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

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Popović Nataša

2010-01-01

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

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

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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.

Effect of chronic restraint stress on inhibitory gating in the auditory cortex of rats.

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Ma, Lanlan; Li, Wai; Li, Sibin; Wang, Xuejiao; Qin, Ling

2017-05-01

A fundamental adaptive mechanism of auditory function is inhibitory gating (IG), which refers to the attenuation of neural responses to repeated sound stimuli. IG is drastically impaired in individuals with emotional and cognitive impairments (i.e. posttraumatic stress disorder). The objective of this study was to test whether chronic stress impairs the IG of the auditory cortex (AC). We used the standard two-tone stimulus paradigm and examined the parametric qualities of IG in the AC of rats by recording the electrophysiological signals of a single-unit and local field potential (LFP) simultaneously. The main results of this study were that most of the AC neurons showed a weaker response to the second tone than to the first tone, reflecting an IG of the repeated input. A fast negative wave of LFP showed consistent IG across the sampled AC sites, whereas a slow positive wave of LFP had less IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level, due to the increase in response to the second tone. This study provided new evidence that chronic stress disrupts the physiological function of the AC. Lay Summary The effects of chronic stress on IG were investigated by recording both, single-unit spike and LFP activities, in the AC of rats. In normal rats, most of the single-unit and N25 LFP activities in the AC showed an IG effect. IG was diminished following chronic restraint stress at both, the single-unit and LFP level.

A neuroplasticity hypothesis of chronic stress in the basolateral amygdala.

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Boyle, Lara M

2013-06-01

Chronic stress plays a role in the etiology of several affective and anxiety-related disorders. Despite this, its mechanistic effects on the brain are still unclear. Of particular interest is the effect of chronic stress on the amygdala, which plays a key role in the regulation of emotional responses and memory consolidation. This review proposes a neuroplasticity model for the effects of chronic stress in this region, emphasizing the roles of glutamate and BDNF signaling. This model provides a review of recent discoveries of the effects of chronic stress in the amygdala and reveals pathways for future research.

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

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.

Effects of fluoxetine on changes of pain sensitivity in chronic stress model rats.

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Lian, Yan-Na; Chang, Jin-Long; Lu, Qi; Wang, Yi; Zhang, Ying; Zhang, Feng-Min

2017-06-09

Exposure to stress could facilitate or inhibit pain responses (stress-induced hyperalgesia or hypoalgesia, respectively). Fluoxetine is a selective serotonin (5-HT) reuptake inhibitor antidepressant. There have been contradictory reports on whether fluoxetine produces antinociceptive effects. The purpose of this study was to elucidate changes in pain sensitivity after chronic stress exposure, and the effects of fluoxetine on these changes. We measured thermal, mechanical, and formalin-induced acute and inflammatory pain by using the tail-flick, von Frey, and formalin tests respectively. The results showed that rats exposed to chronic stress exhibited thermal and formalin-induced acute and inflammatory hypoalgesia and transient mechanical hyperalgesia. Furthermore, fluoxetine promoted hypoalgesia in thermal and inflammatory pain and induced mechanical hyperalgesia. Our results indicate that the 5-HT system could be involved in hypoalgesia of thermal and inflammatory pain and induce transient mechanical hyperalgesia after stress exposure. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

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.

Adverse effect of combination of chronic psychosocial stress and high fat diet on hippocampus-dependent memory in rats.

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

2009-12-01

The combined effects of high fat diet (HFD) and chronic stress on the hippocampus-dependent spatial learning and memory were studied in rats using the radial arm water maze (RAWM). Chronic psychosocial stress and/or HFD were simultaneously administered for 3 months to young adult male Wister rats. In the RAWM, rats were subjected to 12 learning trials as well as short-term and long-term memory tests. This procedure was applied on a daily basis until the animal reaches days to criterion (DTC) in the 12th learning trial and in memory tests. DTC is the number of days that the animal takes to make zero error in two consecutive days. Groups were compared based on the number of errors per trial or test as well as on the DTC. Chronic stress, HFD and chronic stress/HFD animal groups showed impaired learning as indicated by committing significantly (Pchronic stress, HFD and chronic stress/HFD groups showed significantly impaired performance compared to control group. Additionally, the stress/HFD was the only group that showed significantly impaired performance in memory tests on the 5th training day, suggesting more severe memory impairment in that group. Furthermore, DTC value for above groups indicated that chronic stress or HFD, alone, resulted in a mild impairment of spatial memory, but the combination of chronic stress and HFD resulted in a more severe and long-lasting memory impairment. The data indicated that the combination of stress and HFD produced more deleterious effects on hippocampal cognitive function than either chronic stress or HFD alone.

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

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

Chronic stress and neural function: accounting for sex and age.

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Luine, V N; Beck, K D; Bowman, R E; Frankfurt, M; Maclusky, N J

2007-10-01

Cognitive responses to stress follow the temporally dependent pattern originally established by Selye (1) wherein short-term stressors elicit adaptive responses whereas continued stress (chronic) results in maladaptive changes--deleterious effects on physiological systems and impaired cognition. However, this pattern for cognitive effects appears to apply to only half the population (males) and, more specifically, to young, adult males. Females show different cognitive responses to stress. In contrast to impaired cognition in males after chronic stress, female rodents show enhanced performance on the same memory tasks after the same stress. Not only cognition, but anxiety, shows sex-dependent changes following chronic stress--stress is anxiolytic in males and anxiogenic in females. Moreover, behavioral responses to chronic stress are different in developing as well as aging subjects (both sexes) as compared to adults. In aged rats, chronic stress enhances recognition memory in both sexes, does not alter spatial memory, and anxiety effects are opposite to young adults. When pregnant dams are exposed to chronic stress, at adulthood the offspring display yet different consequences of stress on anxiety and cognition, and, in contrast to adulthood when the behavioral effects of stress are reversible, prenatal stress effects appear enduring. Changing levels of estradiol in the sexes over the lifespan appear to contribute to the differences in response to stress. Thus, theories of stress dependent modulations in CNS function--developed solely in male models, focused on peripheral physiological processes and tested in adults--may require revision when applied to a more diverse population (age- and sex-wise) at least in relation to the neural functions of cognition and anxiety. Moreover, these results suggest that other stressors and neural functions should be investigated to determine whether age, sex and gonadal hormones also have an impact.

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 female offspring of pregnant rats (Mol:WIST) exposed to chronic mild stress (CMS) during gestational days (GD) 9-20, or 1500 ppm toluene, 6 h/day during gestational days 7-20, or a combination of the two. Prenatal CMS was associated with decreased thymic weight and increased auditory startle response....... The corticosterone response to restraint seemed modified by prenatal exposure to toluene. Lactational body weight was decreased in offsprings subjected to CMS, primarily due to effects in the combined exposure group. Cognitive function was investigated in the Morris water maze, and some indications of improved...

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

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Eli Puterman

2010-05-01

Full Text Available 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.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.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.

Food cravings mediate the relationship between chronic stress and body mass index.

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Chao, Ariana; Grilo, Carlos M; White, Marney A; Sinha, Rajita

2015-06-01

This study examined the relationships between chronic stress, food cravings, and body mass index. A community-based sample of adults (N = 619) completed a comprehensive assessment battery and heights and weights were measured. Chronic stress had a significant direct effect on food cravings, and food cravings had a significant direct effect on body mass index. The total effect of chronic stress on body mass index was significant. Food cravings partially mediated the relationship between chronic stress and body mass index. These findings are consistent with research that chronic stress may potentiate motivation for rewarding substances and behaviors and indicate that high food cravings may contribute to stress-related weight gain. © The Author(s) 2015.

Blunted stress reactivity in chronic cannabis users.

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Cuttler, Carrie; Spradlin, Alexander; Nusbaum, Amy T; Whitney, Paul; Hinson, John M; McLaughlin, Ryan J

2017-08-01

One of the most commonly cited reasons for chronic cannabis use is to cope with stress. Consistent with this, cannabis users have shown reduced emotional arousal and dampened stress reactivity in response to negative imagery. To our knowledge, the present study represents the first to examine the effects of an acute stress manipulation on subjective stress and salivary cortisol in chronic cannabis users compared to non-users. Forty cannabis users and 42 non-users were randomly assigned to complete either the stress or no stress conditions of the Maastricht Acute Stress Test (MAST). The stress condition of the MAST manipulates both physiological (placing hand in ice bath) and psychosocial stress (performing math under conditions of social evaluation). Participants gave baseline subjective stress ratings before, during, and after the stress manipulation. Cortisol was measured from saliva samples obtained before and after the stress manipulation. Further, cannabis cravings and symptoms of withdrawal were measured. Subjective stress ratings and cortisol levels were significantly higher in non-users in the stress condition relative to non-users in the no stress condition. In contrast, cannabis users demonstrated blunted stress reactivity; specifically, they showed no increase in cortisol and a significantly smaller increase in subjective stress ratings. The stress manipulation had no impact on cannabis users' self-reported cravings or withdrawal symptoms. Chronic cannabis use is associated with blunted stress reactivity. Future research is needed to determine whether this helps to confer resiliency or vulnerability to stress-related psychopathology as well as the mechanisms underlying this effect.

Beneficial effects of benzodiazepine diazepam on chronic stress-induced impairment of hippocampal structural plasticity and depression-like behavior in mice.

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Zhao, Yunan; Wang, Zhongli; Dai, Jianguo; Chen, Lin; Huang, Yufang; Zhan, Zhen

2012-03-17

Whether benzodiazepines (BZDs) have beneficial effects on the progress of chronic stress-induced impairment of hippocampal structural plasticity and major depression is uncertain. The present study designed four preclinical experiments to determine the effects of BZDs using chronic unpredictable stress model. In Experiment 1, several time course studies on behavior and hippocampus response to stress were conducted using the forced swim and tail suspension tests (FST and TST) as well as hippocampal structural plasticity markers. Chronic stress induced depression-like behavior in the FST and TST as well as decreased hippocampal structural plasticity that returned to normal within 3 wk. In Experiment 2, mice received p.o. administration of three diazepam dosages prior to each variate stress session for 4 wk. This treatment significantly antagonized the elevation of stress-induced corticosterone levels. Only low- (0.5mg/kg) and medium-dose (1mg/kg) diazepam blocked the detrimental effects of chronic stress. In Experiment 3, after 7 wk of stress sessions, daily p.o. diazepam administration during 1 wk recovery phase dose-dependently accelerated the recovery of stressed mice. In Experiment 4, 1 wk diazepam administration to control mice enhanced significantly hippocampal structural plasticity and induced an antidepressant-like behavioral effect, whereas 4 wk diazepam administration produced opposite effects. Hence, diazepam can slow the progress of chronic stress-induced detrimental consequences by normalizing glucocorticoid hormones. Considering the adverse effect of long-term diazepam administration on hippocampal plasticity, the preventive effects of diazepam may depend on the proper dose. Short-term diazepam treatment enhances hippocampal structural plasticity and is beneficial to recovery following chronic stress. Copyright © 2011 Elsevier B.V. All rights reserved.

Oxidative stress adaptation with acute, chronic, and repeated stress.

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

2013-02-01

Oxidative stress adaptation, or hormesis, is an important mechanism by which cells and organisms respond to, and cope with, environmental and physiological shifts in the level of oxidative stress. Most studies of oxidative stress adaption have been limited to adaptation induced by acute stress. In contrast, many if not most environmental and physiological stresses are either repeated or chronic. In this study we find that both cultured mammalian cells and the fruit fly Drosophila melanogaster are capable of adapting to chronic or repeated stress by upregulating protective systems, such as their proteasomal proteolytic capacity to remove oxidized proteins. Repeated stress adaptation resulted in significant extension of adaptive responses. Repeated stresses must occur at sufficiently long intervals, however (12-h or more for MEF cells and 7 days or more for flies), for adaptation to be successful, and the levels of both repeated and chronic stress must be lower than is optimal for adaptation to acute stress. Regrettably, regimens of adaptation to both repeated and chronic stress that were successful for short-term survival in Drosophila nevertheless also caused significant reductions in life span for the flies. Thus, although both repeated and chronic stress can be tolerated, they may result in a shorter life. Copyright © 2012 Elsevier Inc. All rights reserved.

Curcumin reverses the effects of chronic stress on behavior, the HPA axis, BDNF expression and phosphorylation of CREB.

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Xu, Ying; Ku, Baoshan; Tie, Lu; Yao, Haiyan; Jiang, Wengao; Ma, Xing; Li, Xuejun

2006-11-29

Curcuma longa is a major constituent of the traditional Chinese medicine Xiaoyao-san, which has been used to effectively manage stress and depression-related disorders in China. Curcumin is the active component of curcuma longa, and its antidepressant effects were described in our prior studies in mouse models of behavioral despair. We hypothesized that curcumin may also alleviate stress-induced depressive-like behaviors and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Thus in present study we assessed whether curcumin treatment (2.5, 5 and 10 mg/kg, p.o.) affects behavior in a chronic unpredictable stress model of depression in rats and examined what its molecular targets may be. We found that subjecting animals to the chronic stress protocol for 20days resulted in performance deficits in the shuttle-box task and several physiological effects, such as an abnormal adrenal gland weight to body weight (AG/B) ratio and increased thickness of the adrenal cortex as well as elevated serum corticosterone levels and reduced glucocorticoid receptor (GR) mRNA expression. These changes were reversed by chronic curcumin administration (5 or 10 mg/kg, p.o.). In addition, we also found that the chronic stress procedure induced a down-regulation of brain-derived neurotrophic factor (BDNF) protein levels and reduced the ratio of phosphorylated cAMP response element-binding protein (pCREB) to CREB levels (pCREB/CREB) in the hippocampus and frontal cortex of stressed rats. Furthermore, these stress-induced decreases in BDNF and pCREB/CREB were also blocked by chronic curcumin administration (5 or 10 mg/kg, p.o.). These results provide compelling evidence that the behavioral effects of curcumin in chronically stressed animals, and by extension humans, may be related to their modulating effects on the HPA axis and neurotrophin factor expressions.

Chronic and acute effects of stress on energy balance: are there appropriate animal models?

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Harris, Ruth B S

2015-02-15

Stress activates multiple neural and endocrine systems to allow an animal to respond to and survive in a threatening environment. The corticotropin-releasing factor system is a primary initiator of this integrated response, which includes activation of the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The energetic response to acute stress is determined by the nature and severity of the stressor, but a typical response to an acute stressor is inhibition of food intake, increased heat production, and increased activity with sustained changes in body weight, behavior, and HPA reactivity. The effect of chronic psychological stress is more variable. In humans, chronic stress may cause weight gain in restrained eaters who show increased HPA reactivity to acute stress. This phenotype is difficult to replicate in rodent models where chronic psychological stress is more likely to cause weight loss than weight gain. An exception may be hamsters subjected to repeated bouts of social defeat or foot shock, but the data are limited. Recent reports on the food intake and body composition of subordinate members of group-housed female monkeys indicate that these animals have a similar phenotype to human stress-induced eaters, but there are a limited number of investigators with access to the model. Few stress experiments focus on energy balance, but more information on the phenotype of both humans and animal models during and after exposure to acute or chronic stress may provide novel insight into mechanisms that normally control body weight. Copyright © 2015 the American Physiological Society.

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

Directory of Open Access Journals (Sweden)

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.

Dysregulated stress signal sensitivity and inflammatory disinhibition as a pathophysiological mechanism of stress-related chronic fatigue.

Science.gov (United States)

Strahler, Jana; Skoluda, Nadine; Rohleder, Nicolas; Nater, Urs M

2016-09-01

Chronic stress and its subsequent effects on biological stress systems have long been recognized as predisposing and perpetuating factors in chronic fatigue, although the exact mechanisms are far from being completely understood. In this review, we propose that sensitivity of immune cells to glucocorticoids (GCs) and catecholamines (CATs) may be the missing link in elucidating how stress turns into chronic fatigue. We searched for in vitro studies investigating the impact of GCs or CATs on mitogen-stimulated immune cells in chronically stressed or fatigued populations, with 34 original studies fulfilling our inclusion criteria. Besides mixed cross-sectional findings for stress- and fatigue-related changes of GC sensitivity under basal conditions or acute stress, longitudinal studies indicate a decrease with ongoing stress. Research on CATs is still scarce, but initial findings point towards a reduction of CAT sensitivity under chronic stress. In the long run, resistance of immune cells to stress signals under conditions of chronic stress might translate into self-maintaining inflammation and inflammatory disinhibition under acute stress, which in turn lead to fatigue. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

Jay, Kenneth; 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......: 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......, as outcome measures. RESULTS: A significant (P stress was observed (treatment by time P = 0.16). Exploratory analyses for each body...

