practice. Thus, an opportunity for pharmacist intervention exists, both in the institution and in the community. With proper education and training, pharmacists can be efficient in screening for signs and symptoms of PTSD, triaging appropriate patients, and can play an integral role in managing the diverse array of drug therapy options for PTSD.

  19. Moving beyond "sticks and stones": chronic psychological trauma predicts posttraumatic stress symptoms.

    Science.gov (United States)

    Jeter, Whitney K; Brannon, Laura A

    2014-01-01

    To date, trauma research has focused on the impact of physical trauma on posttraumatic stress (PTS) symptoms. Sometimes psychological trauma is measured with instances of physical trauma; however, less is known about solely psychological trauma. The current study addresses this by examining psychological trauma and PTS symptoms using the chronic relational trauma (CRT) model. The CRT model examines physical and possible concurrent psychological childhood, peer, and intimate partner trauma; however, psychological trauma alone has yet to be tested. A total of 232 female undergraduates (M age = 18.32, SD = 1.60) completed a series of questionnaires. Structural equation modeling indicated that childhood, peer, and intimate partner psychological trauma predict current PTS symptoms. Contributions of these findings are discussed.

  20. Prazosin reduces trauma-related nightmares in older men with chronic posttraumatic stress disorder.

    Science.gov (United States)

    Peskind, Elaine R; Bonner, Lauren T; Hoff, David J; Raskind, Murray A

    2003-09-01

    Trauma-related nightmares in posttraumatic stress disorder (PTSD) rarely respond to pharmacologic treatment. Neurobiologic data suggest that enhanced brain responsiveness to adrenergic stimulation may contribute to the pathophysiology of trauma-related nightmares in PTSD. Nine older men with chronic PTSD secondary to military or Holocaust trauma were prescribed the lipophilic alpha-1 adrenergic antagonist prazosin for treatment-resistant trauma-related nightmares. Prazosin 2 mg to 4 mg 1 hour before bedtime substantially reduced nightmares and moderately or markedly reduced overall PTSD severity in 8 of 9 subjects. Prazosin was well tolerated. These open-label results are consistent with demonstrated therapeutic efficacy of prazosin for PTSD nightmares and sleep disturbance in a recent placebo-controlled trial in Vietnam veterans.

  1. Initial community evenness favours functionality under selective stress.

    Science.gov (United States)

    Wittebolle, Lieven; Marzorati, Massimo; Clement, Lieven; Balloi, Annalisa; Daffonchio, Daniele; Heylen, Kim; De Vos, Paul; Verstraete, Willy; Boon, Nico

    2009-04-01

    Owing to the present global biodiversity crisis, the biodiversity-stability relationship and the effect of biodiversity on ecosystem functioning have become major topics in ecology. Biodiversity is a complex term that includes taxonomic, functional, spatial and temporal aspects of organismic diversity, with species richness (the number of species) and evenness (the relative abundance of species) considered among the most important measures. With few exceptions (see, for example, ref. 6), the majority of studies of biodiversity-functioning and biodiversity-stability theory have predominantly examined richness. Here we show, using microbial microcosms, that initial community evenness is a key factor in preserving the functional stability of an ecosystem. Using experimental manipulations of both richness and initial evenness in microcosms with denitrifying bacterial communities, we found that the stability of the net ecosystem denitrification in the face of salinity stress was strongly influenced by the initial evenness of the community. Therefore, when communities are highly uneven, or there is extreme dominance by one or a few species, their functioning is less resistant to environmental stress. Further unravelling how evenness influences ecosystem processes in natural and humanized environments constitutes a major future conceptual challenge.

  2. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity

    Science.gov (United States)

    Akimoto-Gunther, Luciene; Bonfim-Mendonça, Patrícia de Souza; Takahachi, Gisele; Irie, Mary Mayumi T.; Miyamoto, Sônia; Consolaro, Márcia Edilaine Lopes; Svidzinsk, Terezinha I. Estivalet

    2016-01-01

    We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC), including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI). Yeasts were isolated from 71 (26%) women: 23 (32.4%) with a positive culture but without symptoms (COL), 22 (31%) in an acute episode (VVC), and 26 (36.6%) with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture) comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC) than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels) and reduced antioxidant capacity can be host predisposing factors to RVVC. PMID:27415762

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

    Directory of Open Access Journals (Sweden)

    Michele Salanova

    2013-01-01

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

  4. Highlights Regarding Host Predisposing Factors to Recurrent Vulvovaginal Candidiasis: Chronic Stress and Reduced Antioxidant Capacity.

    Directory of Open Access Journals (Sweden)

    Luciene Akimoto-Gunther

    Full Text Available We studied host factors that could predispose women to develop recurrent vulvovaginal candidiasis (RVVC, including glycemia, insulin resistance, chronic stress, antioxidant capacity, overall immune status, local inflammation and vaginal microbiota. The presence of yeasts in vaginal culture was screened in 277 women, with or without signs and symptoms of VVC and RVVC. The presence of an inflammatory process and microbiota were analyzed through vaginal bacterioscopy and cervical-vaginal cytology, respectively. Fasting-blood samples were collected by standard venipuncture for biochemical analyses. Flow cytometry was employed to obtain the T helper/T cytotoxic lymphocyte ratio, and insulin resistance was assessed by the HOMA index (HI. Yeasts were isolated from 71 (26% women: 23 (32.4% with a positive culture but without symptoms (COL, 22 (31% in an acute episode (VVC, and 26 (36.6% with RVVC. C. albicans was the main yeast isolated in all clinical profiles. The control group (negative culture comprised 206 women. Diabetes mellitus and insulin resistance were more associated with the positive-culture groups (COL, VVC and RVVC than with negative ones. The RVVC group showed lower mean levels of cortisol than the control group and lower antioxidant capacity than all other groups. The T Helper/T cytotoxic lymphocyte ratio was similar in all groups. The RVVC group showed a similar level of vaginal inflammation to the control group, and lower than in the COL and VVC groups. Only the CVV group showed a reduction in vaginal lactobacillus microbiota. Our data suggest that both chronic stress (decreased early-morning cortisol levels and reduced antioxidant capacity can be host predisposing factors to RVVC.

  5. Direct and correlated effects of selection on flight after exposure to thermal stress in Drosophila melanogaster.

    Science.gov (United States)

    Krebs, Robert A; Thompson, Kimberly A

    2006-01-01

    To demonstrate how insects may adapt to ecologically relevant levels of heat stress, we performed artificial selection on the ability of Drosophila melanogaster to fly after an exposure to a high but non-lethal thermal stress. Both tolerance and intolerance to heat stress arose very quickly, as only a few generations of selection were necessary to cause significant separation between high and low lines for heat tolerance. Estimates of heritability based on the lines artificially selected for increased flight ability ranged from 0.024 to 0.052, while estimates of heritability based on the lines selected for the inability to fly after heat stress varied between 0.035 and 0.091. Reciprocal F1 crosses among these lines revealed strong additive effects of one or more autosomes and a weaker X-chromosome effect. This variation apparently affected flight specifically; neither survival to a more extreme stress nor knockdown by high temperature changed between lines selected for high and low heat tolerance as measured by flight ability. As the well-studied heat-shock response is associated with heat tolerance as measured by survival and knockdown, the aspects of the stress physiology that actually affect flight ability remains unknown.

  6. Potential neurobiological benefits of exercise in chronic pain and posttraumatic stress disorder: Pilot study.

    Science.gov (United States)

    Scioli-Salter, Erica; Forman, Daniel E; Otis, John D; Tun, Carlos; Allsup, Kelly; Marx, Christine E; Hauger, Richard L; Shipherd, Jillian C; Higgins, Diana; Tyzik, Anna; Rasmusson, Ann M

    2016-01-01

    This pilot study assessed the effects of cardiopulmonary exercise testing and cardiorespiratory fitness on plasma neuropeptide Y (NPY), allopregnanolone and pregnanolone (ALLO), cortisol, and dehydroepiandrosterone (DHEA), and their association with pain sensitivity. Medication-free trauma-exposed participants were either healthy (n = 7) or experiencing comorbid chronic pain/posttraumatic stress disorder (PTSD) (n = 5). Peak oxygen consumption (VO2) during exercise testing was used to characterize cardiorespiratory fitness. Peak VO2 correlated with baseline and peak NPY levels (r = 0.66, p exercise-induced changes in ALLO (r = 0.89, p exercise correlated with pain threshold 30 min after exercise (r = 0.65, p exercise-induced increases in ALLO correlated with pain tolerance 30 min after exercise (r = 0.64, p exercise-induced changes in cortisol and DHEA levels were inversely correlated with pain tolerance after exercise (r = -0.69, p exercise, which in turn relate to pain sensitivity. Future work will examine whether progressive exercise training increases cardiorespiratory fitness in association with increases in NPY and ALLO and reductions in pain sensitivity in chronic pain patients with PTSD.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  8. 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.

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

  10. 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.

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

    Directory of Open Access Journals (Sweden)

    Raquel Salazar-Lugo

    2015-12-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Renata Roland Teixeira

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

  14. Protective effects of ginsenoside Rg1 on chronic restraint stress induced learning and memory impairments in male mice.

    Science.gov (United States)

    Wang, Yuchan; Kan, Hongwei; Yin, Yanyan; Wu, Wangyang; Hu, Wen; Wang, Mingming; Li, Weiping; Li, Weizu

    2014-05-01

    Alzheimer's disease (AD) is one of the major neurological diseases of the elderly. Chronic stress, which can induce atrophy and functional impairments in several key brain areas such as the frontal cortex and hippocampus, plays an important role in the generation and progression of AD. Currently, there are no effective drug treatment options for preventing chronic stress induced learning and memory impairments and neuronal damage. Ginsenoside Rg1 (Rg1) is a steroidal saponin abundantly contained in ginseng. This study explored the neuroprotective effects of Rg1 on chronic restraint stress (CRS) induced learning and memory impairments in a mouse model. Our results showed that Rg1 (5mg/kg) significantly protected against learning and memory impairments induced by CRS in a Morris water maze. Besides, Rg1 (2, 5mg/kg) was able to decrease ROS generation and attenuate the neuronal oxidative damage in the frontal cortex and hippocampus CA1 in mice. Additionally, the inhibition of NOX2, p47phox and RAC1 expression is also involved in the action mechanisms of Rg1 in this experimental model. This study provided an experimental basis for the clinical application of Rg1 in chronic stress induced neuronal oxidative damage.