Chronic stress affects immunologic but not cardiovascular responsiveness to acute psychological stress in humans

NARCIS (Netherlands)

Benschop, R. J.; Brosschot, J. F.; Godaert, G. L.; de Smet, M. B.; Geenen, R.; Olff, M.; Heijnen, C. J.; Ballieux, R. E.

1994-01-01

This study deals with the effect of chronic stress on physiological responsiveness to an acute psychological stressor in male high school teachers. Chronic stress was operationalized as the self-reported number of everyday problems. Twenty-seven subjects reporting extremely low or high numbers of

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 ...

Effect of chronic exposure to aspartame on oxidative stress in the ...

Indian Academy of Sciences (India)

2012-08-03

Aug 3, 2012 ... 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 ...

α2-adrenergic blockade mimics the enhancing effect of chronic stress on breast cancer progression

Science.gov (United States)

Lamkin, Donald M.; Sung, Ha Yeon; Yang, Gyu Sik; David, John M.; Ma, Jeffrey C.Y.; Cole, Steve W.; Sloan, Erica K.

2014-01-01

Experimental studies in preclinical mouse models of breast cancer have shown that chronic restraint stress can enhance disease progression by increasing catecholamine levels and subsequent signaling of β-adrenergic receptors. Catecholamines also signal α-adrenergic receptors, and greater α-adrenergic signaling has been shown to promote breast cancer in vitro and in vivo. However, antagonism of α-adrenergic receptors can result in elevated catecholamine levels, which may increase β-adrenergic signaling, because pre-synaptic α2-adrenergic receptors mediate an autoinhibition of sympathetic transmission. Given these findings, we examined the effect of α-adrenergic blockade on breast cancer progression under non-stress and stress conditions (chronic restraint) in an orthotopic mouse model with MDA-MB-231HM cells. Chronic restraint increased primary tumor growth and metastasis to distant tissues as expected, and non-selective α-adrenergic blockade by phentolamine significantly inhibited those effects. However, under non-stress conditions, phentolamine increased primary tumor size and distant metastasis. Sympatho-neural gene expression for catecholamine biosynthesis enzymes was elevated by phentolamine under non-stress conditions, and the non-selective β-blocker propranolol inhibited the effect of phentolamine on breast cancer progression. Selective α2-adrenergic blockade by efaroxan also increased primary tumor size and distant metastasis under non-stress conditions, but selective α1-adrenergic blockade by prazosin did not. These results are consistent with the hypothesis that α2-adrenergic signaling can act through an autoreceptor mechanism to inhibit sympathetic catecholamine release and, thus, modulate established effects of β-adrenergic signaling on tumor progression-relevant biology. PMID:25462899

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Directory of Open Access Journals (Sweden)

Beverley Greenwood-Van Meerveld

2017-11-01

Full Text Available Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS. Early life stress (ELS is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for

Stress-Induced Chronic Visceral Pain of Gastrointestinal Origin

Science.gov (United States)

Greenwood-Van Meerveld, Beverley; Johnson, Anthony C.

2017-01-01

Visceral pain is generally poorly localized and characterized by hypersensitivity to a stimulus such as organ distension. In concert with chronic visceral pain, there is a high comorbidity with stress-related psychiatric disorders including anxiety and depression. The mechanisms linking visceral pain with these overlapping comorbidities remain to be elucidated. Evidence suggests that long term stress facilitates pain perception and sensitizes pain pathways, leading to a feed-forward cycle promoting chronic visceral pain disorders such as irritable bowel syndrome (IBS). Early life stress (ELS) is a risk-factor for the development of IBS, however the mechanisms responsible for the persistent effects of ELS on visceral perception in adulthood remain incompletely understood. In rodent models, stress in adult animals induced by restraint and water avoidance has been employed to investigate the mechanisms of stress-induce pain. ELS models such as maternal separation, limited nesting, or odor-shock conditioning, which attempt to model early childhood experiences such as neglect, poverty, or an abusive caregiver, can produce chronic, sexually dimorphic increases in visceral sensitivity in adulthood. Chronic visceral pain is a classic example of gene × environment interaction which results from maladaptive changes in neuronal circuitry leading to neuroplasticity and aberrant neuronal activity-induced signaling. One potential mechanism underlying the persistent effects of stress on visceral sensitivity could be epigenetic modulation of gene expression. While there are relatively few studies examining epigenetically mediated mechanisms involved in visceral nociception, stress-induced visceral pain has been linked to alterations in DNA methylation and histone acetylation patterns within the brain, leading to increased expression of pro-nociceptive neurotransmitters. This review will discuss the potential neuronal pathways and mechanisms responsible for stress

Effect of Inhaling Bergamot Oil on Depression-Related Behaviors in Chronic Stressed Rats.

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Saiyudthong, Somrudee; Mekseepralard, Chantana

2015-10-01

Bergamot essential oil (BEO) possesses sedation and anxiolytic properties similar to diazepam. After long period of exposure to stressors, including restrained stress, depressive-like behavior can be produced. BEO has been suggested to reduce depression. However, there is no scientific evidence supporting this property. To investigate the effect of BEO in chronic stressed rats on: 1) behavior related depressive disorder, 2) hypothalamic pituitary adrenal (HPA) axis response, and iii) brain-derived neurotrophic factor (BDNF) protein levels in hippocampus. Male Wistar rats, weighing 200 to 250 g, were induced chronic restrained stress 15 minutes dailyfor two weeks. For the next two weeks, these rats were divided intofour groups, control-i.p., fluoxetine-i.p., control-inhale, and BEO-inhale. Fluoxetine (10 mg/kg i.p.) or saline was intraperitoneally administered daily while 2.5% BEO or saline was inhaled daily. At the end of the treatment, rats were assessed for depressive-like behavior using the forced swimming test (FST). After the behavioral test, the animals were immediately decapitated and trunk blood samples were collected for the measurement ofcorticosterone and adrenocorticotropic hormone (ACTH) levels and hippocampus was dissected and stored in afreezer at -80 °C until assay for BDNF protein. BEO andfluoxetine significantly decreased the immobility time in the FST (p BDNF protein determination, neither BEO norfluoxetine had any effect on BDNF protein levels in hippocampus compared to their controls. The inhalation ofBEO decrease behavior related depressive disorder similar tofluoxetine but has no effect on HPA axis response and BDNF protein levels in chronic restrained stress.

The Effect of Synchronized Forced Running with Chronic Stress on Short, Mid and Long- term Memory in Rats.

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

2013-03-01

Impairment of learning and memory processes has been demonstrated by many studies using different stressors. Other reports suggested that exercise has a powerful behavioral intervention to improve cognitive function and brain health. In this research, we investigated protective effects of treadmill running on chronic stress-induced memory deficit in rats. Fifty male Wistar rats were randomly divided into five groups (n=10) as follows: Control (Co), Sham (Sh), Stress (St), Exercise (Ex) and Stress and Exercise (St & Ex) groups. Chronic restraint stress was applied by 6h/day/21days and also treadmill running at a speed 20-21m/min for 1h/day/21days. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. OUR RESULTS SHOWED THAT: 1) Although exercise alone showed beneficial effects especially on short and mid-term memory (Pshort, mid and long-term memory deficit in stressed rats. 2) Short and mid-term memory deficit was significantly (PMemory deficit in synchronized exercise with stress group was nearly similar to stressed rats. 4) Helpful effects of exercise were less than harmful effects of stress when they were associated together. The data correspond to the possibility that although treadmill running alone has helpful effects on learning and memory consolidation, but when it is synchronized with stress there is no significant benefit and protective effects in improvement of memory deficit induced by chronic stress. However, it is has a better effect than no training on memory deficit in stressed rats.

Stress, intrusive imagery, and chronic distress

International Nuclear Information System (INIS)

Baum, A.

1990-01-01

Discusses the nature of stress in the context of problems with its definition and sources of confusion regarding its usefulness and specificity. Stress can be defined as a negative emotional experience accompanied by predictable biochemical, physiological, and behavioral changes that are directed toward adaptation either by manipulating the situation to alter the stressor or by accommodating its effects. Chronic stress is more complex than most definitions suggest and is clearly not limited to situations in which stressors persist for long periods of time. Responses may habituate before a stressor disappears or may persist long beyond the physical presence of the stressor. This latter case, in which chronic stress and associated biobehavioral changes outlast their original cause, is considered in light of research at Three Mile Island and among Vietnam veterans. The role of intrusive images of the stressor or uncontrollable thoughts about it in maintaining stress is explored

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

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Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

Chronic Pain and Chronic Stress: Two Sides of the Same Coin?

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Abdallah, Chadi G; Geha, Paul

2017-02-01

Pain and stress share significant conceptual and physiological overlaps. Both phenomena challenge the body's homeostasis and necessitate decision-making to help animals adapt to their environment. In addition, chronic stress and chronic pain share a common behavioral model of failure to extinguish negative memories. Yet, they also have discrepancies such that the final brain endophenotype of posttraumatic stress disorder, depression, and chronic pain appears to be different among the three conditions, and the role of the hypothalamic-pituitary-adrenal axis remains unclear in the physiology of pain. Persistence of either stress or pain is maladaptive and could lead to compromised well-being. In this brief review, we highlight the commonalities and differences between chronic stress and chronic pain, while focusing particularly on the central role of the limbic brain. We assess the current attempts in the field to conceptualize and understand chronic pain, within the context of knowledge gained from the stress literature. The limbic brain-including hippocampus, amygdala, and ventromedial pre-frontal cortex-plays a critical role in learning. These brain areas integrate incoming nociceptive or stress signals with internal state, and generate learning signals necessary for decision-making. Therefore, the physiological and structural remodeling of this learning circuitry is observed in conditions such as chronic pain, depression, and posttraumatic stress disorder, and is also linked to the risk of onset of these conditions.

Increasing adult hippocampal neurogenesis in mice after exposure to unpredictable chronic mild stress may counteract some of the effects of stress.

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Culig, Luka; Surget, Alexandre; Bourdey, Marlene; Khemissi, Wahid; Le Guisquet, Anne-Marie; Vogel, Elise; Sahay, Amar; Hen, René; Belzung, Catherine

2017-11-01

Major depression is hypothesized to be associated with dysregulations of the hypothalamic-pituitary-adrenal (HPA) axis and impairments in adult hippocampal neurogenesis. Adult-born hippocampal neurons are required for several effects of antidepressants and increasing the rate of adult hippocampal neurogenesis (AHN) before exposure to chronic corticosterone is sufficient to protect against its harmful effects on behavior. However, it is an open question if increasing AHN after the onset of chronic stress exposure would be able to rescue behavioral deficits and which mechanisms might be involved in recovery. We investigated this question by using a 10-week unpredictable chronic mild stress (UCMS) model on a transgenic mouse line (iBax mice), in which the pro-apoptotic gene Bax can be inducibly ablated in neural stem cells following Tamoxifen injection, therefore enhancing the survival of newborn neurons in the adult brain. We did not observe any effect of our treatment in non-stress conditions, but we did find that increasing AHN after 2 weeks of UCMS is sufficient to counteract the effects of UCMS on certain behaviors (splash test and changes in coat state) and endocrine levels and thus to display some antidepressant-like effects. We observed that increasing AHN lowered the elevated basal corticosterone levels in mice exposed to UCMS. This was accompanied by a tamoxifen-induced reversal of the lack of stress-induced decrease in neuronal activation in the anteromedial division of the bed nucleus of the stria terminalis (BSTMA) after intrahippocampal dexamethasone infusion, pointing to a possible mechanism through which adult-born neurons might have exerted their effects. Our results contribute to the neurogenesis hypothesis of depression by suggesting that increasing AHN may be beneficial not just before, but also after exposure to stress by counteracting several of its effects, in part through regulating the HPA axis. Copyright © 2017 Elsevier Ltd. All rights

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.

[Damage effects of chronic hypoxia on medulla oblongata associated with oxidative stress and cell apoptosis].

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Hou, Xuefei; Ding, Yan; Nie, Zheng; Li, Hui; Tang, Yuhong; Zhou, Hua; Chen, Li; Zheng, Yu

2012-08-01

The aim of this study is to study the damage effects of chronic hypoxia on medulla oblongata and to explore whether the damage is associated with oxidative stress and cell apoptosis. Adult male SD rats were randomly divided into two groups: control group and chronic hypoxia group. Medulla oblongata was obtained for the following methods of analyses. Nissl's staining was used to examine the Niss bodies of neurons in medullary respiratory related nuclei, biochemistry methods were utilized to examine oxidant stress damage induced by chronic hypoxia on medulla oblongata through measuring malondialdehyde (MDA) content and superoxide dismutase (SOD) activity, and RT-PCR technique was used to study the influence of apoptosis induced by chronic hypoxia on medulla oblongata through analyzing the levels of Bax mRNA and Bcl-2 mRNA. The results showed the optical densities of Nissl's staining in pre-BötC, NA, NTS, FN, and 12N were significantly decreased in chronic hypoxia group in comparison with that in control group (P 0.05). Bax mRNA expression had no obvious change and Bcl-2 mRNA expression significantly decreased in chronic hypoxia group in comparison with that in control group (P < 0.05). The results suggest that chronic hypoxia could bring about serious damage to medullary respiratory centers through aggravating oxidative stress and increasing cell apoptosis.

Effects of Stress and Relaxation on Central Pain Modulation in Chronic Whiplash and Fibromyalgia Patients Compared to Healthy Controls.

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Coppieters, Iris; Cagnie, Barbara; Nijs, Jo; van Oosterwijck, Jessica; Danneels, Lieven; De Pauw, Robby; Meeus, Mira

2016-03-01

Compelling evidence has demonstrated that impaired central pain modulation contributes to persistent pain in patients with chronic whiplash associated disorders (WAD) and fibromyalgia (FM). However, there is limited research concerning the influence of stress and relaxation on central pain modulation in patients with chronic WAD and FM. The present study aims to investigate the effects of acute cognitive stress and relaxation on central pain modulation in chronic WAD and FM patients compared to healthy individuals. A randomized crossover design was employed. The present study took place at the University of Brussels, the University Hospital Brussels, and the University of Antwerp. Fifty-nine participants (16 chronic WAD patients, 21 FM, 22 pain-free controls) were enrolled and subjected to various pain measurements. Temporal summation (TS) of pain and conditioned pain modulation (CPM) were evaluated. Subsequently, participants were randomly allocated to either a group that received progressive relaxation therapy or a group that performed a battery of cognitive tests (= cognitive stressor). Afterwards, all pain measurements were repeated. One week later participant groups were switched. A significant difference was found between the groups in the change in TS in response to relaxation (P = 0.008) and cognitive stress (P = 0.003). TS decreased in response to relaxation and cognitive stress in chronic WAD patients and controls. In contrast, TS increased after both interventions in FM patients. CPM efficacy decreased in all 3 groups in response to relaxation (P = 0.002) and cognitive stress (P = 0.001). The obtained results only apply for a single session of muscle relaxation therapy and cognitive stress, whereby no conclusions can be made for effects on pain perception and modulation of chronic cognitive stress and long-term relaxation therapies. A single relaxation session as well as cognitive stress may have negative acute effects on pain modulation in patients with

Chronic and Episodic Stress in Children of Depressed Mothers.

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

2016-01-01

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

Stress activates pronociceptive endogenous opioid signalling in DRG neurons during chronic colitis.

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Guerrero-Alba, Raquel; Valdez-Morales, Eduardo E; Jimenez-Vargas, Nestor N; Lopez-Lopez, Cintya; Jaramillo-Polanco, Josue; Okamoto, Takanobu; Nasser, Yasmin; Bunnett, Nigel W; Lomax, Alan E; Vanner, Stephen J

2017-12-01

Psychological stress accompanies chronic inflammatory diseases such as IBD, and stress hormones can exacerbate pain signalling. In contrast, the endogenous opioid system has an important analgesic action during chronic inflammation. This study examined the interaction of these pathways. Mouse nociceptive dorsal root ganglia (DRG) neurons were incubated with supernatants from segments of inflamed colon collected from patients with chronic UC and mice with dextran sodium sulfate (cDSS)-induced chronic colitis. Stress effects were studied by adding stress hormones (epinephrine and corticosterone) to dissociated neurons or by exposing cDSS mice to water avoidance stress. Changes in excitability of colonic DRG nociceptors were measured using patch clamp and Ca 2+ imaging techniques. Supernatants from patients with chronic UC and from colons of mice with chronic colitis caused a naloxone-sensitive inhibition of neuronal excitability and capsaicin-evoked Ca 2+ responses. Stress hormones decreased signalling induced by human and mouse supernatants. This effect resulted from stress hormones signalling directly to DRG neurons and indirectly through signalling to the immune system, leading to decreased opioid levels and increased acute inflammation. The net effect of stress was a change endogenous opioid signalling in DRG neurons from an inhibitory to an excitatory effect. This switch was associated with a change in G protein-coupled receptor excitatory signalling to a pathway sensitive to inhibitors of protein kinase A-protein, phospholipase C-protein and G protein βϒ subunits. Stress hormones block the inhibitory actions of endogenous opioids and can change the effect of opioid signalling in DRG neurons to excitation. Targeting these pathways may prevent heavy opioid use in IBD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

[Dynamics of hormone secretion during chronic emotional stress].

Science.gov (United States)

Amiragova, M G; Kovalev, S V; Svirskaia, R I

1979-05-01

Study of spontaneous secretion of corticosteroids and thyroid hormones and the direct hormonal response to stress revealed the pathogenic effect of chronic combined emotional stress upon the hormonal function of adrenal glands. The hippocampus takes part in formation of the emotional tension in response to stress stimulus and of the following hormonal secretion.

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.

Chronic stress-induced effects of corticosterone on brain: direct and indirect

NARCIS (Netherlands)

Dallman, M. F.; Akana, S. F.; Strack, A. M.; Scribner, K. S.; Pecoraro, N.; La Fleur, S. E.; Houshyar, H.; Gomez, F.

2004-01-01

Acutely, glucocorticoids act to inhibit stress-induced corticotrophin-releasing factor (CRF) and adrenocorticotrophic hormone (ACTH) secretion through their actions in brain and anterior pituitary (canonical feedback). With chronic stress, glucocorticoid feedback inhibition of ACTH secretion changes

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents.

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Eisenmann, Eric D; Rorabaugh, Boyd R; Zoladz, Phillip R

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

Science.gov (United States)

Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease (CVD) is the largest cause of mortality worldwide, and stress is a significant contributor to the development of CVD. The relationship between acute and chronic stress and CVD is well evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia–reperfusion injury (IRI). Conversely, chronic stress is arrhythmogenic and increases sensitivity to myocardial IRI. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions. PMID:27199778

Public Health Burden of Chronic Stress in a Transforming Society

Directory of Open Access Journals (Sweden)

Mária S. Kopp

2007-12-01

Full Text Available In this paper chronic stress is proposed as an integrating model that can be applied to the explanation of the suddenly changing patterns of premature mortality rates in transforming societies of Central-Eastern-Europe, especially in Hungary. The temporal factor in existing stress models is often neglected. Chronic stress has been shown to lead to typical pathogenetic results in animal experiments. Literature and the different models in the field of psychology, behavioural sciences, and epidemiology are reviewed in terms of the chronic stress theory. There are several conceptual bridges between psychological alterations and the risks, onset and prognosis of chronic disorders of great epidemiological significance. Depending on the field of research there are several parallel concepts which analyse practically the same phenomena. These are the stress theories in physiology, learned helplessness and control theory in psychology, depression research in psychiatry, the concept of vital exhaustion and the psychosocial risk research in sociology. Because chronic stress results in adverse health effects through biological, social and behavioural pathways, this theory might also havethe best explanatory power to understand the premature male morbidity and mortality crisis in Central and Eastern Europe in the last decades. The special features of premature mortality and morbidity crisis in Hungary might be regarded as an experimental model to understand better the human consequences of chronic stress and those processes where psychology meets physiology.

Effectiveness of neurofeedback therapy for anxiety and stress in adults living with a chronic illness: a systematic review protocol.

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Blaskovits, Farriss; Tyerman, Jane; Luctkar-Flude, Marian

2017-07-01

The objective of this review is to systematically examine the effectiveness of neurofeedback therapy for managing anxiety and stress in adults living with a chronic illness.The specific objectives are to identify which neurofeedback systems and/or protocols demonstrate effectiveness and determine the level of supporting evidence.The review question is as follows: What is the effectiveness of neurofeedback therapy for managing anxiety and stress in an adult population aged 18 years of age or older living with a chronic illness?

Chronic stress disrupts neural coherence between cortico-limbic structures

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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.

Role of anuloma viloma pranayama in reducing stress in chronic alcoholics

International Nuclear Information System (INIS)

Kumar, L.R.

2011-01-01

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

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

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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.

The effect of neuroscience education on pain, disability, anxiety, and stress in chronic musculoskeletal pain.

Science.gov (United States)

Louw, Adriaan; Diener, Ina; Butler, David S; Puentedura, Emilio J

2011-12-01

To evaluate the evidence for the effectiveness of neuroscience education (NE) for pain, disability, anxiety, and stress in chronic musculoskeletal (MSK) pain. Systematic searches were conducted on Biomed Central, BMJ.com, CINAHL, the Cochrane Library, NLM Central Gateway, OVID, ProQuest (Digital Dissertations), PsycInfo, PubMed/Medline, ScienceDirect, and Web of Science. Secondary searching (PEARLing) was undertaken, whereby reference lists of the selected articles were reviewed for additional references not identified in the primary search. All experimental studies including randomized controlled trials (RCTs), nonrandomized clinical trials, and case series evaluating the effect of NE on pain, disability, anxiety, and stress for chronic MSK pain were considered for inclusion. Additional limitations: studies published in English, published within the last 10 years, and patients older than 18 years. No limitations were set on specific outcome measures of pain, disability, anxiety, and stress. Data were extracted using the participants, interventions, comparison, and outcomes (PICO) approach. Methodological quality was assessed by 2 reviewers using the Critical Review Form-Quantitative Studies. This review includes 8 studies comprising 6 high-quality RCTs, 1 pseudo-RCT, and 1 comparative study involving 401 subjects. Most articles were of good quality, with no studies rated as poor or fair. Heterogeneity across the studies with respect to participants, interventions evaluated, and outcome measures used prevented meta-analyses. Narrative synthesis of results, based on effect size, established compelling evidence that NE may be effective in reducing pain ratings, increasing function, addressing catastrophization, and improving movement in chronic MSK pain. For chronic MSK pain disorders, there is compelling evidence that an educational strategy addressing neurophysiology and neurobiology of pain can have a positive effect on pain, disability, catastrophization, and

Acute stress decreases but chronic stress increases myocardial sensitivity to ischemic injury in rodents

Directory of Open Access Journals (Sweden)

Eric D Eisenmann

2016-04-01

Full Text Available Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and increases sensitivity to myocardial ischemia-reperfusion injury. Few studies have examined the impact of validated animal models of stress-related psychological disorders on the ischemic heart. This review examines the work that has been completed using rat models to study the effects of stress on myocardial sensitivity to ischemic injury. Utilization of animal models of stress-related psychological disorders is critical in the prevention and treatment of cardiovascular disorders in patients experiencing stress-related psychiatric conditions.

The effect of somatic awareness exercise on the chronic physical manifestations of the stress response

OpenAIRE

2013-01-01

M.Phil. (Biokinetics) Stress is an integral part of daily living and supports the ability to adapt. However, chronic activation without the ability to express the physical response results in overloading the physiological and psychological systems. Since urban South Africans are sedentary and experience high levels of stress, they are developing stress related chronic conditions and hypokinetic diseases (obesity, hypertension, depression). This study is aimed at decreasing the chronic phys...

Announced reward counteracts the effects of chronic social stress on anticipatory behavior and hippocampal synaptic plasticity in rats.

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Kamal, Amer; Van der Harst, Johanneke E; Kapteijn, Chantal M; Baars, Annemarie J M; Spruijt, Berry M; Ramakers, Geert M J

2010-04-01

Chronic stress causes insensitivity to rewards (anhedonia) in rats, reflected by the absence of anticipatory behavior for a sucrose-reward, which can be reversed by antidepressant treatment or repeated announced transfer to an enriched cage. It was, however, not clear whether the highly rewarding properties of the enriched cage alone caused this reversal or whether the anticipation of this reward as such had an additional effect. Therefore, the present study compared the consequences of the announcement of a reward to the mere effect of a reward alone with respect to their efficacy to counteract the consequences of chronic stress. Two forms of synaptic plasticity, long-term potentiation and long-term depression were investigated in area CA1 of the hippocampus. This was done in socially stressed rats (induced by defeat and subsequent long-term individual housing), socially stressed rats that received a reward (short-term enriched housing) and socially stressed rats to which this reward was announced by means of a stimulus that was repeatedly paired to the reward. The results were compared to corresponding control rats. We show that announcement of enriched housing appeared to have had an additional effect compared to the enriched housing per se as indicated by a significant higher amount of LTP. In conclusion, announced short-term enriched housing has a high and long-lasting counteracting efficacy on stress-induced alterations of hippocampal synaptic plasticity. This information is important for counteracting the consequences of chronic stress in both human and captive rats.

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

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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.

Chronic stress and illness in children: the role of allostatic load.

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Johnston-Brooks, C H; Lewis, M A; Evans, G W; Whalen, C K

1998-01-01

Recent studies of stress have highlighted the contributions of chronic psychological and environmental stressors to health and well-being. Children may be especially vulnerable to the negative effects of chronic stressors. Allostasis, the body's ability to adapt and adjust to environmental demands, has been proposed as an explanatory mechanism for the stress-health link, yet empirical evidence is minimal. This study tested the proposition that allostasis may be an underlying physiological mechanism linking chronic stress to poor health outcomes in school-aged children. Specifically, we examined whether allostasis would mediate or moderate the link between chronic stress and health. To test the hypothesis that allostasis contributes to the relation between chronic stress and poor health, we examined household density as a chronic environmental stressor, cardiovascular reactivity (CVR) as a marker of allostatic load, and number of school absences due to illness as the health outcome in a sample of 81 boys. Structural equation modeling indicated that the mediating model fit the data well, accounting for 17% of the variance in days ill. Results provide the first evidence that CVR may mediate the relation between household density and medical illness in children. More generally, these findings support the role of allostasis as an underlying mechanism in the link between chronic stress and health.

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

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

2012-12-01

The objective of this study was to evaluate the time-series relationships between stress, sleep duration, and headache pain among patients with chronic headaches. Sleep and stress have long been recognized as potential triggers of episodic headache (headache days/month), though prospective evidence is inconsistent and absent in patients diagnosed with chronic headaches (≥15 days/month). We reanalyzed data from a 28-day observational study of chronic migraine (n=33) and chronic tension-type headache (n=22) sufferers. Patients completed the Daily Stress Inventory and recorded headache and sleep variables using a daily sleep/headache diary. Stress ratings, duration of previous nights' sleep, and headache severity were modeled using a series of linear mixed models with random effects to account for individual differences in observed associations. Models were displayed using contour plots. Two consecutive days of either high stress or low sleep were strongly predictive of headache, whereas 2 days of low stress or adequate sleep were protective. When patterns of stress or sleep were divergent across days, headache risk was increased only when the earlier day was characterized by high stress or poor sleep. As predicted, headache activity in the combined model was highest when high stress and low sleep occurred concurrently during the prior 2 days, denoting an additive effect. Future research is needed to expand on current findings among chronic headache patients and to develop individualized models that account for multiple simultaneous influences of headache trigger factors. Copyright © 2012 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Agmatine attenuates chronic unpredictable mild stress induced behavioral alteration in mice.

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Taksande, Brijesh G; Faldu, Dharmesh S; Dixit, Madhura P; Sakaria, Jay N; Aglawe, Manish M; Umekar, Milind J; Kotagale, Nandkishor R

2013-11-15

Chronic stress exposure and resulting dysregulation of the hypothalamic pituitary adrenal axis develops susceptibility to variety of neurological and psychiatric disorders. Agmatine, a putative neurotransmitter has been reported to be released in response to various stressful stimuli to maintain the homeostasis. Present study investigated the role of agmatine on chronic unpredictable mild stress (CUMS) induced behavioral and biochemical alteration in mice. Exposure of mice to CUMS protocol for 28 days resulted in diminished performance in sucrose preference test, splash test, forced swim test and marked elevation in plasma corticosterone levels. Chronic agmatine (5 and 10 mg/kg, ip, once daily) treatment started on day-15 and continued till the end of the CUMS protocol significantly increased sucrose preference, improved self-care and motivational behavior in the splash test and decreased duration of immobility in the forced swim test. Agmatine treatment also normalized the elevated corticosterone levels and prevented the body weight changes in chronically stressed animals. The pharmacological effect of agmatine was comparable to selective serotonin reuptake inhibitor, fluoxetine (10mg/kg, ip). Results of present study clearly demonstrated the anti-depressant like effect of agmatine in chronic unpredictable mild stress induced depression in mice. Thus the development of drugs based on brain agmatinergic modulation may represent a new potential approach for the treatment of stress related mood disorders like depression. © 2013 Published by Elsevier B.V.

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.

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.

2012-01-01

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, 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. Following 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 food 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 precision 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 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 direct compared within the same animals following chronic stress, using FMI, an appetitive task, and RAWM, a non-appetitive task. PMID:22905921

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

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

2009-01-01

in the spontaneous alternation test, possibly reflecting a deficit in working memory. This effect was independent of whether the stressed rats were anhedonic-like or stress-resilient as measured by their sucrose intake. CMS did not influence performance in passive avoidance and auditory cued fear conditioning......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...

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.

History of chronic stress modifies acute stress-evoked fear memory and acoustic startle in male rats.

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Schmeltzer, Sarah N; Vollmer, Lauren L; Rush, Jennifer E; Weinert, Mychal; Dolgas, Charles M; Sah, Renu

2015-01-01

Chronicity of trauma exposure plays an important role in the pathophysiology of posttraumatic stress disorder (PTSD). Thus, exposure to multiple traumas on a chronic scale leads to worse outcomes than acute events. The rationale for the current study was to investigate the effects of a single adverse event versus the same event on a background of chronic stress. We hypothesized that a history of chronic stress would lead to worse behavioral outcomes than a single event alone. Male rats (n = 14/group) were exposed to either a single traumatic event in the form of electric foot shocks (acute shock, AS), or to footshocks on a background of chronic stress (chronic variable stress-shock, CVS-S). PTSD-relevant behaviors (fear memory and acoustic startle responses) were measured following 7 d recovery. In line with our hypothesis, CVS-S elicited significant increases in fear acquisition and conditioning versus the AS group. Unexpectedly, CVS-S elicited reduced startle reactivity to an acoustic stimulus in comparison with the AS group. Significant increase in FosB/ΔFosB-like immunostaining was observed in the dentate gyrus, basolateral amygdala and medial prefrontal cortex of CVS-S rats. Assessments of neuropeptide Y (NPY), a stress-regulatory transmitter associated with chronic PTSD, revealed selective reduction in the hippocampus of CVS-S rats. Collectively, our data show that cumulative stress potentiates delayed fear memory and impacts defensive responding. Altered neuronal activation in forebrain limbic regions and reduced NPY may contribute to these phenomena. Our preclinical studies support clinical findings reporting worse PTSD outcomes stemming from cumulative traumatization in contrast to acute trauma.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

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Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

Chronic and episodic stress predict physical symptom bother following breast cancer diagnosis.