  15. Differential effects of chronic partial sleep deprivation and stress on serotonin-1A and muscarinic acetylcholine receptor sensitivity

    NARCIS (Netherlands)

    Roman, Viktor; Hagewoud, Roelina; Luiten, Paul G. M.; Meerlo, Peter

    2006-01-01

    Disrupted sleep and stress are often linked to each other, and considered as predisposing factors for psychopathologies such as depression. The depressed brain is associated with reduced serotonergic and enhanced cholinergic neurotransmission. In an earlier study, we showed that chronic sleep restri

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  17. Self-inflicted burns in patients with chronic combat-related post-traumatic stress disorder.

    Science.gov (United States)

    Bras, Marijana; Loncar, Zoran; Boban, Maja; Gregurek, Rudolf; Brajković, Lovorka; Tomicić, Hrvoje; Muljacić, Ante; Micković, Vlatko; Kalenić, Barbara

    2007-12-01

    This study examined self-inflicted burns in case series of four patients with chronic combat-related post-traumatic stress disorder (PTSD). Those patients were hospitalized in the Burn Unit of the University Hospital of Traumatology in Zagreb because of severe burns and had a premorbid psychiatric history of PTSD. Demographic data and information regarding the circumstances surrounding the incident, burn severity, treatment and outcomes of these patients were collected. The authors have analyzed possible impacts of the sensationalistic way in which media present cases of self-inflicted burning that induce other, new cases of this suicide type, known in the literature as "Werther's syndrome". The importance of multidisciplinary approach in the treatment of burn patients is stressed with emphasis on the important role of liaison psychiatrist in treating these patients. It is necessary to educate media people to avoid sensational reporting on this kind of events. Continuous psychiatric treatment of vulnerable individuals could be useful in prevention of self-inflicted burns.

  18. Antioxidants and chronic pancreatitis: theory of oxidative stress and trials of antioxidant therapy.

    Science.gov (United States)

    Grigsby, Brianna; Rodriguez-Rilo, Horacio; Khan, Khalid

    2012-04-01

    Chronic pancreatitis (CP) is an inflammatory disease characterized by the progressive destruction of pancreatic tissue and resulting in pancreatic exocrine and endocrine insufficiency. Increased oxidative stress has been implicated as a potential mechanism in its etiology and pathology. A number of studies have demonstrated that CP patients have a compromised antioxidant status, which may be a contributing factor to the enhanced oxidative state associated with the disease. Nutrition is an essential consideration in the treatment of CP, especially since diet is a source of several antioxidants and cofactors required for the production of cellular antioxidant enzymes. Many CP patients have an inadequate intake of macro and micronutrients because of abdominal pain and discomfort, which often increase postprandially and discourage eating. Exocrine insufficiency leads to further complications by preventing adequate digestion and absorption of ingested food, thus causing even greater deficiencies and impairment of antioxidant status. The aims of this article are to review the oxidative stress model of CP and to examine the evidence for nutrition, and, particularly, antioxidants, in the treatment of CP.

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

    Science.gov (United States)

    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.

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

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    Bárbara B. Garrido-Suárez

    2015-12-01

    Full Text Available Context: Ovarian hormone deficiency observed in menopausal women increases the production of reactive oxygen species, which could be implicated in central sensitization subjacent in chronic functional pain syndromes. Aims: To examine the hyperalgesic state induced by ovariectomy in adult rats and its relation to some oxidative stress outcomes. Methods: The female Wistar rats were divided into normal, sham ovariectomized (OVX and OVX groups, which were tested for mechanical and thermal hypernociception during 6 weeks and a single acetic acid-induced test 6 weeks after surgery. Redox biomarkers determinations of superoxide dismutase (SOD enzyme activity, glutathione (GSH and nitrates/nitrites as an indicator of nitric oxide (NO concentrations were determined in the brain and cerebellum of 6 animals of each group. Results: Exclusivity OVX rats developed a robust state of mechanical hypernociception and allodynia in the abdomen, hindlimbs and proximal tail. Besides, thermal pain thresholds (hot plate decreased. That was established 3-4 weeks after OVX and lasted for the 6 weeks of the experiment. Increases in visceral sensitivity were also observed in OVX rats. SOD enzyme activity decreased in OVX rats, which showed major deficit for this enzymatic defense under visceral inflammatory injury. However GSH concentrations were increased in brain of OVX animals that allow the balance during acute inflammation. NO concentrations were raised only in OVX rats exposure to chemical inflammatory injury. Conclusions: OVX in rats provide a useful model, which mimics the functional pain in females that could be related with brain oxidative stress.

  1. Effect of Xiaoyaosan Decoction on Learning and Memory Deficit in Rats Induced by Chronic Immobilization Stress

    Directory of Open Access Journals (Sweden)

    Zhen-Zhi Meng

    2013-01-01

    Full Text Available Xiaoyaosan (XYS decoction is a famous prescription which can protect nervous system from stress and treat liver stagnation and spleen deficiency syndrome (LSSDS. In this experiment, we observed the effect of XYS decoction on chronic immobilization stress (CIS induced learning and memory deficit in rats from behaviors and changes of proteins in hippocampus. We used XYS decoction to treat CIS induced learning and memory deficit in rats with rolipram as positive control, used change of body weight and behavioral tests to determine whether the rats have LSSDS and have learning and memory deficit or not. We used Western blotting to determine the content of postsynaptic density protein 95 (PSD-95 and synaptophysin (SYP in hippocampus. Results showed that XYS could improve the situation of slow weight gain induced by CIS, improve the ability of learning and memory, reverse the symptom of liver stagnation and spleen deficiency syndrome (LSSDS in rats, and increase the levels of PSD-95 and SYP on the hippocampal nerve synapses. These findings suggested that XYS decoction may be helpful in reversing CIS induced learning and memory deficit by increasing the levels of PSD-95 and SYP on the hippocampal nerve synapses and improving synaptic plasticity.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2014-03-03

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

  3. 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.

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

    Science.gov (United States)

    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.

  5. Mechanical stress as the common denominator between chronic inflammation, cancer and Alzheimer’s disease

    Directory of Open Access Journals (Sweden)

    Marcel eLevy Nogueira

    2015-09-01

    Full Text Available The pathogenesis of common diseases such as Alzheimer’s disease (AD and cancer are currently poorly understood. Inflammation is a common risk factor for cancer and AD. Recent data, provided by our group and from others, demonstrate that increased pressure and inflammation are synonymous. There is a continuous increase in pressure from inflammation to fibrosis and then cancer. This in line with the numerous papers reporting high interstitial pressure in cancer. But most authors focus on the role of pressure in the lack of delivery of chemotherapy in the center of the tumor. Pressure may also be a key factor in carcinogenesis. Increased pressure is responsible for oncogene activation and cytokine secretion. Accumulation of mechanical stress plays a key role in the development of diseases of old age such as cardiomyopathy, atherosclerosis and osteoarthritis. Growing evidence suggest also a possible link between mechanical stress in the pathogenesis of AD. The aim of this review is to describe environmental and endogenous mechanical factors possibly playing a pivotal role in the mechanism of chronic inflammation, AD and cancer.

  6. Role of oxidative stress & transient receptor potential in chronic obstructive pulmonary disease

    Directory of Open Access Journals (Sweden)

    Protiti Bose

    2015-01-01

    Full Text Available Chronic obstructive pulmonary disease (COPD affect millions of people worldwide and is known to be one of the leading causes of death. The highly sensitive airways protect themselves from irritants by cough and sneeze which propel endogenous and exogenous substances to minimize airway noxious effects. One noxious effect of these substances is activation of peripheral sensory nerve endings of nociceptor neurons innervating these airways lining thus transmitting dangerous signals from the environment to the central nervous system (CNS. Nociceptor neurons include transient receptor potential (TRP ion channels, especially the vanilloid and ankyrin subfamilies, TRPV1/A1 which can be activated by noxious chemical challenges in models of airways disease. As oxidative stress may activate airways sensory neurons and contribute to COPD exacerbations we sought to review the role that TRP channel activation by oxidative signals may have on airway responses. i0 t would be prudent to target the TRP channels with antagonists and lower systemic oxidative stress with agents that can modulate TRP expression and boost the endogenous levels of antioxidants for treatment and management of COPD.

  7. 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.

  8. Chronic effects of methylmercury on the urinary excretion of catecholamines and their responses to hypoglycemic stress

    Energy Technology Data Exchange (ETDEWEB)

    Kabuto, M. (Japan National Inst. of Environmental Studies (NIES), Tsukuba, Ibaraki (Japan). Dept. of Environmental Health)

    1991-02-01

    Five male Wistar rats were treated with methylmecury chloride (MMC) and compared with five agematched control rats. A dose of 10 mg/kg was given three times. The chronic effects of the MMC administration on the urinary output of catecholamines (norepinephrine (NE), epinephrine (E) and dopamine (DA)) were measured for 50 days. On the 69th day after MMC administration, the rats were examined for insulin-induced hypoglycemic stress. On the 90th day, the animals were decapitated and various organs were weighted and serum thyroid hormones (thyroid stimulating hormone (TSH) and total and free thyroxine (T4)) were measured. Decreases in DA excretion and DA response to stress were observed in the MMC-treated group. Inflammation of the kidney was also found, suggesting MMC-induced damage to the renal tubular region, the apparent site of renal DA synthesis. The MMC group and the control group showed differential NE and E response patterns. The lowered baseline excretion of NE appeared to continue even 70 days after MMC administration, while the difference in E excretion between the two groups disappeared 1 month after MMC administration. Both NE and E showed normal responsiveness to hypoglycemic stress induced by insulin. All serum TSH and total and free T4 baseline levels showed slight increases, and the thyroid gland weights in the MMC group were slightly heavier. These findings suggest a rather hyperthyroid state after the initial acute phase suppression, as suggested by the previous examinations. Thus, these findings suggest long-lasting effects of methylmercury administration, especially on renal DA synthesis. Baseline urinary excretion of NE and thyroid function could also be affected for a long time. (orig.).