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Harris, Lauren N; Bauer, Margaret R; Wiley, Joshua F; Hammen, Constance; Krull, Jennifer L; Crespi, Catherine M; Weihs, Karen L; Stanton, Annette L

2017-12-01

Breast cancer patients often experience adverse physical side effects of medical treatments. According to the biobehavioral model of cancer stress and disease, life stress during diagnosis and treatment may negatively influence the trajectory of women's physical health-related adjustment to breast cancer. This longitudinal study examined chronic and episodic stress as predictors of bothersome physical symptoms during the year after breast cancer diagnosis. Women diagnosed with breast cancer in the previous 4 months (N = 460) completed a life stress interview for contextual assessment of chronic and episodic stress severity at study entry and 9 months later. Physical symptom bother (e.g., pain, fatigue) was measured at study entry, every 6 weeks through 6 months, and at nine and 12 months. In multilevel structural equation modeling (MSEM) analyses, both chronic stress and episodic stress occurring shortly after diagnosis predicted greater physical symptom bother over the study period. Episodic stress reported to have occurred prior to diagnosis did not predict symptom bother in MSEM analyses, and the interaction between chronic and episodic stress on symptom bother was not significant. Results suggest that ongoing chronic stress and episodic stress occurring shortly after breast cancer diagnosis are important predictors of bothersome symptoms during and after cancer treatment. Screening for chronic stress and recent stressful life events in the months following diagnosis may help to identify breast cancer patients at risk for persistent and bothersome physical symptoms. Interventions to prevent or ameliorate treatment-related physical symptoms may confer added benefit by addressing ongoing non-cancer-related stress in women's lives.

Acute and chronic stress and the inflammatory response in hyperprolactinemic rats.

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Ochoa-Amaya, J E; Malucelli, B E; Cruz-Casallas, P E; Nasello, A G; Felicio, L F; Carvalho-Freitas, M I R

2010-01-01

Prolactin (PRL), a hormone produced by the pituitary gland, has multiple physiological functions, including immunoregulation. PRL can also be secreted in response to stressful stimuli. During stress, PRL has been suggested to oppose the immunosuppressive effects of inflammatory mediators. Therefore, the aim of the present study was to analyze the effects of short- and long-term hyperprolactinemia on the inflammatory response in rats subjected to acute or chronic cold stress. Inflammatory edema was induced by carrageenan in male rats, and hyperprolactinemia was induced by injections of the dopamine receptor antagonist domperidone. The volume of inflammatory edema was measured by plethysmography after carrageenan injection. Additionally, the effects of hyperprolactinemia on body weight and serum corticosterone levels were evaluated. Five days of domperidone-induced hyperprolactinemia increased the volume of inflammatory edema. No differences in serum corticosterone levels were observed between groups. No significant differences were found among 30 days domperidone-induced hyperprolactinemic animals subjected to acute stress and the inflammatory response observed in chronic hyperprolactinemic animals subjected to chronic stress. The results suggest that short-term hyperprolactinemia has pro-inflammatory effects. Because such an effect was not observed in long-term hyperprolactinemic animals, PRL-induced tolerance seems likely. We suggest that short-term hyperprolactinemia may act as a protective factor in rats subjected to acute stress. These data suggest that hyperprolactinemia and stress interact differentially according to the time period. Copyright 2010 S. Karger AG, Basel.

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

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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

2010-04-02

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. Copyright 2010 Elsevier B.V. All rights reserved.

Chronic stress from adolescence to aging in the prefrontal cortex: A neuroimmune perspective.

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Macht, Victoria A; Reagan, Lawrence P

2018-04-01

The development of the organism is a critical variable which influences the magnitude, duration, and reversibility of the effects of chronic stress. Such factors are relevant to the prefrontal cortex (PFC), as this brain region is the last to mature, the first to decline, and is highly stress-sensitive. Therefore, this review will examine the intersection between the nervous system and immune system at glutamatergic synapses in the PFC across three developmental periods: adolescence, adulthood, and aging. Glutamatergic synapses are tightly juxtaposed with microglia and astrocytes, and each of these cell types exhibits their own developmental trajectory. Not only does chronic stress differentially impact each of these cell types across development, but chronic stress also alters intercellular communication within this quad-partite synapse. These observations suggest that developmental shifts in both neural and immune function across neurons, microglia, and astrocytes mediate shifting effects of chronic stress on glutamatergic transmission. Copyright © 2018 Elsevier Inc. All rights reserved.

Chronic stress effects and their reversibility on the Fallopian tubes and uterus in rats.

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Divyashree, S; Yajurvedi, H N

2018-01-01

The durational effects of chronic stress on the Fallopian tubes and uterus were studied by exposing rats to stressors in the form of restraint (1h) and forced swimming (15min) daily for 4, 8 or 12 weeks. One group of stressed rats from each time period was then maintained without exposure to stressors for a further 4 weeks to assess their ability to recover from stress. All time periods of stress exposure resulted in decreased weight of the body and Fallopian tubes; however, the relative weight of the uterus and serum concentrations of oestradiol and insulin increased significantly. The antioxidant potential was decreased with increased malondialdehyde concentrations in the Fallopian tubes following all durations of exposure and after 4 and 8 weeks of stress exposure in the uterus. Interestingly, rats stressed for 12 weeks showed an increase in serum testosterone concentration and antioxidant enzyme activities with a decrease in malondialdehyde concentration in the uterus. The antioxidant enzyme activities and malondialdehyde concentration in the Fallopian tubes of all recovery group rats were similar to stressed rats. However, in the uterus these parameters were similar to controls in recovery group rats after 4 weeks or 8 weeks of exposure, but after 12 weeks of stress exposure these parameters did not return to control levels following the recovery period. These results reveal, for the first time, that chronic stress elicits an irreversible decrease in antioxidant defence in the Fallopian tubes irrespective of exposure duration, whereas the uterus develops reversible oxidative stress under short-term exposure but increased antioxidant potential with endometrial proliferation following long-term exposure.

Inactivation of basolateral amygdala prevents chronic immobilization stress-induced memory impairment and associated changes in corticosterone levels.

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Tripathi, Sunil Jamuna; Chakraborty, Suwarna; Srikumar, B N; Raju, T R; Shankaranarayana Rao, B S

2017-07-01

Chronic stress causes detrimental effects on various forms of learning and memory. The basolateral amygdala (BLA) not only plays a crucial role in mediating certain forms of memory, but also in the modulation of the effects of stress. Chronic immobilization stress (CIS) results in hypertrophy of the BLA, which is believed to be one of the underlying causes for stress' effects on learning. Thus, it is plausible that preventing the effects of CIS on amygdala would preclude its deleterious cognitive effects. Accordingly, in the first part, we evaluated the effect of excitotoxic lesion of the BLA on chronic stress-induced hippocampal-dependent spatial learning using a partially baited radial arm maze task. The BLA was ablated bilaterally using ibotenic acid prior to CIS. Chronically stressed rats showed impairment in spatial learning with decreased percentage correct choice and increased reference memory errors. Excitotoxic lesion of the BLA prevented the impairment in spatial learning and reference memory. In the retention test, lesion of the BLA was able to rescue the chronic stress-induced impairment. Interestingly, stress-induced enhanced plasma corticosterone levels were partially prevented by the lesion of BLA. These results motivated us to evaluate if the same effects can be observed with temporary inactivation of BLA, only during stress. We found that chronic stress-induced spatial learning deficits were also prevented by temporary inactivation of the BLA. Additionally, temporary inactivation of BLA partially precluded the stress-induced increase in plasma corticosterone levels. Thus, inactivation of BLA precludes stress-induced spatial learning deficits, and enhanced plasma corticosterone levels. It is speculated that BLA inactivation-induced reduction in corticosterone levels during stress, might be crucial in restoring spatial learning impairments. Our study provides evidence that amygdalar modulation during stress might be beneficial for strategic

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

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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.

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

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

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...

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

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Li-Li Wu

2016-01-01

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

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

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Tryon, M S; DeCant, Rashel; Laugero, K D

2013-04-10

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 visceral fat and inhibits acute stress-induced hypothalamic-pituitary-adrenal (HPA) axis activity. The effect of chronic stress on eating behavior in humans is less understood, but it may be linked to HPA responsivity. The purpose of this study was to investigate the influence of chronic social stress and acute stress reactivity on food choice and food intake. Forty-one women (BMI=25.9±5.1 kg/m(2), age range=41 to 52 years) were subjected to the Trier Social Stress Test or a control task (nature movie) to examine HPA responses to an acute laboratory stressor and then invited to eat from a buffet containing low- and high-calorie snacks. Women were also categorized as high chronic stress or low chronic stress based on Wheaton Chronic Stress Inventory scores. Women reporting higher chronic stress and exhibiting low cortisol reactivity to the acute stress task consumed significantly more calories from chocolate cake on both stress and control visits. Chronic stress in the low cortisol reactor group was also positively related to total fat mass, body fat percentage, and stress-induced negative mood. Further, women reporting high chronic stress consumed significantly less vegetables, but only in those aged 45 years and older. Chronic stress in women within the higher age category was positively related to total calories consumed at the buffet, stress-induced negative mood and food craving. Our results suggest an increased risk for stress eating in persons with a specific chronic stress signature and imply that a habit of comfort food may link chronic social stress and acute stress-induced cortisol hyporesponsiveness. Published by Elsevier Inc.

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

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Susana eMonteiro

2015-02-01

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

Emotionality Modulates the Effect of Chronic Stress on Feeding Behaviour in Birds

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Favreau-Peigné, Angélique; Calandreau, Ludovic; Constantin, Paul; Gaultier, Bernard; Bertin, Aline; Arnould, Cécile; Laurence, Agathe; Richard-Yris, Marie-Annick; Houdelier, Cécilia; Lumineau, Sophie; Boissy, Alain; Leterrier, Christine

2014-01-01

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 depending on their

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

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

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

2015-10-01

Evaluate whether levels of upsetting life events measured over a 9-y period prospectively predict subjective and objective sleep outcomes in midlife women. Prospective cohort study. Four sites across the United States. 330 women (46-57 y of age) enrolled in the Study of Women's Health Across the Nation (SWAN) Sleep Study. N/A. Upsetting life events were assessed annually for up to 9 y. Trajectory analysis applied to life events data quantitatively identified three distinct chronic stress groups: low stress, moderate stress, and high stress. Sleep was assessed by self-report and in-home polysomnography (PSG) during the ninth year of the study. Multivariate analyses tested the prospective association between chronic stress group and sleep, adjusting for race, baseline sleep complaints, marital status, body mass index, symptoms of depression, and acute life events at the time of the Sleep Study. Women characterized by high chronic stress had lower subjective sleep quality, were more likely to report insomnia, and exhibited increased PSG-assessed wake after sleep onset (WASO) relative to women with low to moderate chronic stress profiles. The effect of chronic stress group on WASO persisted in the subsample of participants without baseline sleep complaints. Chronic stress is prospectively associated with sleep disturbance in midlife women, even after adjusting for acute stressors at the time of the sleep study and other factors known to disrupt sleep. These results are consistent with current models of stress that emphasize the cumulative effect of stressors on health over time. © 2015 Associated Professional Sleep Societies, LLC.

Anhedonia but not passive floating is an indicator of depressive-like behavior in two chronic stress paradigms.

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Stepanichev, Mikhail Yu; Tishkina, Anna O; Novikova, Margarita R; Levshina, Irina P; Freiman, Sofiya V; Onufriev, Mikhail V; Levchenko, Olga A; Lazareva, Natalia A; Gulyaeva, Natalia V

2016-01-01

Depression is the most common form of mental disability in the world. Depressive episodes may be precipitated by severe acute stressful events or by mild chronic stressors. Studies on the mechanisms of depression require both appropriate experimental models (most of them based on the exposure of animals to chronic stressors), and appropriate tests for assessment of depressive states. In this study male Wistar rats were exposed to two different chronic stress paradigms: an eight-week chronic unpredictable mild stress or a two-week combined chronic stress. The behavioral effects of stress were evaluated using sucrose preference, forced swim and open field tests. After the exposure to chronic unpredictable mild stress, anhedonia was developed, activity in the open field increased, while no changes in the duration of passive floating could be detected. After chronic combined stress, anhedonia was also evident, whereas behavior in the open field and forced swim test did not change. The levels of corticosterone in the blood and brain structures involved in stress-response did not differ from control in both experiments. The absence of significant changes in corticosterone levels and passive floating may be indicative of the adaptation of animals to chronic stress. Anhedonia appears to be a more sensitive indicator of depressive-like behavioral effects of chronic stress as compared to behavior in the forced swim or open field tests.

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.

Effects of chronic multiple stress on learning and memory and the expression of Fyn, BDNF, TrkB in the hippocampus of rats.

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Li, Xiao-Heng; Liu, Neng-Bao; Zhang, Min-Hai; Zhou, Yan-Ling; Liao, Jia-Wan; Liu, Xiang-Qian; Chen, Hong-Wei

2007-04-20

The effect of chronic stress on cognitive functions has been one of the hot topics in neuroscience. But there has been much controversy over its mechanism. The aim of this study was to investigate the effects of chronic multiple stress on spatial learning and memory as well as the expression of Fyn, BDNF and TrkB in the hippocampus of rats. Adult rats were randomly divided into control and chronic multiple stressed groups. Rats in the multiple stressed group were irregularly and alternatively exposed to situations of vertical revolution, sleep expropriation and restraint lasting for 6 weeks, 6 hours per day with night illumination for 6 weeks. Before and after the period of chronic multiple stresses, the performance of spatial learning and memory of all rats was measured using the Morris Water Maze (MWM). The expression of Fyn, BDNF and TrkB proteins in the hippocampus was assayed by Western blotting and immunohistochemical methods. The levels of Fyn and TrkB mRNAs in the hippocampus of rats were detected by RT-PCR technique. The escape latency in the control group and the stressed group were 15.63 and 8.27 seconds respectively. The performance of spatial learning and memory of rats was increased in chronic multiple stressed group (P < 0.05). The levels of Fyn, BDNF and TrkB proteins in the stressed group were higher than those of the control group (P < 0.05). The results of immunoreactivity showed that Fyn was present in the CA3 region of the hippocampus and BDNF positive particles were distributed in the nuclei of CA1 and CA3 pyramidal cells as well as DG granular cells. Quantitative analysis indicated that level of Fyn mRNA was also upregulated in the hippocampus of the stressed group (P < 0.05). Chronic multiple stress can enhance spatial learning and memory function of rats. The expression of Fyn, BDNF and TrkB proteins and the level of Fyn mRNA are increased in the stessed rat hippocampus. These suggest that Fyn and BDNF/TrkB signal transduction pathways may

Chronic stress does not impair liver regeneration in rats

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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...

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

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

2016-01-01

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

Effects of acute and chronic administration of methylprednisolone on oxidative stress in rat lungs

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Ronaldo Lopes Torres

2014-06-01

Full Text Available Objective: To determine the effects of acute and chronic administration of methylprednisolone on oxidative stress, as quantified by measuring lipid peroxidation (LPO and total reactive antioxidant potential (TRAP, in rat lungs. Methods: Forty Wistar rats were divided into four groups: acute treatment, comprising rats receiving a single injection of methylprednisolone (50 mg/kg i.p.; acute control, comprising rats i.p. injected with saline; chronic treatment, comprising rats receiving methylprednisolone in drinking water (6 mg/kg per day for 30 days; and chronic control, comprising rats receiving normal drinking water. Results: The levels of TRAP were significantly higher in the acute treatment group rats than in the acute control rats, suggesting an improvement in the pulmonary defenses of the former. The levels of lung LPO were significantly higher in the chronic treatment group rats than in the chronic control rats, indicating oxidative damage in the lung tissue of the former. Conclusions: Our results suggest that the acute use of corticosteroids is beneficial to lung tissue, whereas their chronic use is not. The chronic use of methylprednisolone appears to increase lung LPO levels.

Comparative antistress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats

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Manish Pal Singh

2016-07-01

Full Text Available Introduction: The human society has become complex. However, our physiological responses designed to cope with the ever-increasing adverse situations have not evolved appreciably during the past thousand years. The failure of successful adaptation during stressful situations has resulted in stress-related illnesses. Methods: The objective of the present study was to carry out a comparative assessment of anti-stress effect of Vitis vinifera and Withania somnifera using unpredictable chronic mild stress model in rats. Long-term exposure to multiple stressors can cause depression. The unpredictable chronic administration of various mild stresses, a procedure known as “unpredictable chronic mild stress”, is one of the best-validated rodent models to study stress in animals, for its good etiological and predictive validity. Result: Diazepam, Withania somnifera, Vitis vinifera administration dose dependently reversed the increase in immobility period in stressed rats. In the study of locomotion activity of rats in elevated plus maze apparatus, Stress treated control group rats showed less no of entries in open arm and also less time spent in open arm. Vitis vinifera treated (p<0.0001, Withania somnifera treated (p<0.0001 and Diazepam treated group showed (p<0.0001 no. of entries in open arms which were more than control group and stressed groups. Stressed group produce less average time spent in open arm as compared to treatment groups as Withania somnifera (p<0.05, Vitis vinifera and diazepam. Withania somnifera group showed significant antistress locomotry behaviour in rats. Administration of Vitis vinifera, Withania somnifera and diazepam during stress period restored the ambulatory behaviour of the rats which can be correlated with restoration of plasma corticosterone level. Finally, the results of the present study justified that Withania somnifera, Vitis vinifera and diazepam exhibited significant antistress activity in rats.