  9. Self-esteem, narcissism, and stressful life events: Testing for selection and socialization.

    Science.gov (United States)

    Orth, Ulrich; Luciano, Eva C

    2015-10-01

    We examined whether self-esteem and narcissism predict the occurrence of stressful life events (i.e., selection) and whether stressful life events predict change in self-esteem and narcissism (i.e., socialization). The analyses were based on longitudinal data from 2 studies, including samples of 328 young adults (Study 1) and 371 adults (Study 2). The effects of self-esteem and narcissism were mutually controlled for each other and, moreover, controlled for effects of depression. After conducting the study-level analyses, we meta-analytically aggregated the findings. Self-esteem had a selection effect, suggesting that low self-esteem led to the occurrence of stressful life events; however, this effect became nonsignificant when depression was controlled for. Regardless of whether depression was controlled for or not, narcissism had a selection effect, suggesting that high narcissism led to the occurrence of stressful life events. Moreover, stressful life events had a socialization effect on self-esteem, but not on narcissism, suggesting that the occurrence of stressful life events decreased self-esteem. Analyses of trait-state models indicated that narcissism consisted almost exclusively of perfectly stable trait variance, providing a possible explanation for the absence of socialization effects on narcissism. The findings have significant implications because they suggest that a person's level of narcissism influences whether stressful life events occur, and that self-esteem is shaped by the occurrence of stressful life events. Moreover, we discuss the possibility that depression mediates the selection effect of low self-esteem on stressful life events. (PsycINFO Database Record

  10. Effects of acute and chronic physical exercise and stress on different types of memory in rats

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    Pâmela Billig Mello

    2008-06-01

    Full Text Available Here we study the effect of acute and chronic physical exercise in a treadmill and of daily stress (because forced exercise involves a degree of stress during 2 or 8 weeks on different types of memory in male Wistar rats. The memory tests employed were: habituation in an open field, object recognition and spatial learning in the Morris water maze. Daily foot-shock stress enhanced habituation learning after 2 but not after 8 weeks; it hindered both short- (STM and long-term memory (LTM of the recognition task at 2 weeks but only STM after 8 weeks and had no effect on spatial learning after either 2 or 8 weeks. Acute but not chronic exercise also enhanced habituation in the open field and hindered STM and LTM in the recognition task. Chronic exercise enhanced one important measure of spatial learning (latency to escape but not others. Our findings indicate that some care must be taken when interpreting effects of forced exercise on brain parameters since at least part of them may be due to the stress inherent to the training procedure.Neste trabalho estudamos os efeitos do exercício forçado diário em esteira rolante e da exposição diária ao estresse (porque o exercício forçado envolve um certo grau de estresse durante 2 ou 8 semanas em diferentes tipos de memória em ratos Wistar machos. Os testes de memória utilizados foram: habituação da exploração em um campo aberto, reconhecimento de objetos, e memória espacial no labirinto aquático de Morris. O estresse diário facilitou a memória de habituação, os animais aprenderam após 2 mas não após 8 semanas; houve prejuízo na memória curta (STM e de longa duração (LTM no teste de reconhecimento em 2 semanas, mas somente de STM após 8 semanas; não houve nenhum efeito na memória espacial após 2 ou 8 semanas. O protocolo do exercício facilitou também a memória de habituação no campo aberto após 2 mas não após 8 semanas; prejudicou STM e LTM na tarefa do reconhecimento

  11. Protein carbonyl: An oxidative stress marker in gingival crevicular fluid in healthy, gingivitis, and chronic periodontitis subjects

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    Avani R Pradeep

    2013-01-01

    Full Text Available Background: A defined role for reactive oxygen species (ROS in the tissue destruction that characterizes periodontitis has been described. Protein carbonyl (PC is the most widely used biomarker for oxidative damage to proteins, and reflects cellular damage induced by multiple forms of ROS. The purpose of this study is to determine the presence of PC in gingival crevicular fluid (GCF in healthy, gingivitis, and chronic periodontitis (CP subjects and to find an association, if any. Materials and Methods: A total number of 75 subjects (38 males and 37 females were selected based on their clinical parameters into three groups: Group 1 (25 healthy subjects, Group 2 (25 gingivitis subjects, and Group 3 (25 CP subjects. GCF samples were collected to estimate the levels of PC. Results: The PC concentration in GCF was highest in subjects with CP as compared to gingivitis and healthy subjects and a significant association was observed between GCF PC levels and all periodontal parameters. Conclusion: There was an increase in PC levels in GCF as the disease process progressed from healthy to gingivitis and CP, suggesting a role for increased oxidative stress in CP.

  12. Practical considerations and patient selection for intrathecal drug delivery in the management of chronic pain

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    Saulino M

    2014-11-01

    Full Text Available Michael Saulino,1,2 Philip S Kim,3,4 Erik Shaw5 1MossRehab, Elkins Park, PA, USA; 2Department of Rehabilitation Medicine, Jefferson Medical College, Philadelphia, PA, USA; 3Helen F Graham Cancer Center, Christiana Care Health System, Newark, DE, USA; 4Center for Interventional Pain Spine, LLC., Bryn Mawr, PA, USA; 5Shepherd Pain Institute, Shepherd Center, Atlanta, GA, USA Abstract: Chronic pain continues to pose substantial and growing challenges for patients, caregivers, health care professionals, and health care systems. By the time a patient with severe refractory pain sees a pain specialist for evaluation and management, that patient has likely tried and failed several nonpharmacologic and pharmacologic approaches to pain treatment. Although relegated to one of the interventions of “last resort”, intrathecal drug delivery can be useful for improving pain control, optimizing patient functionality, and minimizing the use of systemic pain medications in appropriately selected patients. Due to its clinical and logistical requirements, however, intrathecal drug delivery may fit poorly into the classic pain clinic/interventional model and may be perceived as a "critical mass" intervention that is feasible only for large practices that have specialized staff and appropriate office resources. Potentially, intrathecal drug delivery may be more readily adopted into larger practices that can commit the necessary staff and resources to support patients' needs through the trialing, initiation, monitoring, maintenance, and troubleshooting phases of this therapy. Currently, two agents – morphine and ziconotide – are approved by the United States Food and Drug Administration for long-term intrathecal delivery. The efficacy and safety profiles of morphine have been assessed in long-term, open-label, and retrospective studies of >400 patients with chronic cancer and noncancer pain types. The efficacy and safety profiles of ziconotide have been

  13. D-cycloserine for treatment of numbing and avoidance in chronic post traumatic stress disorder: A randomized, double blind, clinical trial

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    Abbas Attari

    2014-01-01

    Full Text Available Background: Posttraumatic stress disorder (PTSD tends to follow a chronic and treatment resistant course. Avoidance and numbing are symptoms associated with chronicity and impaired life quality. As D-cycloserine (DCS can facilitate extinction of conditioned fear, we aimed to investigate the efficacy and tolerability of DCS for the treatment of numbing and avoidance in chronic PTSD. Materials and Methods: This was an 11-week, double-blind, cross-over trial conducted in 2012 and 2013, in out-patient University psychiatry clinics. The studied population was selected randomly among outpatients with chronic combat-related PTSD (based on DSM-IV-TR criteria for chronic PTSD, who were males over 18 and <65 years of age (n = 319. Seventy six eligible patients were randomly assigned to two groups. Patients entered a 1-week run-in period. The groups received either an add-on treatment of DCS (50 mg daily, or placebo (4-week. After a 2-week washout, the groups received cross-over treatments (4-week. Clinical, paraclinical assessments, and clinician administered PTSD scale (CAPS were performed at baseline, and at the end of the 1 st , 5 th , and 11 th week. Side-effects were also evaluated. The overall number of avoidance and numbing symptoms, symptom frequency, and symptom intensity were measured separately. Results: Neither frequency nor number of symptoms was significantly influenced. However, DCS treatment demonstrates a significant decrease in intensity of avoidance/numbing symptoms, and improvement in function (mean [standard error] = −4.2 [1.5], P = 0.008. Side-effects were not statistically remarkable. Conclusion: D-cycloserine can help as an adjunctive treatment to alleviate numbing and avoidance in combat-related chronic PTSD.

  14. EFFECTS OF CHRONIC STRESS ON THE ACTIVITIES OF SOD, GSH-Px AND MDA LEVEL IN FEMALE RATS' BRAIN

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    王莹; 杨东伟; 谢雯; 庞炜; 蒋马莉; 韩太真

    2002-01-01

    Objective To observe the effects of chronic emotional stress on the activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and malonialdehyde (MDA) level in female rats' brain. Methods The rats were randomly divided into 4 groups: normal control group (group N), emotional stress group (group E), emotional stress + pregnancy group (group E+P) and regularly drinking group (group R). Emotional stress in rats was induced by training rats with empty drinking bottles. Having been finished the stress procedure, the brain was taken out and homogenized. Then the activities of SOD, GSH-Px and MDA level were measured. Results Compared to group N, both the activities of SOD in brain tissues of group E and group E+P were significantly decreased (P<0.05 and P<0.01, respectively) while the MDA level increased (P<0.05). However, the extent of changes in group E+P was more obvious than that in E. GSH-Px activities in E+P and E were significantly changed. However, the GSH-Px activity in E+P was decreased (P<0.05) while the activity in E increased (P<0.05).Conclusion The chronic emotional stress can reduce the antioxidative system by decreasing the antioxidative enzyme activity and potentiating the lipid peroxidation in the brain. It is also suggested that the combination of emotional stress and pregnancy can augment the oxidative damage in rats' brain.

  15. The Association of Malnutrition and Chronic Stress Models Does Not Present Overlay Effects in Male Wistar Rats

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    Camila Gracyelle de Carvalho Lemes

    2016-09-01

    Full Text Available Chronic stress and protein-energy malnutrition (PEM are both social problems resulting in physiological and behavioral alterations. In this present study an associative effects of PEM and chronic stress were evaluated through in Wistar rats. Four groups were established: standard diet– 19% of protein (Std; Std + stress; PEM–6% of protein and PEM + stress. In these groups were assessed physical, nutritional, hematological, histological parameters and anxiety-like behavior. There were a reduction of food intake, body mass and relative weight of the heart and thymus in the PEM group. The liver of the PEM animals presented a degenerative condition with steatosis and Kupffer cell hypertrophy and, additionally, a significant decrease in hematocrit percentages, in the number of red blood cells and in the concentration of hemoglobin and total protein. In those animals under stress and Std diet, there was observed an increase of the relative adrenal weights, an acute condition of leukocytosis with a predominance of neutrophils and an increase in the anxiety-like behavior. There was no overlapping/interaction among the anthropometric, biochemical, hematological and histological effects using PEM and stress in Wistar rats. The effects observed under experimental condition were those related to either PEM or stress, independently.

  16. THE EFFECTS OF ACUTE AND CHRONIC STRESS ON ERYTHROCYTE DYNAMIC IN COMBINATION WITH ß–ADRENERGIC RECEPTORS BLOCKADE IN RATS

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    Lucian Hritcu

    2005-08-01

    Full Text Available : 3 consecutive days propranolol hydrochloride administration (5 mg/kg b.w., subcutaneous injections under acute and chronic stress conditions causes changes of peripheral erythrocyte distribution in rats. The effects of acute stress and its combination with ȕ-adrenergic receptor blockade on erythrocyte dynamic were more pregnant beside the effects of chronic stress and its combination with ȕ-adrenergic receptor blockade, respectively. ȕ-adrenergic mechanisms were shown to be involved in regulation of erythrocyte dynamic in acute and chronic stress response.

  17. Differential regulation of Neuropeptide Y (NPY in the amygdala and prefrontal cortex during recovery from chronic variable stress (CVS

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    Jennifer Lynne McGuire

    2011-09-01

    Full Text Available Accumulating evidence from clinical studies and pre-clinical animal models supports a role for neuropeptide Y (NPY in adaptive emotional response following stress. The long-term impact of stress, particularly chronic stress, on availability and function of resilience factors such as NPY may be critical to understanding the etiology of stress-related psychopathology. In these studies, we examined expression of NPY during recovery from a chronic variable stress (CVS model of repetitive trauma in rats. Due to the importance of amygdala and prefrontal cortex in regulating emotional responses, we predicted chronic changes in NPY expression could contribute to persistent behavioral deficits seen in this model. Consistent with the hypothesis, ELISA for NPY peptide identified a significant reduction in NPY at the delayed (7 days recovery timepoint. Interestingly, a significant increase in prefrontal NPY was observed at the same recovery timepoint.. The mRNA expression for NPY was not changed in the amygdala or PFC, although there was a modest but not statistically significant increase in NPY mRNA at the delayed recovery timepoint in the prefrontal cortex. The observed changes in NPY expression are consistent with maladaptive coping and enhanced emotionality, due to the nature of NPY signaling within these respective regions, and the nature of reciprocal connections between amygdala and prefrontal cortex.

  18. Effects of interspecific interaction-linked habitat factors on moose resource selection and environmental stress.

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    Bao, Heng; Fryxell, John M; Liu, Hui; Dou, Hongliang; Ma, Yingjie; Jiang, Guangshun

    2017-01-27

    Resource selection of herbivores is a complex ecological process that operates in relation to biological or non-biological factors, which may affect the feeding and movement, and subsequently their spatial distribution and environmental stress. Here, we estimated moose (Alces alces cameloides) resource selection for habitat variables and the effect of interspecific interactions related to roe deer (Capreolus pygargus bedfordi) on its population distribution and environmental stress in the Khingan Mountain region of northeast China at local and regional scales. Different response patterns of moose resource selection, spatial distribution, and environmental stress to interspecific interaction-linked habitat factors were shown at the two scales. A general ecological chain, response of moose to interspecific interaction-linked habitat factors, was exhibited at the regional scale, and at the local scale, heterogeneous responses, linkages of habitat selection and environmental stress of moose population might be driven by different interspecific interaction patterns. Our study firstly suggested that moose resource selection, food availability, diet quality, population density and environmental stress indicators were impacted by interactions with the distribution of other sympatric herbivore species and showed differences in ecological response chains at various spatial scales. These findings are useful for sympatric herbivore assembly conservation, habitat quality monitoring and management.

  19. Selection of arabica coffee progenies tolerant to heat stress

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    Alexsandro Lara Teixeira

    2015-07-01

    Full Text Available Due to high temperatures, practically all coffee farms in the state of Rondonia are of the C. canephora species. Thus, importing arabica coffee from other states becomes necessary for composition of blends, as well as for the specialty or gourmet coffee market. The purpose of this study was to select arabica coffee genotypes that exhibit satisfactory agronomic performance under high temperature conditions. The experiment was conducted in OuroPreto do Oeste, RO, Brazil, with mean annual temperature of 25.8°C and mean annual rainfall of 2300mm year-1. The experiment was composed of 114 arabica coffee genotypes, with 103 progenies and eleven control cultivars, provided by EPAMIG. A randomized block experimental design was used with three replications, spacing of 3.0x1.0 meters and five plants per plot. All the crop seasons showed significant difference for the green coffee yield trait. In joint analysis, significant differences were detected among progenies and control cultivars. In the average of the four harvests, green coffee yield was 32.38 bags ha-1. The cultivars 'CatuaíVermelho IAC 15', 'Obatã IAC 1669-20' and 'Catucaí Amarelo 2SLCAK' stood out, achieving yields greater than 40 bags ha-1. The gain obtained from selection was 14.33 bags ha-1, which is equivalent to an increase of 44.04% in production of green coffee. The progeny H514-7-10-6-2-3-9 stood out with an average yield of 51.20 bags ha-1. In regard to maturation cycle, 56% of the progenies were classified as early maturity and 44% as medium maturity. Late maturity genotypes were not observed

  20. Glucocorticoids regulation of FosB/ΔFosB expression induced by chronic opiate exposure in the brain stress system.

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    Daniel García-Pérez

    Full Text Available Chronic use of drugs of abuse profoundly alters stress-responsive system. Repeated exposure to morphine leads to accumulation of the transcription factor ΔFosB, particularly in brain areas associated with reward and stress. The persistent effects of ΔFosB on target genes may play an important role in the plasticity induced by drugs of abuse. Recent evidence suggests that stress-related hormones (e.g., glucocorticoids, GC may induce adaptations in the brain stress system that is likely to involve alteration in gene expression and transcription factors. This study examined the role of GC in regulation of FosB/ΔFosB in both hypothalamic and extrahypothalamic brain stress systems during morphine dependence. For that, expression of FosB/ΔFosB was measured in control (sham-operated and adrenalectomized (ADX rats that were made opiate dependent after ten days of morphine treatment. In sham-operated rats, FosB/ΔFosB was induced after chronic morphine administration in all the brain stress areas investigated: nucleus accumbens(shell (NAc, bed nucleus of the stria terminalis (BNST, central amygdala (CeA, hypothalamic paraventricular nucleus (PVN and nucleus of the solitary tract noradrenergic cell group (NTS-A(2. Adrenalectomy attenuated the increased production of FosB/ΔFosB observed after chronic morphine exposure in NAc, CeA, and NTS. Furthermore, ADX decreased expression of FosB/ΔFosB within CRH-positive neurons of the BNST, PVN and CeA. Similar results were obtained in NTS-A(2 TH-positive neurons and NAc pro-dynorphin-positive neurons. These data suggest that neuroadaptation (estimated as accumulation of FosB/ΔFosB to opiates in brain areas associated with stress is modulated by GC, supporting the evidence of a link between brain stress hormones and addiction.

  1. Chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala.

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    Li, Ming-Jia; Liu, Ling-Yu; Chen, Lin; Cai, Jie; Wan, You; Xing, Guo-Gang

    2017-04-01

    Exacerbation of pain by chronic stress and comorbidity of pain with stress-related psychiatric disorders, including anxiety and depression, represent significant clinical challenges. However, the underlying mechanisms still remain unclear. Here, we investigated whether chronic forced swim stress (CFSS)-induced exacerbation of neuropathic pain is mediated by the integration of stress-affect-related information with nociceptive information in the central nucleus of the amygdala (CeA). We first demonstrated that CFSS indeed produces both depressive-like behaviors and exacerbation of spared nerve injury (SNI)-induced mechanical allodynia in rats. Moreover, we revealed that CFSS induces both sensitization of basolateral amygdala (BLA) neurons and augmentation of long-term potentiation (LTP) at the BLA-CeA synapse and meanwhile, exaggerates both SNI-induced sensitization of CeA neurons and LTP at the parabrachial (PB)-CeA synapse. In addition, we discovered that CFSS elevates SNI-induced functional up-regulation of GluN2B-containing NMDA (GluN2B-NMDA) receptors in the CeA, which is proved to be necessary for CFSS-induced augmentation of LTP at the PB-CeA synapse and exacerbation of pain hypersensitivity in SNI rats. Suppression of CFSS-elicited depressive-like behaviors by antidepressants imipramine or ifenprodil inhibits the CFSS-induced exacerbation of neuropathic pain. Collectively, our findings suggest that CFSS potentiates synaptic efficiency of the BLA-CeA pathway, leading to the activation of GluN2B-NMDA receptors and sensitization of CeA neurons, which subsequently facilitate pain-related synaptic plasticity of the PB-CeA pathway, thereby exacerbating SNI-induced neuropathic pain. We conclude that chronic stress exacerbates neuropathic pain via the integration of stress-affect-related information with nociceptive information in the CeA.

  2. Chronic stress alters the dendritic morphology of callosal neurons and the acute glutamate stress response in the rat medial prefrontal cortex.

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    Luczynski, Pauline; Moquin, Luc; Gratton, Alain

    2015-01-01

    We have previously reported that interhemispheric regulation of medial prefrontal cortex (PFC)-mediated stress responses is subserved by glutamate (GLU)- containing callosal neurons. Evidence of chronic stress-induced dendritic and spine atrophy among PFC pyramidal neurons led us to examine how chronic restraint stress (CRS) might alter the apical dendritic morphology of callosal neurons and the acute GLU stress responses in the left versus right PFC. Morphometric analyses of retrogradely labeled, dye-filled PFC callosal neurons revealed hemisphere-specific CRS-induced dendritic retraction; whereas significant dendritic atrophy occurred primarily within the distal arbor of left PFC neurons, it was observed within both the proximal and distal arbor of right PFC neurons. Overall, CRS also significantly reduced spine densities in both hemispheres with the greatest loss occurring among left PFC neurons, mostly at the distal extent of the arbor. While much of the overall decrease in dendritic spine density was accounted by the loss of thin spines, the density of mushroom-shaped spines, despite being fewer in number, was halved. Using microdialysis we found that, compared to controls, basal PFC GLU levels were significantly reduced in both hemispheres of CRS animals and that their GLU response to 30 min of tail-pinch stress was significantly prolonged in the left, but not the right PFC. Together, these findings show that a history of chronic stress alters the dendritic morphology and spine density of PFC callosal neurons and suggest a mechanism by which this might disrupt the interhemispheric regulation of PFC-mediated responses to subsequent stressors.

  3. Effects of chronic stress in adolescence on learned fear, anxiety, and synaptic transmission in the rat prelimbic cortex.

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    Negrón-Oyarzo, Ignacio; Pérez, Miguel Ángel; Terreros, Gonzalo; Muñoz, Pablo; Dagnino-Subiabre, Alexies

    2014-02-01

    The prelimbic cortex and amygdala regulate the extinction of conditioned fear and anxiety, respectively. In adult rats, chronic stress affects the dendritic morphology of these brain areas, slowing extinction of learned fear and enhancing anxiety. The aim of this study was to determine whether rats subjected to chronic stress in adolescence show changes in learned fear, anxiety, and synaptic transmission in the prelimbic cortex during adulthood. Male Sprague Dawley rats were subjected to seven days of restraint stress on postnatal day forty-two (PND 42, adolescence). Afterward, the fear-conditioning paradigm was used to study conditioned fear extinction. Anxiety-like behavior was measured one day (PND 50) and twenty-one days (PND 70, adulthood) after stress using the elevated-plus maze and dark-light box tests, respectively. With another set of rats, excitatory synaptic transmission was analyzed with slices of the prelimbic cortex. Rats that had been stressed during adolescence and adulthood had higher anxiety-like behavior levels than did controls, while stress-induced slowing of learned fear extinction in adolescence was reversed during adulthood. As well, the field excitatory postsynaptic potentials of stressed adolescent rats had significantly lower amplitudes than those of controls, although the amplitudes were higher in adulthood. Our results demonstrate that short-term stress in adolescence induces strong effects on excitatory synaptic transmission in the prelimbic cortex and extinction of learned fear, where the effect of stress on anxiety is more persistent than on the extinction of learned fear. These data contribute to the understanding of stress neurobiology.