Quercetin prevents chronic unpredictable stress induced behavioral dysfunction in mice by alleviating hippocampal oxidative and inflammatory stress.

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Mehta, Vineet; Parashar, Arun; Udayabanu, Malairaman

2017-03-15

It is now evident that chronic stress is associated with anxiety, depression and cognitive dysfunction and very few studies have focused on identifying possible methods to prevent these stress-induced disorders. Previously, we identified abundance of quercetin in Urtica dioica extract, which efficiently attenuated stress related complications. Therefore, current study was designed to investigate the effect of quercetin on chronic unpredicted stress (CUS) induced behavioral dysfunction, oxidative stress and neuroinflammation in the mouse hippocampus. Animals were subjected to unpredicted stress for 21days, during which 30mg/kg quercetin was orally administered to them. Effect of CUS and quercetin treatment on animal behavior was assessed between day 22-26. Afterward, the hippocampus was processed to evaluate neuronal damage, oxidative and inflammatory stress. Results revealed that stressed animals were highly anxious (Elevated Plus Maze and Open Field), showed depressive-like behavior (sucrose preference task), performed poorly in short-term and long-term associative memory task (passive avoidance step-through task) and displayed reduced locomotion (open field). Quercetin alleviated behavioral dysfunction in chronically stressed animals. Compared to CUS, quercetin treatment significantly reduced anxiety, attenuated depression, improved cognitive dysfunction and normalized locomotor activity. Further, CUS elevated the levels of oxidative stress markers (TBARS, nitric oxide), lowered antioxidants (total thiol, catalase), enhanced expression of pro-inflammatory cytokines (IL-6, TNF-α, IL-1β and COX-2) in the hippocampus and damaged hippocampal neurons. Quercetin treatment significantly lowered oxidative and inflammatory stress and prevented neural damage. In conclusion, quercetin can efficiently prevent stress induced neurological complications by rescuing brain from oxidative and inflammatory stress. Copyright © 2017 Elsevier Inc. All rights reserved.

Parental alcohol use disorders and child delinquency: the mediating effects of executive functioning and chronic family stress.

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Grekin, Emily R; Brennan, Patricia A; Hammen, Constance

2005-01-01

This study examines the relationship between parental alcohol use disorders (AUDs) and child violent and nonviolent delinquency. It also explores the mediating effects of executive functioning and chronic family stress on the parental AUD/child delinquency relationship. Participants were 816 families with children (414 boys and 402 girls) born between 1981 and 1984 at Mater Misericordiae Mother's Hospital in Brisbane, Australia. Parents and children completed semistructured interviews, questionnaires and neuropsychological tests that assessed parental alcohol use, family psychiatric history, chronic family stress, child delinquency and child executive functioning. Paternal (but not maternal) AUDs predicted child violent and nonviolent delinquency. Executive functioning mediated the relationship between paternal AUDs and violent delinquency, whereas family stress mediated the relationship between paternal AUDs and both violent and nonviolent delinquency. Results support a biosocial conceptualization of the paternal AUD/delinquency relationship. They suggest that paternal AUDs may be associated with child executive functioning and family stress, which may in turn lead to child delinquency.

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

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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. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

[Effects of chronic experimental stress and endogenous opioids on histophysiological parameters of the thyroid gland].

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Krasnoperov, R A; Glumova, V A; Riashchikov, S N; Proshutina, N E

1992-01-01

In adult rabbits stress was modelled by electrostimulation of the hypothalamus ventromedial nucleus (15-hour-long session during 30 days) and medulla's raphe big nucleus which is one of the central places of the opioid peptides synthesis was irritated. It is revealed, that under stress thyroid gland responds by serum T3 increase in comparison with control animals with statistically significant variability of the T4 profile. Chronicity of the emotional agitation involves destructive changes in the thyroid parenchyma the hurting effect of the negative emotional factor is expressed less during opioid peptides complex activation. It is suggested that there are its own stress-limiting mechanisms in thyroid gland.

Age-related effects of chronic restraint stress on ethanol drinking, ethanol-induced sedation, and on basal and stress-induced anxiety response.

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Fernández, Macarena Soledad; Fabio, María Carolina; Miranda-Morales, Roberto Sebastián; Virgolini, Miriam B; De Giovanni, Laura N; Hansen, Cristian; Wille-Bille, Aranza; Nizhnikov, Michael E; Spear, Linda P; Pautassi, Ricardo Marcos

2016-03-01

Adolescents are sensitive to the anxiolytic effect of ethanol, and evidence suggests that they may be more sensitive to stress than adults. Relatively little is known, however, about age-related differences in stress modulation of ethanol drinking or stress modulation of ethanol-induced sedation and hypnosis. We observed that chronic restraint stress transiently exacerbated free-choice ethanol drinking in adolescent, but not in adult, rats. Restraint stress altered exploration patterns of a light-dark box apparatus in adolescents and adults. Stressed animals spent significantly more time in the white area of the maze and made significantly more transfers between compartments than their non-stressed peers. Behavioral response to acute stress, on the other hand, was modulated by prior restraint stress only in adults. Adolescents, unlike adults, exhibited ethanol-induced motor stimulation in an open field. Stress increased the duration of loss of the righting reflex after a high ethanol dose, yet this effect was similar at both ages. Ethanol-induced sleep time was much higher in adult than in adolescent rats, yet stress diminished ethanol-induced sleep time only in adults. The study indicates age-related differences that may increase the risk for initiation and escalation in alcohol drinking. Copyright © 2016 Elsevier Inc. All rights reserved.

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

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

2015-01-01

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

Balancing food and predator pressure induces chronic stress in songbirds.

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

2004-01-01

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

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

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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)

Acute Stress Decreases but Chronic Stress Increases Myocardial Sensitivity to Ischemic Injury in Rodents

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Eisenmann, Eric D.; Rorabaugh, Boyd R.; Zoladz, Phillip R.

2016-01-01

Cardiovascular disease is the largest cause of mortality worldwide, and stress is a significant contributor to the development of cardiovascular disease. The relationship between acute and chronic stress and cardiovascular disease is well-evidenced. Acute stress can lead to arrhythmias and ischemic injury. However, recent evidence in rodent models suggests that acute stress can decrease sensitivity to myocardial ischemia-reperfusion injury. Conversely, chronic stress is arrythmogenic and incr...

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.

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

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Meng, Zhen-Zhi; Chen, Jia-Xu; Jiang, You-Ming; Zhang, Han-Ting

2013-01-01

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 w...

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.

Dysfunctional stress responses in chronic pain.

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Woda, Alain; Picard, Pascale; Dutheil, Frédéric

2016-09-01

Many dysfunctional and chronic pain conditions overlap. This review describes the different modes of chronic deregulation of the adaptive response to stress which may be a common factor for these conditions. Several types of dysfunction can be identified within the hypothalamo-pituitary-adrenal axis: basal hypercortisolism, hyper-reactivity, basal hypocortisolism and hypo-reactivity. Neuroactive steroid synthesis is another component of the adaptive response to stress. Dehydroepiandrosterone (DHEA) and its sulfated form DHEA-S, and progesterone and its derivatives are synthetized in cutaneous, nervous, and adipose cells. They are neuroactive factors that act locally. They may have a role in the localization of the symptoms and their levels can vary both in the central nervous system and in the periphery. Persistent changes in neuroactive steroid levels or precursors can induce localized neurodegeneration. The autonomic nervous system is another component of the stress response. Its dysfunction in chronic stress responses can be expressed by decreased basal parasympathethic activity, increased basal sympathetic activity or sympathetic hyporeactivity to a stressful stimulus. The immune and genetic systems also participate. The helper-T cells Th1 secrete pro-inflammatory cytokines such as IL-1-β, IL-2, IL-6, IL-8, IL-12, IFN-γ, and TNF-α, whereas Th2 secrete anti-inflammatory cytokines: IL-4, IL-10, IGF-10, IL-13. Chronic deregulation of the Th1/Th2 balance can occur in favor of anti- or pro-inflammatory direction, locally or systemically. Individual vulnerability to stress can be due to environmental factors but can also be genetically influenced. Genetic polymorphisms and epigenetics are the main keys to understanding the influence of genetics on the response of individuals to constraints. Copyright © 2016 Elsevier Ltd. All rights reserved.

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.

A Presence-Based Context-Aware Chronic Stress Recognition System

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Andrej Kos

2012-11-01

Full Text Available Stressors encountered in daily life may play an important role in personal well-being. Chronic stress can have a serious long-term impact on our physical as well as our psychological health, due to ongoing increased levels of the chemicals released in the ‘fight or flight’ response. The currently available stress assessment methods are usually not suitable for daily chronic stress measurement. The paper presents a context-aware chronic stress recognition system that addresses this problem. The proposed system obtains contextual data from various mobile sensors and other external sources in order to calculate the impact of ongoing stress. By identifying and visualizing ongoing stress situations of an individual user, he/she is able to modify his/her behavior in order to successfully avoid them. Clinical evaluation of the proposed methodology has been made in parallel by using electrodermal activity sensor. To the best of our knowledge, the system presented herein is the first one that enables recognition of chronic stress situations on the basis of user context.

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. Copyright © 2013 Elsevier B.V. All rights reserved.

Influence of chronic stress and oclusal interference on masseter muscle pain in rat.

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Simonić-Kocijan, Suncana; Uhac, Ivone; Braut, Vedrana; Kovac, Zoran; Pavicić, Daniela Kovacević; Fugosić, Vesna; Urek, Miranda Muhvić

2009-09-01

This study aimed to investigate the individual effects of chronic stress and occlusal interference, as well as their combined influence on masseter muscle pain. Experiments were performed on 28 male Wistar rats. Animals were submitted to chronic stress procedure, exposed to occlusal interference, or exposed to both mantioned procedures. At the end of the procedure animals were submitted to orofacial formalin test, and nociceptive behavioral response was evaluated. Statisticaly significant difference of nociceptive behavioral response in chronicaly stressed rats and in the animals with occlusal interference in comparation to the control group were not obtained (p > 0.05). In contrast, nociceptive behavioral response was significantly increased in rats submitted to both of experimental procedures (p occlusal interference and chronic stress influence masseter muscle pain.

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

Directory of Open Access Journals (Sweden)

Peter Vestergaard-Poulsen

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

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

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

2016-05-01

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

Curcumin, a polyphenolic antioxidant, attenuates chronic fatigue syndrome in murine water immersion stress model.

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Gupta, Amit; Vij, Garima; Sharma, Sameer; Tirkey, Naveen; Rishi, Praveen; Chopra, Kanwaljit

2009-01-01

Chronic fatigue syndrome, infection and oxidative stress are interrelated in epidemiological case studies. However, data demonstrating scientific validation of epidemiological claims regarding effectiveness of nutritional supplements for chronic fatigue syndrome are lacking. This study is designed to evaluate the effect of natural polyphenol, curcumin, in a mouse model of immunologically induced fatigue, where purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigens were used as immunogens. The assessment of chronic fatigue syndrome was based on chronic water-immersion stress test for 10 min daily for 19 days and the immobility time was taken as the marker of fatigue. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time and hyperalgesia on day 19, as well as marked increase in serum tumor necrosis factor-alpha (TNF-alpha) levels. Concurrent treatment with curcumin resulted in significantly decreased immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as TNF-alpha levels. These findings strongly suggest that during immunological activation, there is significant increase in oxidative stress and curcumin can be a valuable option in the treatment of chronic fatigue syndrome.

Protective effects of Andrographis paniculata extract and pure andrographolide against chronic stress-triggered pathologies in rats.

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Thakur, Ajit Kumar; Soni, Upendra Kumar; Rai, Geeta; Chatterjee, Shyam Sunder; Kumar, Vikas

2014-11-01

This study was designed to experimentally verify the possibility that Andrographis paniculata could be another medicinal herb potentially useful for prevention of diverse spectrums of pathologies commonly associated with chronic unavoidable environmental stress, and whether andrographolide could as well be its quantitatively major bioactive secondary metabolite. Preventive effects of 21 daily oral 50, 100 and 200 mg/kg doses of a therapeutically used extract of the plant (AP) and 30 and 60 mg/kg/day of pure andrographolide were compared in rats subjected to 1-h daily unavoidable foot-shocks. A pharmaceutically well-standardized Withania somnifera (WS) root extract was used as a reference herbal anti-stress agent in all experiments. Effects of the treatments on stress-induced alterations in body weight, gastric ulcer, adrenal and spleen weights, and depressive state and sexual behavior in male rats were quantified. Other parameters quantified were plasma cortisol levels, and expressions of the cytokines TNF-α, IL-10 and IL-1β in blood and brain. All observed stress-induced pathological changes were less pronounced or completely prevented by both AP and pure andrographolide. Even the lowest tested doses of AP (50 mg/kg/day) or of andrographolide (30 mg/kg/day) suppressed almost maximally the blood IL-1β and IL-10 as well as brain TNF-α and IL-10 expressions induced by chronic stress. Qualitatively, the observed activity profiles of both of them were similar to those of WS dose tested. These results reveal that both AP and andrographolide are pharmacologically polyvalent anti-stress agents, and that biological processes regulating corticosterone and cytokine homeostasis are involved in their modes of actions.

Effects of berberine on a rat model of chronic stress and depression via gastrointestinal tract pathology and gastrointestinal flora profile assays.

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Zhu, Xiaohui; Sun, Yangdong; Zhang, Chenggang; Liu, Haifeng

2017-05-01

Chronic stress and depression are challenging conditions to treat, owing to their complexity and lack of clinically available and effective therapeutic agents. The aim of the present study was to investigate the mechanism by which berberine acts, by examining alterations to gastrointestinal tract histopathology and flora profile in a rat model, following the induction of stress. Research associating gastrointestinal flora and depression has increased, thus, the present study hypothesized that stress induces depression and changes in the gastrointestinal system. The chronic mild stress rat model was previously established based on a set of 10 chronic unpredictable stress methods. In the present study, the measurements of body weight, behavior, gastrointestinal tract histopathology and gastrointestinal flora profile were collected in order to elucidate understanding of chronic stress and depression in this region. In the present study, induced stress and the resulting depression was demonstrated to significantly decrease the body weight and sucrose preference of rats, as well as significantly increasing traverse time, vertical movement time, grooming time and motionless time in an open‑field test. Following modeling and subsequent treatment with low or high doses of berberine, the measurements were significantly different when compared with unstressed rats. Berberine appears to reverse the physical damage brought about by stress within the gastric mucosa and intestinal microvilli of the stomach, ileum, cecum and colon. Using enterobacterial repetitive intergenic consensus sequence‑based polymerase chain reaction analysis, several distinctive bands disappeared following modeling; however, novel distinctive bands appeared in response to the graded berberine treatment. In conclusion, the present study identified that high concentrations of berberine markedly protects rats from various symptoms of chronic stress and depression, with the potential of facilitating

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

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

2015-01-01

A number of studies have recently focused on the neuroprotective and anti-inflammatory effects of resveratrol. In prior studies, we described its beneficial effects on scopolamine-induced learning deficits in rats. The aim of this study was to investigate the effects of resveratrol on emotional and spatial cognitive functions, neurotropic factor expression, and plasma levels of proinflammatory cytokines in rats exposed to chronic unpredictable mild stress (CUMS), which is known to induce cognitive deficits. Resveratrol (5 or 20mg/kg) was administered intraperitoneally for 35 days. Rats in the CUMS group and in the 5mg/kg resveratrol+CUMS group performed poorly in tasks designed to assess emotional and spatial learning and memory. The 20mg/kg resveratrol+CUMS group showed improved performance compared to the CUMS group. In addition, the CUMS procedure induced lower expression of brain-derived neurotrophic factor and c-Fos in hippocampal CA1 and CA3 and in the amygdala of stressed rats. These effects were reversed by chronic administration of resveratrol (20mg/kg). In addition, plasma levels of tumor necrosis factor-alpha and interleukin-1 beta were increased by CUMS, but were restored to normal by resveratrol. These results indicate that resveratrol significantly attenuates the deficits in emotional learning and spatial memory seen in chronically stressed rats. These effects may be related to resveratrol-mediated changes in neurotrophin factor expression in hippocampus and in levels of proinflammatory cytokines in circulation. Copyright © 2014 Elsevier Inc. All rights reserved.