  4. Post-Traumatic Stress Disorder and the Military: A Selected Bibliography

    Science.gov (United States)

    2008-03-01

    ProQuest Russell, Mark C. “Treating Combat-Related Stress Disorders : A Multiple Case Study Utilizing Eye Movement Desensitization and Reprocessing ( EMDR ...use, PTSD, and generalized anxiety disorder . http://www.pdhealth.mil/mhsa.asp. U.S. Department of Veterans Affairs, National Center for Post...i POST-TRAUMATIC STRESS DISORDER AND THE MILITARY A Selected Bibliography Compiled by Lori M. Sekela U.S. Army War College Library Carlisle Barracks

  5. Stress selectively and lastingly promotes learning of context-related high arousing information.

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    Smeets, Tom; Wolf, Oliver T; Giesbrecht, Timo; Sijstermans, Kevin; Telgen, Sebastian; Joëls, Marian

    2009-09-01

    The secretion of adrenal stress hormones in response to acute stress is known to affect learning and memory, particularly for emotionally arousing memory material. Here, we investigated whether stress-induced modulation of learning and memory performance depends on (i) the conceptual relatedness between the material to be learned/remembered and the stressor and (ii) the timing of stress exposure versus learning phase. Participants learned stressor-related and stressor-unrelated words of varying arousal 1h prior to, immediately following, or 2h after exposure to the Trier Social Stress Test (all groups n=16). Twenty-four hours later, delayed free recall was assessed. Cortisol and alpha-amylase were sampled to evaluate if concurrent stress-induced raised glucocorticoid levels and high adrenergic activity are implicated in modulating learning performance. Our results demonstrate that immediate and delayed post-stress learning selectively enhanced the learning and delayed recall of stressor-related high arousing words. This enhancing effect was strongly associated with concurrent stress-induced cortisol and sympathetic activity. Our data suggest that when to-be-learned information is conceptually related to a stressor and considered important (i.e., arousing) by the individual, learning under stressful circumstances results in improved memorability afterwards.

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

    Energy Technology Data Exchange (ETDEWEB)

    Kaphalia, Lata [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Boroumand, Nahal [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Hyunsu, Ju [Department of Preventive Medicine and Community Health, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Kaphalia, Bhupendra S., E-mail: bkaphali@utmb.edu [Department of Pathology, The University of Texas Medical Branch, Galveston, TX 775555 (United States); Calhoun, William J. [Department of Internal Medicine, The University of Texas Medical Branch, Galveston, TX 775555 (United States)

    2014-06-01

    Consumption and over-consumption of alcoholic beverages are well-recognized contributors to a variety of pulmonary disorders, even in the absence of intoxication. The mechanisms by which alcohol (ethanol) may produce disease include oxidative stress and prolonged endoplasmic reticulum (ER) stress. Many aspects of these processes remain incompletely understood due to a lack of a suitable animal model. Chronic alcohol over-consumption reduces hepatic alcohol dehydrogenase (ADH), the principal canonical metabolic pathway of ethanol oxidation. We therefore modeled this situation using hepatic ADH-deficient deer mice fed 3.5% ethanol daily for 3 months. Blood ethanol concentration was 180 mg% in ethanol fed mice, compared to < 1.0% in the controls. Acetaldehyde (oxidative metabolite of ethanol) was minimally, but significantly increased in ethanol-fed vs. pair-fed control mice. Total fatty acid ethyl esters (FAEEs, nonoxidative metabolites of ethanol) were 47.6 μg/g in the lungs of ethanol-fed mice as compared to 1.5 μg/g in pair-fed controls. Histological and immunohistological evaluation showed perivascular and peribronchiolar lymphocytic infiltration, and significant oxidative injury, in the lungs of ethanol-fed mice compared to pair-fed controls. Several fold increases for cytochrome P450 2E1, caspase 8 and caspase 3 found in the lungs of ethanol-fed mice as compared to pair-fed controls suggest role of oxidative stress in ethanol-induced lung injury. ER stress and unfolded protein response signaling were also significantly increased in the lungs of ethanol-fed mice. Surprisingly, no significant activation of inositol-requiring enzyme-1α and spliced XBP1 was observed indicating a lack of activation of corrective mechanisms to reinstate ER homeostasis. The data suggest that oxidative stress and prolonged ER stress, coupled with formation and accumulation of cytotoxic FAEEs may contribute to the pathogenesis of alcoholic lung disease. - Highlights: • Chronic

  7. 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

  8. 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.

  9. Chronic stress accelerates ligature-induced periodontitis by suppressing glucocorticoid receptor-α signaling.

    Science.gov (United States)

    Lu, Huaixiu; Xu, Minguang; Wang, Feng; Liu, Shisen; Gu, Jing; Lin, Songshan; Zhao, Lisheng

    2016-03-25

    Periodontitis is a common chronic inflammatory disease. Recent studies have shown that chronic stress (CS) might modulate periodontal disease, but there are few models of CS-induced periodontitis, and the underlying mechanisms are unclear. The present study established a rat model of periodontitis associated with CS induced by nylon thread ligatures. The severity of periodontitis was evaluated in this model by radiographic and pathological examination. The inflammatory reaction indicated by the elevated serum levels of interleukin (IL)-1β, IL-6 and IL-8 was assessed by enzyme-linked immunosorbent assay. Toll-like receptor-4 (TLR4) and glucocorticoid receptor-α (GR-α) expressions were detected by reverse transcriptase-PCR and western blotting. Open-field tests and serum corticosterone were used to evaluate CS. The results showed that CS induced behavioral changes and increased corticosterone levels of the animals with periodontitis. CS stimulation markedly increased alveolar bone loss, periodontal pocket depth and the number of plaques. It also enhanced the inflammatory reaction. These results suggest that CS accelerated the ligature-induced pathological changes associated with periodontitis. Further analysis of the mechanisms involved showed that GR-α expression was significantly downregulated in periodontal tissues of the animals undergoing CS. Blocking GR-α signaling in lipopolysaccharide and corticosteroid-treated human periodontal ligament fibroblast cells in vitro significantly upregulated the expression of p-Akt (protein kinase B) and TLR4, promoted nuclear factor-κB activity and increased levels of IL-1β, IL-6 and IL-8. This research suggests that CS might accelerate the pathological progression of periodontitis by a GR-α signaling-mediated inflammatory response and that this may be a potential therapeutic target for the treatment of periodontal disease, particularly in patients with CS.

  10. Experimental Study of Residual Stresses in Metal Parts Obtained by Selective Laser Melting

    Science.gov (United States)

    Protasov, C. E.; Safronov, V. A.; Kotoban, D. V.; Gusarov, A. V.

    High local temperature gradients occur at additive manufacturing by selective laser melting of powder. This gives rise to undesirable residual stresses, deformations, and cracks. To understand how to control the formation of the residual stresses, a reliable method is necessary for measuring their distribution in the fabricated part. It is proposed to cut the part into thin plates and to reconstruct the residual stresses from the measured deformation of the plates. This method is tested on beams with square cross-section built from stainless steel. The beams were cut by electrical discharge machining and chemically etched. The obtained stress profile in vertical transversal direction slightly increases from the top to the bottom of the beam. This dependency is confirmed by numerical modeling. The measured stress profile agrees with the known results by other authors.

  11. Catch the Best: Novel Screening Strategy to Select Stress Protecting Agents for Crop Plants

    Directory of Open Access Journals (Sweden)

    Christin Zachow

    2013-11-01

    Full Text Available Climate change increases stress levels for crops and affects the economic and environmental aspects of agricultural management systems. The application of stress tolerance-mediating microorganisms is an auspicious strategy for improving crop protection, and as such, we developed a direct selection strategy to obtain cultivable microorganisms from promising bioresources using the bait plants, maize, oilseed rape, sorghum and sugar beet. Alpine mosses, lichens and primrose were selected as bioresources, as each is adapted to adverse environmental conditions. A 10% crop-specific selection was found for bait plant rhizosphere communities using cultivation-independent fingerprints, and their potential role as stress protecting agents (SPA was evaluated following the cultivation of captured bacteria. In addition to assays identifying phytopathogen antagonism and plant growth promotion capacities, our evaluation included those that test the ability to allocate nutrients. Moreover, we developed new assays to measure tolerance in diverse stress conditions. A score scheme was applied to select SPAs with desired properties, and three Pseudomonas species with pronounced antagonistic activity that showed elevated tolerance to desiccation and an improved seed germination rate were subsequently chosen. Screening for environmentally-conditioned and host-adapted microorganisms provides a novel tool for target-oriented exploitation of microbial bioresources for the management of ecofriendly crops facing biotic and abiotic stresses.

  12. Interactions of chronic lead exposure and intermittent stress: consequences for brain catecholamine systems and associated behaviors and HPA axis function.

    Science.gov (United States)

    Virgolini, Miriam B; Chen, Kevin; Weston, Doug D; Bauter, Mark R; Cory-Slechta, Deborah A

    2005-10-01

    Elevated lead (Pb) burden and high stress levels are co-occurring risk factors in low socioeconomic status (SES) children. Our previous work demonstrated that maternal Pb exposure can permanently alter hypothalamic-pituitary-adrenal (HPA) axis function and responsivity to stress challenges in offspring. The current study sought to determine the consequences of chronic Pb exposures initiated later in development combined with variable intermittent stress challenges. Male rats were exposed chronically from weaning to 0, 50, or 150 ppm Pb acetate drinking solutions (producing blood Pb levels of challenges including novelty, cold, and restraint, was measured as changes in Fixed Interval (FI) schedule-controlled behavior in a subset of rats within each group. FI performance was modified by novelty stress only in Pb-treated rats, whereas cold and restraint stress effects were comparable across groups. Novelty elevated corticosterone equivalently across groups, but cold stress markedly increased corticosterone only in Pb-treated groups. The pattern of Pb-induced changes in serotonin (5-HT) or its metabolite 5-HIAA in frontal cortex, nucleus accumbens, striatum, and hypothalamus resembled that observed for basal corticosterone levels indicating a relationship between these variables. In addition to suggesting the potential for HPA axis-mediated effects of Pb on the central nervous system, these findings also raise questions about whether single chemicals studied in isolation from other relevant risk factors can adequately identify neurotoxic hazards.

  13. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol

    Directory of Open Access Journals (Sweden)

    G. Morais-Silva

    2016-01-01

    Full Text Available Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol, but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30–35 g, 8-10 per group were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a “three-bottle choice” paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  14. Post-traumatic stress in patients with injury-related chronic pain participating in a multimodal pain rehabilitation program

    Directory of Open Access Journals (Sweden)

    Britt-Marie Stålnacke

    2010-03-01

    Full Text Available Britt-Marie Stålnacke, Anna ÖstmanDepartment of Community Medicine and Rehabilitation, Umeå University, SwedenAim: To investigate post-traumatic stress, pain intensity, depression, and anxiety in patients with injury-related chronic pain before and after participating in multimodal pain rehabilitation.Methods: Twenty-eight patients, 21 women and seven men, who participated in the multimodal rehabilitation programs (special whiplash program for whiplash injuries within 1.5 years after the trauma or ordinary program answered a set of questionnaires to assess post-traumatic stress (Impact of Event Scale [IES], pain intensity [Visual Analogue Scale (VAS], depression, and anxiety (Hospital Anxiety and Depression Scale [HAD] before and after the programs.Results: Both pain intensity and post-traumatic stress decreased significantly after the rehabilitation programs in comparison with before (VAS: 57.8 ± 21.6 vs. 67.5 ± 21.9; P = 0.009, IES total score 21.8 ± 13.2 vs. 29.5 ± 12.9; P < 0.001. Patients younger than 40 years reported a statistically higher level of post-traumatic stress compared with patients older than 40 years both before (P = 0.037 and after rehabilitation (P = 0.023. No statistically significant differences were found on the HAD scores.Conclusion: The multimodal rehabilitation programs were effective in reducing both pain intensity and post-traumatic stress. The experience of higher levels of post-traumatic stress in younger persons has to be taken into account when managing patients with injury-related chronic pain.Keywords: post-traumatic, stress disorder, chronic pain, whiplash injuries

  15. Concomitant stress potentiates the preference for, and consumption of, ethanol induced by chronic pre-exposure to ethanol.

    Science.gov (United States)

    Morais-Silva, G; Fernandes-Santos, J; Moreira-Silva, D; Marin, M T

    2016-01-01

    Ethanol abuse is linked to several acute and chronic injuries that can lead to health problems. Ethanol addiction is one of the most severe diseases linked to the abuse of this drug. Symptoms of ethanol addiction include compulsive substance intake and withdrawal syndrome. Stress exposure has an important role in addictive behavior for many drugs of abuse (including ethanol), but the consequences of stress and ethanol in the organism when these factors are concomitant results in a complex interaction. We investigated the effects of concomitant, chronic administration of ethanol and stress exposure on the withdrawal and consumption of, as well as the preference for, ethanol in mice. Male Swiss mice (30-35 g, 8-10 per group) were exposed to an ethanol liquid diet as the only source of food for 15 days. In the final 5 days, they were exposed to forced swimming stress. Twelve hours after removal of the ethanol liquid diet, animals were evaluated for ethanol withdrawal by measuring anxiety-related behaviors and locomotor activity. Twenty-four hours after evaluation of ethanol withdrawal, they were evaluated for voluntary consumption of ethanol in a "three-bottle choice" paradigm. Mice exposed to chronic consumption of ethanol had decreased locomotor activity during withdrawal. Contrary to our expectations, a concomitant forced swimming stress did not aggravate ethanol withdrawal. Nevertheless, simultaneous ethanol administration and stress exposure increased voluntary consumption of ethanol, mainly solutions containing high concentrations of ethanol. These results showed that stressful situations during ethanol intake may aggravate specific addiction-related behaviors.

  16. The North West Adelaide Health Study: detailed methods and baseline segmentation of a cohort for selected chronic diseases.

    Science.gov (United States)

    Grant, Janet F; Chittleborough, Catherine R; Taylor, Anne W; Dal Grande, Eleonora; Wilson, David H; Phillips, Patrick J; Adams, Robert J; Cheek, Julianne; Price, Kay; Gill, Tiffany; Ruffin, Richard E

    2006-04-12

    The North West Adelaide Health Study is a population-based biomedical cohort study investigating the prevalence of a number of chronic conditions and health-related risk factors along a continuum. This methodology may assist with evidence-based decisions for health policy makers and planners, and inform health professionals who are involved in chronic disease prevention and management, by providing a better description of people at risk of developing or already diagnosed with selected chronic conditions for more accurate targeting groups for health gain and improved health outcomes. Longitudinal data will provide information on progression of chronic conditions and allow description of those who move forward and back along the continuum over time. Detailed methods are provided regarding the random recruitment and examination of a representative sample of participants (n = 4060), including the rationale for various processes and valuable lessons learnt. Self-reported and biomedical data were obtained on risk factors (smoking, alcohol consumption, physical activity, family history, body mass index, blood pressure, cholesterol) and chronic conditions (asthma, chronic obstructive pulmonary disease, diabetes) to classify participants according to their status along a continuum. Segmenting this population sample along a continuum showed that 71.5% had at least one risk factor for developing asthma, chronic obstructive pulmonary disease or diabetes. Almost one-fifth (18.8%) had been previously diagnosed with at least one of these chronic conditions, and an additional 3.9% had at least one of these conditions but had not been diagnosed. This paper provides a novel opportunity to examine how a cohort study was born. It presents detailed methodology behind the selection, recruitment and examination of a cohort and how participants with selected chronic conditions can be segmented along a continuum that may assist with health promotion and health services planning.

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

    Directory of Open Access Journals (Sweden)

    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.

  18. The effect of oxidative stress in myocardial cell injury in mice exposed to chronic intermittent hypoxia

    Institute of Scientific and Technical Information of China (English)

    LIU Jian-nan; ZHANG Jie-xin; LIU gan; QIU Yan; YANG Di; YIN Guo-yong; ZHANG Xi-long

    2010-01-01

    Background Obstructive sleep apnea syndrome (OSAS) is an important risk factor for cardiovascular diseases. Chronic intermittent hypoxia (CIH) is considered to be one of the most important causes of cardiovascular diseases in OSA patients. This repeated hypoxia and reoxygenation cycle is similar to hypoxia-reperfusion injury, which initiates oxidative stress. In this study, we observed cardiocytes injury induced by CIH and the effect of N-acetylcysteine (NAC). Methods Thirty ICR mice were randomly assigned to 3 groups: control, CIH and NAC (CIH+NAC) groups. Malondialdehyde (MDA) and superoxide dismutase (SOD) of cardiocyte homogenates were measured. Serum lipids were measured by an instrument method. Serum cardiac troponin I (cTnl) was detected by enzyme-linked immunosorbent assays (ELISA). Myocardium pathological sections were observed.Results (1) The SOD activity and MDA concentration of cardiocyte homogenates in the CIH group were significantly higher than in other groups (P <0.005). The MDA concentration of the NAC group was lower than that of the control group (P <0.01). (2) The serum cTnl concentration of the CIH and NAC groups was significantly higher than that of the control group (P<0.01). (3) Serum triglyceride levels in the NAC group were lower than in the other groups (P<0.01), while there were no significant differences in low density lipoprotein and high density lipoprotein among the three groups. (4) The degeneration of myocardium, transverse striation blurred, and fabric effusion were observed in tissue sections in the CIH and NAC groups. However, normal tissue was found in the control group.Conclusion The oxidative stress induced by CIH can injure cardiocytes and the injury effect can be partially inhibited by NAC.

  19. Leukocyte telomere length in major depression: correlations with chronicity, inflammation and oxidative stress--preliminary findings.

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    Owen M Wolkowitz

    Full Text Available BACKGROUND: Depression is associated with an unusually high rate of aging-related illnesses and early mortality. One aspect of "accelerated aging" in depression may be shortened leukocyte telomeres. When telomeres critically shorten, as often occurs with repeated mitoses or in response to oxidation and inflammation, cells may die. Indeed, leukocyte telomere shortening predicts early mortality and medical illnesses in non-depressed populations. We sought to determine if leukocyte telomeres are shortened in Major Depressive Disorder (MDD, whether this is a function of lifetime depression exposure and whether this is related to putative mediators, oxidation and inflammation. METHODOLOGY: Leukocyte telomere length was compared between 18 unmedicated MDD subjects and 17 controls and was correlated with lifetime depression chronicity and peripheral markers of oxidation (F2-isoprostane/Vitamin C ratio and inflammation (IL-6. Analyses were controlled for age and sex. PRINCIPAL FINDINGS: The depressed group, as a whole, did not differ from the controls in telomere length. However, telomere length was significantly inversely correlated with lifetime depression exposure, even after controlling for age (p<0.05. Average telomere length in the depressed subjects who were above the median of lifetime depression exposure (≥9.2 years' cumulative duration was 281 base pairs shorter than that in controls (p<0.05, corresponding to approximately seven years of "accelerated cell aging." Telomere length was inversely correlated with oxidative stress in the depressed subjects (p<0.01 and in the controls (p<0.05 and with inflammation in the depressed subjects (p<0.05. CONCLUSIONS: These preliminary data indicate that accelerated aging at the level of leukocyte telomeres is proportional to lifetime exposure to MDD. This might be related to cumulative exposure to oxidative stress and inflammation in MDD. This suggest that telomere shortening does not antedate depression

  20. Effects of heart rate variability biofeedback in subjects with stress-related chronic neck pain: a pilot study.

    Science.gov (United States)

    Hallman, David M; Olsson, Erik M G; von Schéele, Bo; Melin, Lennart; Lyskov, Eugene

    2011-06-01

    Recent studies focusing on autonomic nervous system (ANS) dysfunctions, together with theoretical pathophysiological models of musculoskeletal disorders, indicate the involvement of ANS regulation in development and maintenance of chronic muscle pain. Research has demonstrated the effectiveness of heart rate variability (HRV) biofeedback (BF) in increasing HRV and reducing the symptoms of different disorders characterized by ANS aberration. The study investigated the effects of resonance frequency HRV BF on autonomic regulation and perceived health, pain, stress and disability in 24 subjects with stress-related chronic neck-shoulder pain. Twelve subjects participated in 10 weekly sessions of resonant HRV BF and were compared to a control group. Subjective reports and HRV measures during relaxation and in response to a standardized stress protocol were assessed for both groups pre- and post-intervention. Group × time interactions revealed a significantly stronger increase over time in perceived health (SF-36) for the treatment group, including vitality, bodily pain and social functioning. Interactions were also seen for HRV during relaxation and reactivity to stress. The present pilot study indicates improvement in perceived health over a 10 week intervention with HRV-biofeedback in subjects with chronic neck-pain. Increased resting HRV as well as enhanced reactivity to hand grip and cold pressor tests might reflect beneficial effects on ANS regulation, and suggest that this intervention protocol is suitable for a larger controlled trial.