Too much of a good thing: blocking noradrenergic facilitation in medial prefrontal cortex prevents the detrimental effects of chronic stress on cognition.

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Jett, Julianne D; Morilak, David A

2013-03-01

Cognitive impairments associated with dysfunction of the medial prefrontal cortex (mPFC) are prominent in stress-related psychiatric disorders. We have shown that enhancing noradrenergic tone acutely in the rat mPFC facilitated extra-dimensional (ED) set-shifting on the attentional set-shifting test (AST), whereas chronic unpredictable stress (CUS) impaired ED. In this study, we tested the hypothesis that the acute facilitatory effect of norepinephrine (NE) in mPFC becomes detrimental when activated repeatedly during CUS. Using microdialysis, we showed that the release of NE evoked in mPFC by acute stress was unchanged at the end of CUS treatment. Thus, to then determine if repeated elicitation of this NE activity in mPFC during CUS may have contributed to the ED deficit, we infused a cocktail of α(1)-, β(1)-, and β(2)-adrenergic receptor antagonists into the mPFC prior to each CUS session, then tested animals drug free on the AST. Antagonist treatment prevented the CUS-induced ED deficit, suggesting that NE signaling during CUS compromised mPFC function. We confirmed that this was not attributable to sensitization of adrenergic receptor function following chronic antagonist treatment, by administering an additional microinjection into the mPFC immediately prior to ED testing. Acute antagonist treatment did not reverse the beneficial effects of chronic drug treatment during CUS, nor have any effect on baseline ED performance in chronic vehicle controls. Thus, we conclude that blockade of noradrenergic receptors in mPFC protected against the detrimental cognitive effects of CUS, and that repeated elicitation of noradrenergic facilitatory activity is one mechanism by which chronic stress may promote mPFC cognitive dysfunction.

Cannabinoids ameliorate impairments induced by chronic stress to synaptic plasticity and short-term memory.

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Abush, Hila; Akirav, Irit

2013-07-01

Repeated stress is one of the environmental factors that precipitates and exacerbates mental illnesses like depression and anxiety as well as cognitive impairments. We have previously shown that cannabinoids can prevent the effects of acute stress on learning and memory. Here we aimed to find whether chronic cannabinoid treatment would alleviate the long-term effects of exposure to chronic restraint stress on memory and plasticity as well as on behavioral and neuroendocrine measures of anxiety and depression. Late adolescent rats were exposed to chronic restraint stress for 2 weeks followed each day by systemic treatment with vehicle or with the CB1/2 receptor agonist WIN55,212-2 (1.2 mg/kg). Thirty days after the last exposure to stress, rats demonstrated impaired long-term potentiation (LTP) in the ventral subiculum-nucleus accumbens (NAc) pathway, impaired performance in the prefrontal cortex (PFC)-dependent object-recognition task and the hippocampal-dependent spatial version of this task, increased anxiety levels, and significantly reduced expression of glucocorticoid receptors (GRs) in the amygdala, hippocampus, PFC, and NAc. Chronic WIN55,212-2 administration prevented the stress-induced impairment in LTP levels and in the spatial task, with no effect on stress-induced alterations in unconditioned anxiety levels or GR levels. The CB1 antagonist AM251 (0.3 mg/kg) prevented the ameliorating effects of WIN55,212-2 on LTP and short-term memory. Hence, the beneficial effects of WIN55,212-2 on memory and plasticity are mediated by CB1 receptors and are not mediated by alterations in GR levels in the brain areas tested. Our findings suggest that cannabinoid receptor activation could represent a novel approach to the treatment of cognitive deficits that accompany a variety of stress-related neuropsychiatric disorders.

Targeting the Microbiota-Gut-Brain Axis: Prebiotics Have Anxiolytic and Antidepressant-like Effects and Reverse the Impact of Chronic Stress in Mice.

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Burokas, Aurelijus; Arboleya, Silvia; Moloney, Rachel D; Peterson, Veronica L; Murphy, Kiera; Clarke, Gerard; Stanton, Catherine; Dinan, Timothy G; Cryan, John F

2017-10-01

The realization that the microbiota-gut-brain axis plays a critical role in health and disease, including neuropsychiatric disorders, is rapidly advancing. Nurturing a beneficial gut microbiome with prebiotics, such as fructo-oligosaccharides (FOS) and galacto-oligosaccharides (GOS), is an appealing but underinvestigated microbiota manipulation. Here we tested whether chronic prebiotic treatment modifies behavior across domains relevant to anxiety, depression, cognition, stress response, and social behavior. C57BL/6J male mice were administered FOS, GOS, or a combination of FOS+GOS for 3 weeks prior to testing. Plasma corticosterone, microbiota composition, and cecal short-chain fatty acids were measured. In addition, FOS+GOS- or water-treated mice were also exposed to chronic psychosocial stress, and behavior, immune, and microbiota parameters were assessed. Chronic prebiotic FOS+GOS treatment exhibited both antidepressant and anxiolytic effects. Moreover, the administration of GOS and the FOS+GOS combination reduced stress-induced corticosterone release. Prebiotics modified specific gene expression in the hippocampus and hypothalamus. Regarding short-chain fatty acid concentrations, prebiotic administration increased cecal acetate and propionate and reduced isobutyrate concentrations, changes that correlated significantly with the positive effects seen on behavior. Moreover, FOS+GOS reduced chronic stress-induced elevations in corticosterone and proinflammatory cytokine levels and depression-like and anxiety-like behavior in addition to normalizing the effects of stress on the microbiota. Taken together, these data strongly suggest a beneficial role of prebiotic treatment for stress-related behaviors. These findings strengthen the evidence base supporting therapeutic targeting of the gut microbiota for brain-gut axis disorders, opening new avenues in the field of nutritional neuropsychopharmacology. Copyright © 2017 Society of Biological Psychiatry. Published by

Interaction of CD38 Variant and Chronic Interpersonal Stress Prospectively Predicts Social Anxiety and Depression Symptoms Over Six Years

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Tabak, Benjamin A.; Vrshek-Schallhorn, Suzanne; Zinbarg, Richard E.; Prenoveau, Jason M.; Mineka, Susan; Redei, Eva E.; Adam, Emma K.; Craske, Michelle G.

2015-01-01

Variation in the CD38 gene, which regulates secretion of the neuropeptide oxytocin, has been associated with several social phenotypes. Specifically, rs3796863 A allele carriers have demonstrated increased social sensitivity. In 400 older adolescents, we used trait-state-occasion modeling to investigate how rs3796863 genotype, baseline ratings of chronic interpersonal stress, and their gene-environment (GxE) interaction predicted trait social anxiety and depression symptoms over six years. We found significant GxE effects for CD38 A-carrier genotypes and chronic interpersonal stress at baseline predicting greater social anxiety and depression symptoms. A significant GxE effect of smaller magnitude was also found for C/C genotype and chronic interpersonal stress predicting greater depression; however, this effect was small compared to the main effect of chronic interpersonal stress. Thus, in the context of chronic interpersonal stress, heightened social sensitivity associated with the rs3796863 A allele may prospectively predict risk for social anxiety and (to a lesser extent) depression. PMID:26958455

Chronic social stress leads to altered sleep homeostasis in mice.

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Olini, Nadja; Rothfuchs, Iru; Azzinnari, Damiano; Pryce, Christopher R; Kurth, Salome; Huber, Reto

2017-06-01

Disturbed sleep and altered sleep homeostasis are core features of many psychiatric disorders such as depression. Chronic uncontrollable stress is considered an important factor in the development of depression, but little is known on how chronic stress affects sleep regulation and sleep homeostasis. We therefore examined the effects of chronic social stress (CSS) on sleep regulation in mice. Adult male C57BL/6 mice were implanted for electrocortical recordings (ECoG) and underwent either a 10-day CSS protocol or control handling (CON). Subsequently, ECoG was assessed across a 24-h post-stress baseline, followed by a 4-h sleep deprivation, and then a 20-h recovery period. After sleep deprivation, CSS mice showed a blunted increase in sleep pressure compared to CON mice, as measured using slow wave activity (SWA, electroencephalographic power between 1-4Hz) during non-rapid eye movement (NREM) sleep. Vigilance states did not differ between CSS and CON mice during post-stress baseline, sleep deprivation or recovery, with the exception of CSS mice exhibiting increased REM sleep during recovery sleep. Behavior during sleep deprivation was not affected by CSS. Our data provide evidence that CSS alters the homeostatic regulation of sleep SWA in mice. In contrast to acute social stress, which results in a faster SWA build-up, CSS decelerates the homeostatic build up. These findings are discussed in relation to the causal contribution of stress-induced sleep disturbance to depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic Stress Reduces Nectin-1 mRNA Levels and Disrupts Dendritic Spine Plasticity in the Adult Mouse Perirhinal Cortex

Directory of Open Access Journals (Sweden)

Qian Gong

2018-03-01

Full Text Available In adulthood, chronic exposure to stressful experiences disrupts synaptic plasticity and cognitive function. Previous studies have shown that perirhinal cortex-dependent object recognition memory is impaired by chronic stress. However, the stress effects on molecular expression and structural plasticity in the perirhinal cortex remain unclear. In this study, we applied the chronic social defeat stress (CSDS paradigm and measured the mRNA levels of nectin-1, nectin-3 and neurexin-1, three synaptic cell adhesion molecules (CAMs implicated in the adverse stress effects, in the perirhinal cortex of wild-type (WT and conditional forebrain corticotropin-releasing hormone receptor 1 conditional knockout (CRHR1-CKO mice. Chronic stress reduced perirhinal nectin-1 mRNA levels in WT but not CRHR1-CKO mice. In conditional forebrain corticotropin-releasing hormone conditional overexpression (CRH-COE mice, perirhinal nectin-1 mRNA levels were also reduced, indicating that chronic stress modulates nectin-1 expression through the CRH-CRHR1 system. Moreover, chronic stress altered dendritic spine morphology in the main apical dendrites and reduced spine density in the oblique apical dendrites of perirhinal layer V pyramidal neurons. Our data suggest that chronic stress disrupts cell adhesion and dendritic spine plasticity in perirhinal neurons, which may contribute to stress-induced impairments of perirhinal cortex-dependent memory.

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

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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. Copyright © 2016 ISDN. Published by Elsevier Ltd. All rights reserved.

Effects of chronic mild stress on the development of drug dependence in rats.

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Papp, Mariusz; Gruca, Piotr; Lason-Tyburkiewicz, Magdalena; Litwa, Ewa; Willner, Paul

2014-09-01

There is high comorbidity between depression and addiction. Features of addiction relevant to depression have been studied extensively, but less is known about features of depression relevant to addiction. Here, we have studied the effects of chronic mild stress (CMS), a valid animal model of depression, on measures of physical and psychological dependence resulting from subchronic treatment of rats with three drugs of abuse that act through disparate neurobiological mechanisms: morphine, nicotine and diazepam. In animals not treated subchronically with drugs of abuse, CMS increased the withdrawal-like effects of the opiate antagonist naloxone, but not those of the nicotinic antagonist mecamylamine or the benzodiazepine antagonist flumazenil. In animals treated subchronically with drugs of abuse, CMS exacerbated, precipitated and conditioned withdrawal effects associated with all three antagonists. CMS also potentiated withdrawal-induced and cue-induced place aversions associated with all three antagonists. All of the effects of CMS were reversed by chronic treatment with the specific serotonin reuptake inhibitor citalopram. These results suggest that treatment of comorbid depression, although not a primary treatment for addiction, may facilitate other treatments for addiction, by decreasing the severity of withdrawal symptoms and the likelihood of relapse.

A Daily Diary Approach to the Examination of Chronic Stress, Daily Hassles and Safety Perceptions in Hospital Nursing.

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Louch, Gemma; O'Hara, Jane; Gardner, Peter; O'Connor, Daryl B

2017-12-01

Stress is a significant concern for individuals and organisations. Few studies have explored stress, burnout and patient safety in hospital nursing on a daily basis at the individual level. This study aimed to examine the effects of chronic stress and daily hassles on safety perceptions, the effect of chronic stress on daily hassles experienced and chronic stress as a potential moderator. Utilising a daily diary design, 83 UK hospital nurses completed three end-of-shift diaries, yielding 324 person days. Hassles, safety perceptions and workplace cognitive failure were measured daily, and a baseline questionnaire included a measure of chronic stress. Hierarchical multivariate linear modelling was used to analyse the data. Higher chronic stress was associated with more daily hassles, poorer perceptions of safety and being less able to practise safely, but not more workplace cognitive failure. Reporting more daily hassles was associated with poorer perceptions of safety, being less able to practise safely and more workplace cognitive failure. Chronic stress did not moderate daily associations. The hassles reported illustrate the wide-ranging hassles nurses experienced. The findings demonstrate, in addition to chronic stress, the importance of daily hassles for nurses' perceptions of safety and the hassles experienced by hospital nurses on a daily basis. Nurses perceive chronic stress and daily hassles to contribute to their perceptions of safety. Measuring the number of daily hassles experienced could proactively highlight when patient safety threats may arise, and as a result, interventions could usefully focus on the management of daily hassles.

Effects of Chronic Social Defeat Stress on Sleep and Circadian Rhythms Are Mitigated by Kappa-Opioid Receptor Antagonism.

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Wells, Audrey M; Ridener, Elysia; Bourbonais, Clinton A; Kim, Woori; Pantazopoulos, Harry; Carroll, F Ivy; Kim, Kwang-Soo; Cohen, Bruce M; Carlezon, William A

2017-08-09

Stress plays a critical role in the neurobiology of mood and anxiety disorders. Sleep and circadian rhythms are affected in many of these conditions. Here we examined the effects of chronic social defeat stress (CSDS), an ethological form of stress, on sleep and circadian rhythms. We exposed male mice implanted with wireless telemetry transmitters to a 10 day CSDS regimen known to produce anhedonia (a depressive-like effect) and social avoidance (an anxiety-like effect). EEG, EMG, body temperature, and locomotor activity data were collected continuously during the CSDS regimen and a 5 day recovery period. CSDS affected numerous endpoints, including paradoxical sleep (PS) and slow-wave sleep (SWS), as well as the circadian rhythmicity of body temperature and locomotor activity. The magnitude of the effects increased with repeated stress, and some changes (PS bouts, SWS time, body temperature, locomotor activity) persisted after the CSDS regimen had ended. CSDS also altered mRNA levels of the circadian rhythm-related gene mPer2 within brain areas that regulate motivation and emotion. Administration of the κ-opioid receptor (KOR) antagonist JDTic (30 mg/kg, i.p.) before CSDS reduced stress effects on both sleep and circadian rhythms, or hastened their recovery, and attenuated changes in mPer2 Our findings show that CSDS produces persistent disruptions in sleep and circadian rhythmicity, mimicking attributes of stress-related conditions as they appear in humans. The ability of KOR antagonists to mitigate these disruptions is consistent with previously reported antistress effects. Studying homologous endpoints across species may facilitate the development of improved treatments for psychiatric illness. SIGNIFICANCE STATEMENT Stress plays a critical role in the neurobiology of mood and anxiety disorders. We show that chronic social defeat stress in mice produces progressive alterations in sleep and circadian rhythms that resemble features of depression as it appears in

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

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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

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

OpenAIRE

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

2009-01-01

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

The Community Child Health Network Life Stress Interview: a brief chronic stress measure for community health research.