  1. Cotinine reduces depressive-like behavior, working memory deficits, and synaptic loss associated with chronic stress in mice.

    Science.gov (United States)

    Grizzell, J Alex; Iarkov, Alexandre; Holmes, Rosalee; Mori, Takahashi; Echeverria, Valentina

    2014-07-15

    Chronic stress underlies and/or exacerbates many psychiatric conditions and often results in memory impairment as well as depressive symptoms. Such afflicted individuals use tobacco more than the general population and this has been suggested as a form of self-medication. Cotinine, the predominant metabolite of nicotine, may underlie such behavior as it has been shown to ameliorate anxiety and memory loss in animal models. In this study, we sought to investigate the effects of cotinine on working memory and depressive-like behavior in mice subjected to prolonged restraint. Cotinine-treated mice displayed better performance than vehicle-treated cohorts on the working memory task, the radial arm water maze test. In addition, with or without chronic stress exposure, cotinine-treated mice engaged in fewer depressive-like behaviors as assessed using the tail suspension and Porsolt's forced swim tests. These antidepressant and nootropic effects of cotinine were associated with an increase in the synaptophysin expression, a commonly used marker of synaptic density, in the hippocampus as well as the prefrontal and entorhinal cortices of restrained mice. The beneficial effects of cotinine in preventing various consequences of chronic stress were underscored by the inhibition of the glycogen synthase kinase 3 β in the hippocampus and prefrontal cortex. Taken together, our results show for the first time that cotinine reduces the negative effects of stress on mood, memory, and the synapse.

  2. Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice

    OpenAIRE

    Bahi, Amine; Dreyer, Jean-Luc

    2014-01-01

    Objective: Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP.Methods: Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were s...

  3. Chronic chemotherapeutic stress promotes evolution of stemness and WNT/beta-catenin signaling in colorectal cancer cells: implications for clinical use of WNT-signaling inhibitors

    Science.gov (United States)

    Ayadi, Meriam; Bouygues, Anaïs; Ouaret, Djamila; Ferrand, Nathalie; Chouaib, Salem; Thiery, Jean-Paul; Muchardt, Christian; Sabbah, Michèle; Larsen, Annette K

    2015-01-01

    Most solid tumors contain a subfraction of cells with stem/progenitor cell features. Stem cells are naturally chemoresistant suggesting that chronic chemotherapeutic stress may select for cells with increased “stemness”. We carried out a comprehensive molecular and functional analysis of six independently selected colorectal cancer (CRC) cell lines with acquired resistance to three different chemotherapeutic agents derived from two distinct parental cell lines. Chronic drug exposure resulted in complex alterations of stem cell markers that could be classified into three categories: 1) one cell line, HT-29/5-FU, showed increased “stemness” and WNT-signaling, 2) three cell lines showed decreased expression of stem cell markers, decreased aldehyde dehydrogenase activity, attenuated WNT-signaling and lost the capacity to form colonospheres and 3) two cell lines displayed prominent expression of ABC transporters with a heterogeneous response for stem cell markers. While WNT-signaling could be attenuated in the HT-29/5-FU cells by the WNT-signaling inhibitors ICG-001 and PKF-118, this was not accompanied by any selective growth inhibitory effect suggesting that the cytotoxic activity of these compounds is not directly linked to WNT-signaling inhibition. We conclude that classical WNT-signaling inhibitors have toxic off-target activities that need to be addressed for clinical development. PMID:26041882

  4. Impaired hippocampal neuroligin-2 function by chronic stress or synthetic peptide treatment is linked to social deficits and increased aggression.

    Science.gov (United States)

    van der Kooij, Michael A; Fantin, Martina; Kraev, Igor; Korshunova, Irina; Grosse, Jocelyn; Zanoletti, Olivia; Guirado, Ramon; Garcia-Mompó, Clara; Nacher, Juan; Stewart, Michael G; Berezin, Vladimir; Sandi, Carmen

    2014-04-01

    Neuroligins (NLGNs) are cell adhesion molecules that are important for proper synaptic formation and functioning, and are critical regulators of the balance between neural excitation/inhibition (E/I). Mutations in NLGNs have been linked to psychiatric disorders in humans involving social dysfunction and are related to similar abnormalities in animal models. Chronic stress increases the likelihood for affective disorders and has been shown to induce changes in neural structure and function in different brain regions, with the hippocampus being highly vulnerable to stress. Previous studies have shown evidence of chronic stress-induced changes in the neural E/I balance in the hippocampus. Therefore, we hypothesized that chronic restraint stress would lead to reduced hippocampal NLGN-2 levels, in association with alterations in social behavior. We found that rats submitted to chronic restraint stress in adulthood display reduced sociability and increased aggression. This occurs along with a reduction of NLGN-2, but not NLGN-1 expression (as shown with western blot, immunohistochemistry, and electron microscopy analyses), throughout the hippocampus and detectable in different layers of the CA1, CA3, and DG subfields. Furthermore, using synthetic peptides that comprise sequences in either NLGN-1 (neurolide-1) or NLGN-2 (neurolide-2) involved in the interaction with their presynaptic partner neurexin (NRXN)-1, intra-hippocampal administration of neurolide-2 led also to reduced sociability and increased aggression. These results highlight hippocampal NLGN-2 as a key molecular substrate regulating social behaviors and underscore NLGNs as promising targets for the development of novel drugs for the treatment of dysfunctional social behaviors.

  5. Zinc and imipramine reverse the depression-like behavior in mice induced by chronic restraint stress.

    Science.gov (United States)

    Ding, Qin; Li, Hongxia; Tian, Xue; Shen, Zhilei; Wang, Xiaoli; Mo, Fengfeng; Huang, Junlong; Shen, Hui

    2016-06-01

    Depression is a common psychopathological disorders. Studies of depression have indicated that zinc play a role in the depression pathophysiology and treatment. In present study, we examined the effects of zinc and imipramine supplement alone or combination of zinc and imipramine in mice induced by chronic restraint stress (CRS). Moreover, the possible roles of zinc receptor (G protein-coupled receptor 39, GPR39)-related pathway was investigated. Decreased weight and increased corticosterone (CORT) were observed after 3 weeks CRS exposure. It was shown that CRS induced lower serum zinc, higher hippocampal zinc, increased immobility time in tail suspension test and decreased movement distance in spontaneous activity test, which could be normalized by zinc (30 mg/kg) and imipramine (20 mg/kg) supplement alone and combination of zinc (15 mg/kg) and imipramine (5 mg/kg) for 3 weeks after CRS exposure. Moreover, the changes in mRNA expressions of GPR39, cAMP-response element binding protein (CREB), brain-derived neurotropic factor (BDNF) and n-methytl-d-aspartate receptors (NMDAR) could be reversed by the same treatment mentioned above. These results suggested that zinc dyshomeostasis in serum and hippocampus and depression-like behavior in CRS exposure animals observed in present study could be normalized by zinc and imipramine. The combination of zinc and imipramine in low dose has synergetic effects. The possible mechanism might be correlated to GPR39 receptor-related pathway.

  6. 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.

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

    Science.gov (United States)

    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.

  8. A twin study of posttraumatic stress disorder symptoms and chronic widespread pain.

    Science.gov (United States)

    Arguelles, Lester M; Afari, Niloofar; Buchwald, Dedra S; Clauw, Daniel J; Furner, Sylvia; Goldberg, Jack

    2006-09-01

    Previous studies of the association between posttraumatic stress disorder (PTSD) and chronic widespread pain (CWP) or fibromyalgia have not examined the role of familial or genetic factors. The goals of this study were to determine if symptoms of PTSD are related to CWP in a genetically informative community-based sample of twin pairs, and if so, to ascertain if the association is due to familial or genetic factors. Data were obtained from the University of Washington Twin Registry, which contains 1042 monozygotic and 828 dizygotic twin pairs. To assess the symptoms of PTSD, we used questions from the Impact of Events Scale (IES). IES scores were partitioned into terciles. CWP was defined as pain located in 3 body regions lasting at least 1 week during the past 3 months. Random-effects regression models, adjusted for demographic features and depression, examined the relationship between IES and CWP. IES scores were strongly associated with CWP (P<0.0001). Compared to those in the lowest IES tercile, twins in the highest tercile were 3.5 times more likely to report CWP. Although IES scores were associated with CWP more strongly among dizygotic than among monozygotic twins, this difference was not significant. Our findings suggest that PTSD symptoms, as measured by IES, are strongly linked to CWP, but this association is not explained by a common familial or genetic vulnerability to both conditions. Future research is needed to understand the temporal association of PTSD and CWP, as well as the physiological underpinnings of this relationship.

  9. Chronic stress-like syndrome as a consequence of medial site subthalamic stimulation in Parkinson's disease.

    Science.gov (United States)

    Růžička, Filip; Jech, Robert; Nováková, Lucie; Urgošík, Dušan; Bezdíček, Ondřej; Vymazal, Josef; Růžička, Evžen

    2015-02-01

    Considering the functional organization of the subthalamic nucleus (STN), we hypothesized that subthalamic deep brain stimulation (STN-DBS) in Parkinson's disease might have a differential impact on the hypothalamic-pituitary-adrenal axis in relation to the position of active stimulating contact within the STN. In addition, we searched for any STN-DBS-related morning plasma cortisol changes in association with postoperative anxiety and weight gain. A plasma cortisol measurement was performed on the day of initiation of bilateral STN-DBS and repeated after 1 and 17 months in twenty patients with advanced Parkinson's disease. The body weight change and anxiety scores following the implantation were assessed as well. The electrode positions in the STN were determined on T1-weighted magnetic resonance images. After initiation of stimulation, cortisol levels significantly decreased and the cortisol changes after 1 and 17 months strongly correlated with the position of active contact in the subthalamic area. Patients with at least one contact located more medially in the STN experienced a significantly greater decrease of cortisol than those with one or both active contacts more laterally. Furthermore, the lower cortisol levels were strongly associated with higher trait anxiety and weight gain. These changes mimicked the effects of chronic stress and suggest the disturbing impact of STN-DBS on limbic and motivational systems.

  10. Epistasis and maternal effects in experimental adaptation to chronic nutritional stress in Drosophila.

    Science.gov (United States)

    Vijendravarma, R K; Kawecki, T J

    2013-12-01

    Based on ecological and metabolic arguments, some authors predict that adaptation to novel, harsh environments should involve alleles showing negative (diminishing return) epistasis and/or that it should be mediated in part by evolution of maternal effects. Although the first prediction has been supported in microbes, there has been little experimental support for either prediction in multicellular eukaryotes. Here we use a line-cross design to study the genetic architecture of adaptation to chronic larval malnutrition in a population of Drosophila melanogaster that evolved on an extremely nutrient-poor larval food for 84 generations. We assayed three fitness-related traits (developmental rate, adult female weight and egg-to-adult viability) under the malnutrition conditions in 14 crosses between this selected population and a nonadapted control population originally derived from the same base population. All traits showed a pattern of negative epistasis between alleles improving performance under malnutrition. Furthermore, evolutionary changes in maternal traits accounted for half of the 68% increase in viability and for the whole of 8% reduction in adult female body weight in the selected population (relative to unselected controls). These results thus support both of the above predictions and point to the importance of nonadditive effects in adaptive microevolution.

  11. Cortisol-dependent stress effects on cell distribution in healthy individuals and individuals suffering from chronic adrenal insufficiency.

    Science.gov (United States)

    Geiger, Ashley M; Pitts, Kenneth P; Feldkamp, Joachim; Kirschbaum, Clemens; Wolf, Jutta M

    2015-11-01

    Chronic adrenal insufficiency (CAI) is characterized by a lack of glucocorticoid and mineralocorticoid production due to destroyed adrenal cortex cells. However, elevated cortisol secretion is thought to be a central part in a well-orchestrated immune response to stress. This raises the question to what extent lack of cortisol in CAI affects stress-related changes in immune processes. To address this question, 28 CAI patients (20 females) and 18 healthy individuals (11 females) (age: 44.3 ± 8.4 years) were exposed to a psychosocial stress test (Trier Social Stress Test: TSST). Half the patients received a 0.03 mg/kg body weight injection of hydrocortisone (HC) post-TSST to mimic a healthy cortisol stress response. Catecholamines and immune cell composition were assessed in peripheral blood and free cortisol measured in saliva collected before and repeatedly after TSST. CAI patients showed norepinephrine (NE) stress responses similar to healthy participants, however, epinephrine (E) as well as cortisol levels were significantly lower. HC treatment post-TSST resulted in cortisol increases comparable to those observed in healthy participants (interaction effects--NE: F=1.05, p=.41; E: F=2.56, p=.045; cortisol: F=13.28, pcortisol's central involvement in post-stress lymphocyte migration from blood into immune-relevant body compartments. As such, future studies should investigate whether psychosocial stress exposure may put CAI patients at an increased health risk due to attenuated immune responses to pathogens.

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

    Directory of Open Access Journals (Sweden)

    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

  13. ACTIVATION MECHANISMS OF GUT-ASSOCIATED LYMPHOID TISSUE UNDER CHRONIC SOCIAL STRESS CONDITIONS

    Directory of Open Access Journals (Sweden)

    A. M. Kamyshnyi

    2015-01-01

    Full Text Available Stress-induced immune disregulation is a risk factor of autoimmune and inflammatory diseases, but, so far, the mechanisms for this effect are not fully known. Expression levels of specific mRNAs were assessed in gut-associated lymphoid tissue (GALT from Wistar rats subjected to chronic social stress (CSS. Gene expression was evaluated for NR3C1, Adrβ2, as well as IL-1β, IL-17α pro-inflammatory cytokines, and Nlrp, an inflammasome gene. Under the CSS conditions, we have shown altered distribution of RORγt +, FoxP3+, LMP2+, XBP1+ lymphocytes in GALT.The experiments were carried out with female Wistar rats aged 5–6 months. Specific mRNA expression for the target genes was determined by means of real-time PCR performed in a CFX96™ thermocycler («BioRadLaboratories, Inc»,USA. Relative levels of a target gene expression were quantified by the ΔΔCt method, being compared with rat GAPDH reference gene expression. Statistical analysis was performed with available «BioRad СFX Manager 3.1» software. Specific monoclonal rat antibodes were used for detection of immunopositive lymphocytes by means of indirect immunofluorescence technique.CSS development leads to decreased levels of mRNA expression for Nr3c1 and Adrβ2-genes in the GALT cells, being accompanied with unidirectional changes, i.e., increased transcription of pro-inflammatory cytokine mRNAs (IL-1β, IL-17α and Nlrp3-inflammasome genes. These changes are accompanied by decreased FoxP3+/RORγt + cell ratio and predominant Th17 differentiation accompanied by suppressor failure. In addition, CSS development was characterized by unidirectional tendency for increasing total number of LMP2+ lymphocytes and reduced ХВР1+ cell population density in lymphoid structures of rat ileum.The events observed in GALT cell populations under CSS conditions are opposing classical paradigm of the stress response. The CSS-associated effects do not promote immunosuppression, however, are able to cause

  14. Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

    Science.gov (United States)

    Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

    2015-02-01

    Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

  15. Pancreatoduodenectomy for chronic pancreatitis: anatomic selection criteria and subsequent long-term outcome analysis.

    Science.gov (United States)

    Traverso, L W; Kozarek, R A

    1997-01-01

    OBJECTIVE: The authors sought to provide a framework through outcome analysis to evaluate operations directed toward the intractable abdominal pain of severe chronic pancreatitis centered in the pancreatic head. Pancreatoduodenectomy (PD) was used as an example. SUMMARY BACKGROUND DATA: Head resection for severe chronic pancreatitis is the treatment of choice for a ductal system in the head obliterated by severe disease when associated with intractable abdominal pain. To evaluate the effectiveness of promising head resection substitutes for PD, a framework is necessary to provide a reference standard (i.e., an outcome analysis) of PD. METHODS: Inclusion criteria were severe chronic pancreatitis centered in the pancreatic head, intractable abdominal pain, and a main pancreatic duct obstruction or stricture resulting in absent drainage into the duodenum from the uncinate process and adjacent pancreatic head areas or the entire gland. Since 1986, 57 consecutive cases with these criteria underwent PD (47 head only and 10 total pancreatectomy). Clinical and anatomic predictor variables were derived from the history, imaging studies, and pathologic examination. These variables then were tested for association with the following outcome events gathered during annual follow-up: pain relief, onset of diabetes, body weight maintenance, and peptic ulceration. RESULTS: Operative mortality was zero. In 57 patients with a mean follow-up of 42 months, the 5-year outcome event for survival was 93% and the onset of diabetes was 32%. All new cases of diabetes occurred more than 1 year after resection. In 43 cases > or =1 year postoperative with a mean follow-up of 55 months, all patients indicated significant pain relief and 76% were pain free. Pain relief was more common in patients with diabetes or in those patients with a pancreatic duct disruption. Death was more common in patients with diabetes. Weight maintenance was more common if preoperatively severe ductal changes were not

  16. Xiaoyaosan Decoction Regulates Changes in Neuropeptide Y and Leptin Receptor in the Rat Arcuate Nucleus after Chronic Immobilization Stress

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    Shao-Xian Wang

    2012-01-01

    Full Text Available The arcuate nucleus (ARC in the basal of hypothalamus plays an important role in appetite regulation and energy balance. We sought to investigate the central neuroendocrine mechanism of appetite decrease and weight loss under chronic stress by observing the regulatory effects of Xiaoyaosan decoction in the expression of leptin receptor (ob-R and neuropeptide Y (NPY in the ARC. Our results showed that bodyweight and food intake of rats in the 21-day stress group increased slower than those of the normal group. Higher contents of Leptin and ob-R were noted in the 21-day stress group compared with control rats, while NPY expression was not statistically different. Xiaoyaosan powder can significantly downregulate the contents of leptin and ob-R in the hypothalamus of stressed rats. These findings suggest that increase of ob-R expression in the ARC is possibly one key central neuroendocrine change for the somatic discomfort. Weight loss and decreased food intake in rats caused by the binding of leptin to ob-R in hypothalamus do not appear to utilize the NPY pathway. This study also suggests that ob-R in the ARC may act as the target of Xiaoyaosan in regulating the symptoms such as appetite decrease and bodyweight loss under chronic stress.

  17. Revealing stiffening and brittling of chronic myelogenous leukemia hematopoietic primary cells through their temporal response to shear stress

    Science.gov (United States)

    Laperrousaz, B.; Berguiga, L.; Nicolini, F. E.; Martinez-Torres, C.; Arneodo, A.; Maguer Satta, V.; Argoul, F.

    2016-06-01

    Cancer cell transformation is often accompanied by a modification of their viscoelastic properties. When capturing the stress-to-strain response of primary chronic myelogenous leukemia (CML) cells, from two data sets of CD34+ hematopoietic cells isolated from healthy and leukemic bone marrows, we show that the mean shear relaxation modulus increases upon cancer transformation. This stiffening of the cells comes along with local rupture events, detected as reinforced sharp local maxima of this modulus, suggesting that these cancer cells respond to a local mechanical stress by a cascade of local brittle failure events.

  18. Metabolomic analysis of the selection response of Drosophila melanogaster to environmental stress

    DEFF Research Database (Denmark)

    Malmendal, Anders; Sørensen, Jesper Givskov; Overgaard, Johannes

    2013-01-01

    We investigated the global metabolite response to artificial selection for tolerance to stressful conditions such as cold, heat, starvation, and desiccation, and for longevity in Drosophila melanogaster. Our findings were compared to data from other levels of biological organization, including gene...

  19. Evaluation of the protective effects of tocotrienol-rich fraction from palm oil on the dentate gyrus following chronic restraint stress in rats

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    Saiful Bhari Talip

    2013-06-01

    Full Text Available Exposure to chronic restraint stress has been shown to cause a number of morphological changes in the hippocampal formation of rats. Tocotrienol, an isoform of vitamin E, exhibits numerous health benefits, different from those of tocopherol. Recent studies have demonstrated that tocotrienol prevents stress-induced changes in the gastric mucosa, thus indicating that it may also protect other organs such as the brain from the damaging effects of stress. Therefore, the aim of the present study was to investigate the protective effect of tocotrienol-rich fraction (TRF extracted from palm oil on the dentate gyrus of rats following exposure to chronic restraint stress. Thirty-six male Sprague Dawley rats were divided into four groups: control, stress, tocotrienol and combination of stress and tocotrienol. Animals were stressed by restraining them for 5 hours every day for 21 consecutive days. TRF was administered via oral gavage at a dose of 200 mg/kg body weight. Our results showed that the plasma corticosterone level was significantly increased in response to stress, compared to the control. The results confirmed previous findings that chronic restraint stress suppresses cellular proliferation and reduces granule cell number in the dentate gyrus. However, TRF supplementation failed to prevent or minimize these stress-induced changes. Therefore, we conclude that TRF at the current dosage is not effective in preventing the morphological changes in the dentate gyrus induced by chronic restraint stress.

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

    Institute of Scientific and Technical Information of China (English)

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

    2011-01-01

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