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Tanner Stapleton, Lynlee R; Dunkel Schetter, Christine; Dooley, Larissa N; Guardino, Christine M; Huynh, Jan; Paek, Cynthia; Clark-Kauffman, Elizabeth; Schafer, Peter; Woolard, Richard; Lanzi, Robin Gaines

2016-07-01

Chronic stress is implicated in many theories as a contributor to a wide range of physical and mental health problems. The current study describes the development of a chronic stress measure that was based on the UCLA Life Stress Interview (LSI) and adapted in collaboration with community partners for use in a large community health study of low-income, ethnically diverse parents of infants in the USA (Community Child Health Network [CCHN]). We describe the instrument, its purpose and adaptations, implementation, and results of a reliability study in a subsample of the larger study cohort. Interviews with 272 mothers were included in the present study. Chronic stress was assessed using the CCHN LSI, an instrument designed for administration by trained community interviewers to assess four domains of chronic stress, each rated by interviewers. Significant correlations ranging from small to moderate in size between chronic stress scores on this measure, other measures of stress, biomarkers of allostatic load, and mental health provide initial evidence of construct and concurrent validity. Reliability data for interviewer ratings are also provided. This relatively brief interview (15 minutes) is available for use and may be a valuable tool for researchers seeking to measure chronic stress reliably and validly in future studies with time constraints.

Effect of chronic mild stress on hippocampal transcriptome in mice selected for high and low stress-induced analgesia and displaying different emotional behaviors.

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Lisowski, Pawel; Juszczak, Grzegorz R; Goscik, Joanna; Wieczorek, Marek; Zwierzchowski, Lech; Swiergiel, Artur H

2011-01-01

There is increasing evidence that mood disorders may derive from the impact of environmental pressure on genetically susceptible individuals. Stress-induced hippocampal plasticity has been implicated in depression. We studied hippocampal transcriptomes in strains of mice that display high (HA) and low (LA) swim stress-induced analgesia and that differ in emotional behaviors and responses to different classes of antidepressants. Chronic mild stress (CMS) affected expression of a number of genes common for both strains. CMS also produced strain specific changes in expression suggesting that hippocampal responses to stress depend on genotype. Considerably larger number of genes, biological processes, molecular functions, biochemical pathways, and gene networks were affected by CMS in LA than in HA mice. The results suggest that potential drug targets against detrimental effects of stress include glutamate transporters, and cholinergic, cholecystokinin (CCK), glucocorticoids, and thyroid hormones receptors. Furthermore, some biological processes evoked by stress and different between the strains, such as apoptosis, neurogenesis and chromatin modifications, may be responsible for the long-term, irreversible effects of stress and suggest a role for epigenetic regulation of mood related stress responses. Copyright © 2010 Elsevier B.V. and ECNP. All rights reserved.

The effect of basolateral amygdala nucleus lesion on memory under acute,mid and chronic stress in male rats.

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Ranjbar, Hoda; Radahmadi, Maryam; Alaei, Hojjatallah; Reisi, Parham; Karimi, Sara

2016-12-20

The basolateral amygdala (BLA) modulates memory for emotional events and is involved in both stress and memory. This study investigated different durations of stress and the role of BLA on serum corticosterone level and spatial and cognitive memory. Different durations of stress (acute, mid, and chronic stress), with and without BLA lesion were induced in rats by 6 h/day restraint stress for 1, 7, and 21 days. Memory functions were evaluated by novel object recognition (NOR) and object location test (OLT). The OLT findings showed locomotor activity and spatial memory slightly decreased with different durations of stress. The NOR findings significantly showed locomotor activity impairment in different durations of stress. Cognitive memory deficit was observed in mid stress. The corticosterone level significantly increased in the mid and chronic stress groups. Moreover, the mid stress was the strongest stress condition. There is a possibility that different stress durations act by different mechanisms. The recognition of a novel location decreased in all lesion groups. It was more severe in the NOR. The BLA lesion significantly decreased corticosterone level in the mid and chronic stress groups compared to similar groups without lesion. The BLA lesion caused more damage to cognitive than spatial memory in stressed groups.

VR Mobile Solutions For Chronic Stress Reduction in Young Adults.

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Gao, Kenneth; Boyd, Chelsie; Wiederhold, Mark D; Wiederhold, Brenda K

2014-01-01

Chronic stress in young adults has become a growing problem within recent decades and many are unable to find cost-effective and accessible treatment for psychological stress in their daily lives. We analyze the market of using a mobile application, Positive Technology, as a solution. Eleven participants, aged between 18 and 24, participated in the exercise. Self-reported stress reduction was measured via an online marketing survey, while physiological measurements were monitored via peripheral devices. Secondary goals assessed the app's ease-of-use, accessibility, and cost. Results indicate that participants enjoyed the availability of the mobile solution and found the app to be fun and easy to learn. Stress levels were reduced in 73% of the participants, with higher effects in females and in participants aged 18-24. We conclude that the mobile platform is an effective means of delivering psychological stress reduction, and could provide an accessible, cost-effective solution.

Impaired Latent Inhibition in GDNF-Deficient Mice Exposed to Chronic Stress

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Mona Buhusi

2017-10-01

Full Text Available Increased reactivity to stress is maladaptive and linked to abnormal behaviors and psychopathology. Chronic unpredictable stress (CUS alters catecholaminergic neurotransmission and remodels neuronal circuits involved in learning, attention and decision making. Glial-derived neurotrophic factor (GDNF is essential for the physiology and survival of dopaminergic neurons in substantia nigra and of noradrenergic neurons in the locus coeruleus. Up-regulation of GDNF expression during stress is linked to resilience; on the other hand, the inability to up-regulate GDNF in response to stress, as a result of either genetic or epigenetic modifications, induces behavioral alterations. For example, GDNF-deficient mice exposed to chronic stress exhibit alterations of executive function, such as increased temporal discounting. Here we investigated the effects of CUS on latent inhibition (LI, a measure of selective attention and learning, in GDNF-heterozygous (HET mice and their wild-type (WT littermate controls. No differences in LI were found between GDNF HET and WT mice under baseline experimental conditions. However, following CUS, GDNF-deficient mice failed to express LI. Moreover, stressed GDNF-HET mice, but not their WT controls, showed decreased neuronal activation (number of c-Fos positive neurons in the nucleus accumbens shell and increased activation in the nucleus accumbens core, both key regions in the expression of LI. Our results add LI to the list of behaviors affected by chronic stress and support a role for GDNF deficits in stress-induced pathological behaviors relevant to schizophrenia and other psychiatric disorders.

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

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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.

Effects of stress on alcohol drinking: a review of animal studies

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Lopez, Marcelo F.; Doremus-Fitzwater, Tamara L.

2011-01-01

Rationale While stress is often proposed to play a significant role in influencing alcohol consumption, the relationship between stress and alcohol is complex and poorly understood. Over several decades, stress effects on alcohol drinking have been studied using a variety of animal models and experimental procedures, yet this large body of literature has generally produced equivocal results. Objectives This paper reviews results from animal studies in which alcohol consumption is evaluated under conditions of acute/sub-chronic stress exposure or models of chronic stress exposure. Evidence also is presented indicating that chronic intermittent alcohol exposure serves as a stressor that consequently influences drinking. Results The effects of various acute/sub-chronic stress procedures on alcohol consumption have generally been mixed, but most study outcomes suggest either no effect or decreased alcohol consumption. In contrast, most studies indicate that chronic stress, especially when administered early in development, results in elevated drinking later in adulthood. Chronic alcohol exposure constitutes a potent stressor itself, and models of chronic intermittent alcohol exposure reliably produce escalation of voluntary alcohol consumption. Conclusions A complex and dynamic interplay among a wide array of genetic, biological, and environmental factors govern stress responses, regulation of alcohol drinking, and the circumstances in which stress modulates alcohol consumption. Suggestions for future directions and new approaches are presented that may aid in developing more sensitive and valid animal models that not only better mimic the clinical situation, but also provide greater understanding of mechanisms that underlie the complexity of stress effects on alcohol drinking. PMID:21850445

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

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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.

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus).

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Lattin, Christine R; Romero, L Michael

2014-07-15

The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. © 2014. Published by The Company of Biologists Ltd.

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…

Opposite effects of glucocorticoid receptor activation on hippocampal CA1 dendritic complexity in chronically stressed and handled animals

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Alfarez, D.N.; Karst, H.; Velzing, E.H.; Joëls, M.; Krugers, H.J.

2008-01-01

Remodeling of synaptic networks is believed to contribute to synaptic plasticity and long-term memory performance, both of which are modulated by chronic stress. We here examined whether chronic stress modulates dendritic complexity of hippocampal CA1 pyramidal cells, under conditions of basal as

Implications of red Panax ginseng in oxidative stress associated chronic diseases

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Yoon-Mi Lee

2017-04-01

Full Text Available The steaming process of Panax ginseng has been reported to increase its major known bioactive components, ginsenosides, and, therefore, its biological properties as compared to regular Panax ginseng. Biological functions of red Panax ginseng attenuating pro-oxidant environments associated with chronic diseases are of particular interest, since oxidative stress can be a key contributor to the pathogenesis of chronic diseases. Additionally, proper utilization of various biomarkers for evaluating antioxidant activities in natural products, such as ginseng, can also be important to providing validity to their activities. Thus, studies on the effects of red ginseng against various diseases as determined in cell lines, animal models, and humans were reviewed, along with applied biomarkers for verifying such effects. Limitations and future considerations of studying red ginseng were been discussed. Although further clinical studies are warranted, red ginseng appears to be beneficial for attenuating disease-associated symptoms via its antioxidant activities, as well as for preventing oxidative stress-associated chronic diseases.

Effects of chronic restraint stress and estradiol on open field activity, spatial memory, and monoaminergic neurotransmitters in ovariectomized rats.

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Bowman, R E; Ferguson, D; Luine, V N

2002-01-01

Twenty-one days of chronic restraint stress impairs male rat performance on the radial arm maze [Luine et al. (1994) Brain Res. 639, 167-170], but enhances female rat performance [Bowman et al. (2001) Brain Res. 904, 279-289]. To assess possible ovarian hormone mechanisms underlying this sexually dimorphic response to stress, we examined chronic stress effects in ovariectomized rats. Ovariectomized rats received Silastic capsule implants containing cholesterol or estradiol and were assigned to a daily restraint stress (21 days, 6 h/day) or non-stress group. Following the stress period, subjects were tested for open field activity and radial arm maze performance. Stress and estradiol treatment affected open field activity. All stressed animals, with or without estradiol treatment, made fewer total outer sector crossings. In contrast, estradiol-treated animals, with or without stress, made more inner sector visits, an indication that estradiol decreased anxious behavior on the open field across time. As measured by the total number of visits required to complete the task, stress did not affect radial arm maze performance in ovariectomized rats, but estradiol-treated animals, with or without stress, performed better than non-treated animals on the radial arm maze. Stressed subjects receiving estradiol showed the best radial arm maze performance. Following killing, tissue samples were obtained from various brain regions known to contribute to learning and memory, and monoamine and metabolite levels were measured. Several changes were observed in response to both stress and estradiol. Most noteworthy, stress treatment decreased homovanillic acid levels in the prefrontal cortex, an effect not previously observed in stressed intact females. Estradiol treatment increased norepinephrine levels in CA3 region of the hippocampus, mitigating stress-dependent changes. Both stress and estradiol decreased dentate gyrus levels of 5-hydroxyindole acetic acid. In summary, the current

Protective effects of chronic mild stress during adolescence in the low-novelty responder rat.

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Rana, Samir; Nam, Hyungwoo; Glover, Matthew E; Akil, Huda; Watson, Stanley J; Clinton, Sarah M; Kerman, Ilan A

2016-01-01

Stress-elicited behavioral and physiologic responses vary widely across individuals and depend on a combination of environmental and genetic factors. Adolescence is an important developmental period when neural circuits that guide emotional behavior and stress reactivity are still maturing. A critical question is whether stress exposure elicits contrasting effects when it occurs during adolescence versus adulthood. We previously found that Sprague-Dawley rats selectively bred for low-behavioral response to novelty (bred Low Responders; bLRs) are particularly sensitive to chronic unpredictable mild stress (CMS) exposure in adulthood, which exacerbates their typically high levels of spontaneous depressive- and anxiety-like behavior. Given developmental processes known to occur during adolescence, we sought to determine whether the impact of CMS on bLR rats is equivalent when they are exposed to it during adolescence as compared with adulthood. Young bLR rats were either exposed to CMS or control condition from postnatal days 35-60. As adults, we found that CMS-exposed bLRs maintained high levels of sucrose preference and exhibited increased social exploration along with decreased immobility on the forced swim test compared with bLR controls. These data indicate a protective effect of CMS exposure during adolescence in bLR rats.

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

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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

Impact of chronic maternal stress during early gestation on maternal-fetal stress transfer and fetal stress sensitivity in sheep.

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Dreiling, Michelle; Schiffner, Rene; Bischoff, Sabine; Rupprecht, Sven; Kroegel, Nasim; Schubert, Harald; Witte, Otto W; Schwab, Matthias; Rakers, Florian

2018-01-01

Acute stress-induced reduction of uterine blood flow (UBF) is an indirect mechanism of maternal-fetal stress transfer during late gestation. Effects of chronic psychosocial maternal stress (CMS) during early gestation, as may be experienced by many working women, on this stress signaling mechanism are unclear. We hypothesized that CMS in sheep during early gestation augments later acute stress-induced decreases of UBF, and aggravates the fetal hormonal, cardiovascular, and metabolic stress responses during later development. Six pregnant ewes underwent repeated isolation stress (CMS) between 30 and 100 days of gestation (dGA, term: 150 dGA) and seven pregnant ewes served as controls. At 110 dGA, ewes were chronically instrumented and underwent acute isolation stress. The acute stress decreased UBF by 19% in both the CMS and control groups (p stress-induced cortisol and norepinephrine concentrations indicating a hyperactive hypothalamus-pituitary-adrenal (HPA)-axis and sympathetic-adrenal-medullary system. Increased fetal norepinephrine is endogenous as maternal catecholamines do not cross the placenta. Cortisol in the control but not in the CMS fetuses was correlated with maternal cortisol blood concentrations; these findings indicate: (1) no increased maternal-fetal cortisol transfer with CMS, (2) cortisol production in CMS fetuses when the HPA-axis is normally inactive, due to early maturation of the fetal HPA-axis. CMS fetuses were better oxygenated, without shift towards acidosis compared to the controls, potentially reflecting adaptation to repeated stress. Hence, CMS enhances maternal-fetal stress transfer by prolonged reduction in UBF and increased fetal HPA responsiveness.

Effects of Chronic Interpersonal Stress Exposure on Depressive Symptoms are Moderated by Genetic Variation at IL6 and IL1β in Youth

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Tartter, Margaret; Hammen, Constance; Bower, Julienne E.; Brennan, Patricia A.; Cole, Steven

2015-01-01

Aims Close to one third of patients with major depression show increases in pro-inflammatory cytokines, which are in turn associated with risk for inflammatory disease. Genetic variants that enhance immune reactivity may thus enhance inflammatory and depressive reactions to stress. The aim of the present study was to investigate a trio of functional SNPs in the promoter regions of IL6 (-174G>C, rs1800795), IL1β (-511C>T, rs16944), and TNF (-308G>A, rs1800629) as moderators of the relationship between chronic stress exposure and elevations in depressive symptoms. Methods Participants were 444 Australian youth (mean age = 20.12) whose exposure to chronic stress in the past 6 months was assessed using the semi-structured UCLA Life Stress Interview, and who completed the Beck Depression Inventory II at ages 15 and 20. Between ages 22 and 25, all participants in the selected sample provided blood samples for genotyping. Results In line with a hypothesized moderation effect, -174G allele carriers at IL6 had fewer depressive symptoms following interpersonal stress, relative to C/C homozygotes with equal interpersonal stress exposure. However, IL6 genotype did not moderate the effects of non-interpersonal stress exposure (i.e., financial, work and health-related difficulties) on depression. Also in line with hypotheses, the -511C allele in IL1β, previously associated with higher IL-1β expression, was associated with more severe depression following chronic interpersonal stress exposure, relative to T/T homozygotes. Again, the moderating effect was specific to interpersonal stressors and did not generalize to non-interpersonal stress. TNF was not a moderator of the effects of either interpersonal or non-interpersonal stress on later depression outcomes. Conclusion Findings were consistent with the hypothesis that pro-inflammatory genetic variation increases the risk of stress-induced depression. The present results provide evidence of a genetic mechanism contributing to

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

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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. Copyright © 2012 Elsevier B.V. All rights reserved.

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

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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.

Effects of acute and chronic stress on telencephalic neurochemistry and gene expression in rainbow trout (Oncorhynchus mykiss)

DEFF Research Database (Denmark)

Moltesen, Maria; Laursen, Danielle Caroline; Thörnqvist, Per Ove

2016-01-01

By filtering relevant sensory inputs and initiating stress responses, the brain is an essential organ in stress coping and adaptation. However, exposure to chronic or repeated stress can lead to allostatic overload, where neuroendocrinal and behavioral reactions to stress become maladaptive. This...

Protective effect of epigallocatechin gallate in murine water-immersion stress model of chronic fatigue syndrome.

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Sachdeva, Anand Kamal; Kuhad, Anurag; Tiwari, Vinod; Arora, Vipin; Chopra, Kanwaljit

2010-06-01

Chronic fatigue syndrome (CFS) is a specific clinical condition that characterizes unexplained disabling fatigue. In the present study, chronic fatigue was produced in mice by subjecting them to forced swim inside a rectangular jar of specific dimensions for 6 min. daily for 15 days. Epigallocatechin gallate (EGCG; 25, 50 and 100 mg/kg, p.o.) was administered daily 30 min. before forced swim session. Immobility period and post-swim fatigue was assessed on alternate days. On the 16th day, after assessment of various behavioural parameters, mice were killed to harvest the brain, spleen and thymus. There was significant increase in oxidative-nitrosative stress and tumour necrosis factor-alpha levels in the brain of mice subjected to water-immersion stress as compared with naive group. These behavioural and biochemical alterations were restored after chronic treatment with EGCG. The present study points out that EGCG could be of therapeutic potential in the treatment of chronic fatigue.

Exacerbation of N-nitrosodiethylamine Induced Hepatotoxicity and DNA Damage in Mice Exposed to Chronic Unpredictable Stress

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Nayeem Bilal

2017-06-01

Full Text Available Psychological stress contributes to increased susceptibility to a number of diseases including cancer. The present study was designed to assess the effect of chronic unpredictable stress on N-nitrosodiethylamine induced liver toxicity in terms of in vivo antioxidant status and DNA damage in Swiss albino mice. The animals used in this study were randomized into different groups based on the treatment with N-nitrosodiethylamine or chronic unpredictable stress alone and post-stress administration of N-nitrosodiethylamine. The mice were sacrificed after 12 weeks of treatment, and the status of major enzymatic and non-enzymatic antioxidants, liver function markers, lipid peroxidation and the extent of DNA damage were determined in circulation and liver tissues of all the groups. The N-nitrosodiethylamine treated group showed significantly compromised levels of the antioxidant enzymes, lipid peroxidation, and the liver function markers with enhanced DNA damage as compared to chronic unpredictable stress or control groups. A similar but less typical pattern observed in the chronic unpredictable stress treated mice. All the measured biochemical parameters were significantly altered in the group treated with the combination of chronic unpredictable stress and N-nitrosodiethylamine when compared to controls, or chronic unpredictable stress alone and/or N-nitrosodiethylamine alone treated groups. Thus, exposure to continuous, unpredictable stress conditions even in general life may significantly enhance the hepatotoxic potential of N-nitrosodiethylamine through an increase in the oxidative stress and DNA damage.

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

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

2015-08-01

Large individual differences in adolescent mental health following chronic psychosocial stress suggest moderating factors. We examined two established moderators, basal cortisol and parental psychiatric history, simultaneously. We hypothesized that individuals with high basal cortisol, assumed to indicate high context sensitivity, would show relatively high problem levels following chronic stress, especially in the presence of parental psychiatric history. With Linear Mixed Models, we investigated the hypotheses in 1917 Dutch adolescents (53.2% boys), assessed at ages 11, 13.5, and 16. Low basal cortisol combined with the absence of a parental psychiatric history increased the risk of externalizing but not internalizing problems following chronic stress. Conversely, low basal cortisol combined with a substantial parental psychiatric history increased the risk of internalizing but not externalizing problems following chronic stress. Thus, parental psychiatric history moderated stress- cortisol interactions in predicting psychopathology, but in a different direction than hypothesized. We conclude that the premise that basal cortisol indicates context sensitivity may be too crude. Context sensitivity may not be a general trait but may depend on the nature of the context (e.g., type or duration of stress exposure) and on the outcome of interest (e.g., internalizing vs. externalizing problems). Although consistent across informants, our findings need replication.

Are there associations between sleep bruxism, chronic stress, and sleep quality?

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Ohlmann, Brigitte; Bömicke, Wolfgang; Habibi, Yasamin; Rammelsberg, Peter; Schmitter, Marc

2018-07-01

The purpose of this study was to identify associations between definite sleep bruxism, as defined by the American academy of sleep medicine, and chronic stress and sleep quality. Sleep bruxism was determined by use of questionnaires, assessment of clinical symptoms, and recording of electromyographic and electrocardiographic data (recorded by the Bruxoff ® device). The study included 67 participants. Of these, 38 were identified as bruxers and 29 as non-bruxers. The 38 bruxers were further classified as 17 moderate and 21 intense bruxers. Self-reported stress and self-reported sleep quality were determined by use of the validated questionnaires "Trier Inventory for the Assessment of Chronic Stress" (TICS) and the "Pittsburgh Sleep Quality Index" (PSQI). No statistically significant association was found between sleep bruxism and self-reported stress or sleep quality. However, a significant association between specific items of chronic stress and poor sleep quality was identified. The results of this study indicate an association between subjective sleep quality and subjective chronic stress, irrespective of the presence or absence of sleep bruxism. Chronic stress and sleep quality do not seem to be associated with sleep bruxism. (clinical trial no. NCT03039985). Copyright © 2018 Elsevier Ltd. All rights reserved.

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

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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. Copyright © 2013 Elsevier Inc. All rights reserved.

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

OpenAIRE

Sibille, Kimberly T; Langaee, Taimour; Burkley, Ben; Gong, Yan; Glover, Toni L; King, Chris; Riley, Joseph L; Leeuwenburgh, Christiaan; Staud, Roland; Bradley, Laurence A; Fillingim, Roger B

2012-01-01

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...

[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.

Individual differences in the effects of chronic stress on memory: behavioral and neurochemical correlates of resiliency.

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Sweis, B M; Veverka, K K; Dhillon, E S; Urban, J H; Lucas, L R

2013-08-29

Chronic stress has been shown to impair memory, however, the extent to which memory can be impaired is often variable across individuals. Predisposed differences in particular traits, such as anxiety, may reveal underlying neurobiological mechanisms that could be driving individual differences in sensitivity to stress and, thus, stress resiliency. Such pre-morbid characteristics may serve as early indicators of susceptibility to stress. Neuropeptide Y (NPY) and enkephalin (ENK) are neurochemical messengers of interest implicated in modulating anxiety and motivation circuitry; however, little is known about how these neuropeptides interact with stress resiliency and memory. In this experiment, adult male rats were appetitively trained to locate sugar rewards in a motivation-based spatial memory task before undergoing repeated immobilization stress and then being tested for memory retention. Anxiety-related behaviors, among other characteristics, were monitored longitudinally. Results indicated that stressed animals which showed little to no impairments in memory post-stress (i.e., the more stress-resilient individuals) exhibited lower anxiety levels prior to stress when compared to stressed animals that showed large deficits in memory (i.e., the more stress-susceptible individuals). Interestingly, all stressed animals, regardless of memory change, showed reduced body weight gain as well as thymic involution, suggesting that the effects of stress on metabolism and the immune system were dissociated from the effects of stress on higher cognition, and that stress resiliency seems to be domain-specific rather than a global characteristic within an individual. Neurochemical analyses revealed that NPY in the hypothalamus and amygdala and ENK in the nucleus accumbens were modulated differentially between stress-resilient and stress-susceptible individuals, with elevated expression of these neuropeptides fostering anxiolytic and pro-motivation function, thus driving

Chronic restraint stress exacerbates nociception and inflammatory response induced by bee venom in rats: the role of the P2X7 receptors.

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Li, Xiao-Qiu; Li, Man; Zhou, Zhong-He; Liu, Bao-Jun; Chen, Hui-Sheng

2016-02-01

Chronic restraint stress exacerbates pain and inflammation. The present study was designed to evaluate the effect of chronic restraint stress on inflammatory pain induced by subcutaneous injection of bee venom (BV). First, we investigated: (1) the effect of two-week restraint stress with daily 2 or 8 h on the baseline paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL) and paw circumference (PC); (2) the effect of chronic stress on the spontaneous paw-flinching reflex (SPFR), decrease in PWM, PWTL and increase in PC of the injected paw induced by BV. The results showed that (1) chronic restraint decreased significantly the PWMT and inhibited significantly the increase in PC, but had no effect on PWTL, compared with control group; (2) chronic restraint enhanced significantly BV-induced SPFR and inflammatory swelling of the injected paw. In a second series of experiments, the role of P2X7 receptor (P2X7R) in the enhancement of BV-induced inflammatory pain produced by chronic restraint stress was determined. Systemic pretreatment with P2X7R antagonist completely reversed the decrease in PWMT produced by chronic restraint, inhibited significantly the enhancement of BV-induced inflammatory pain produced by chronic restraint stress. Taken together, our data indicate that chronic restraint stress-enhanced nociception and inflammation in the BV pain model, possibly involving the P2X7R.

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

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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.

Maternal separation in early life modifies anxious behavior and Fos and glucocorticoid receptor expression in limbic neurons after chronic stress in rats: effects of tianeptine.

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Trujillo, Verónica; Durando, Patricia E; Suárez, Marta M

2016-01-01

Early-life adversity can lead to long-term consequence persisting into adulthood. Here, we assess the implications of an adverse early environment on vulnerability to stress during adulthood. We hypothesized that the interplay between early and late stress would result in a differential phenotype regarding the number of neurons immunoreactive for glucocorticoid receptor (GR-ir) and neuronal activity as assessed by Fos immunoreactivity (Fos-ir) in brain areas related to stress responses and anxiety-like behavior. We also expected that the antidepressant tianeptine could correct some of the alterations induced in our model. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h during the first 3 weeks of life. As adults, the rats were exposed to chronic stress for 24 d and they were treated daily with tianeptine (10 mg/kg intraperitoneal) or vehicle (isotonic saline). Fos-ir was increased by MS in all structures analyzed. Chronic stress reduced Fos-ir in the hippocampus, but increased it in the paraventricular nucleus. Furthermore, chronic stress increased GR-ir in hippocampus (CA1) and amygdala in control non-MS rats. By contrast, when MS and chronic stress were combined, GR-ir was decreased in these structures. Additionally, whereas tianeptine did not affect Fos-ir, it regulated GR-ir in a region-dependent manner, in hippocampus and amygdala opposing in some cases the stress or MS effects. Furthermore, tianeptine reversed the MS- or stress-induced anxious behavior. The interplay between MS and chronic stress observed indicates that MS rats have a modified phenotype, which is expressed when they are challenged by stress in later life.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

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Duque, Aránzazu; Vinader-Caerols, Concepción; Monleón, Santiago

2017-01-01

We have previously observed the impairing effects of chronic social defeat stress (CSDS) on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL); non-stressed + indomethacin (NS+IND); stressed + saline (S+SAL); and stressed + indomethacin (S+IND). Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS) for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.). 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group) were then evaluated in inhibitory avoidance (IA), novel object recognition (NOR), elevated plus maze and hot plate tests. As in control animals (NS+SAL group), IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group). Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

Indomethacin counteracts the effects of chronic social defeat stress on emotional but not recognition memory in mice.

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Aránzazu Duque

Full Text Available We have previously observed the impairing effects of chronic social defeat stress (CSDS on emotional memory in mice. Given the relation between stress and inflammatory processes, we sought to study the effectiveness of the anti-inflammatory indomethacin in reversing the detrimental effects of CSDS on emotional memory in mice. The effects of CSDS and indomethacin on recognition memory were also evaluated. Male CD1 mice were randomly divided into four groups: non-stressed + saline (NS+SAL; non-stressed + indomethacin (NS+IND; stressed + saline (S+SAL; and stressed + indomethacin (S+IND. Stressed animals were exposed to a daily 10 min agonistic confrontation (CSDS for 20 days. All subjects were treated daily with saline or indomethacin (10 mg/kg, i.p.. 24 h after the CSDS period, all the mice were evaluated in a social interaction test to distinguish between those that were resilient or susceptible to social stress. All subjects (n = 10-12 per group were then evaluated in inhibitory avoidance (IA, novel object recognition (NOR, elevated plus maze and hot plate tests. As in control animals (NS+SAL group, IA learning was observed in the resilient groups, as well as in the susceptible mice treated with indomethacin (S+IND group. Recognition memory was observed in the non-stressed and the resilient mice, but not in the susceptible animals. Also, stressed mice exhibited higher anxiety levels. No significant differences were observed in locomotor activity or analgesia. In conclusion, CSDS induces anxiety in post-pubertal mice and impairs emotional and recognition memory in the susceptible subjects. The effects of CSDS on emotional memory, but not on recognition memory and anxiety, are reversed by indomethacin. Moreover, memory impairment is not secondary to the effects of CSDS on locomotor activity, emotionality or pain sensitivity.

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

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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.

Adolescent environmental enrichment prevents behavioral and physiological sequelae of adolescent chronic stress in female (but not male) rats.

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Smith, Brittany L; Morano, Rachel L; Ulrich-Lai, Yvonne M; Myers, Brent; Solomon, Matia B; Herman, James P

2017-11-22

The late adolescent period is characterized by marked neurodevelopmental and endocrine fluctuations in the transition to early adulthood. Adolescents are highly responsive to the external environment, which enhances their ability to adapt and recover from challenges when given nurturing influences, but also makes them vulnerable to aberrant development when exposed to prolonged adverse situations. Female rats are particularly sensitive to the effects of chronic stress in adolescence, which manifests as passive coping strategies and blunted hypothalamo-pituitary adrenocortical (HPA) stress responses in adulthood. We sought to intervene by exposing adolescent rats to environmental enrichment (EE) immediately prior to and during chronic stress, hypothesizing that EE would minimize or prevent the long-term effects of stress that emerge in adult females. To test this, we exposed male and female rats to EE on postnatal days (PND) 33-60 and implemented chronic variable stress (CVS) on PND 40-60. CVS consisted of twice-daily unpredictable stressors. Experimental groups included: CVS/unenriched, unstressed/EE, CVS/EE and unstressed/unenriched (n = 10 of each sex/group). In adulthood, we measured behavior in the open field test and forced swim test (FST) and collected blood samples following the FST. We found that environmental enrichment given during the adolescent period prevented the chronic stress-induced transition to passive coping in the FST and reversed decreases in peak adrenocortical responsiveness observed in adult females. Adolescent enrichment had little to no effect on males or unstressed females tested in adulthood, indicating that beneficial effects are specific to females that were exposed to chronic stress.

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

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Boyks Marco

2011-04-01

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

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

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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.

5-Hydroxytryptamine-Independent Antidepressant Actions of (R)-Ketamine in a Chronic Social Defeat Stress Model.

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Zhang, Kai; Dong, Chao; Fujita, Yuko; Fujita, Atsuhiro; Hashimoto, Kenji

2018-02-01

Previous reports suggest that 5-hydroxytryptamine might play a role in the antidepressant actions of (R,S)-ketamine. However, its role in the antidepressant actions of (R)-ketamine, which is more potent than (S)-ketamine, is unknown. This study was conducted to examine whether 5-hydroxytryptamine depletion affects the antidepressant actions of (R)-ketamine in a chronic social defeat stress model. An inhibitor of 5-hydroxytryptamine synthesis, para-chlorophenylalanine methyl ester hydrochloride (300 mg/kg, twice daily for 3 consecutive days), or vehicle was administered to control and chronic social defeat stress-susceptible mice. Levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, in mouse brain regions were measured using high-performance liquid chromatography. Furthermore, antidepressant effects of (R)-ketamine (10 mg/kg) in the vehicle- and para-chlorophenylalanine methyl ester hydrochloride-treated susceptible mice were assessed using tail suspension test and 1% sucrose preference test. para-Chlorophenylalanine methyl ester hydrochloride treatment caused marked reductions of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid in the brain regions of control and chronic social defeat stress susceptible mice. In the tail suspension test, (R)-ketamine significantly attenuated the increased immobility time in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. In the sucrose preference test (2 and 5 days after a single dose), (R)-ketamine significantly enhanced reduced sucrose consumption in the chronic social defeat stress-susceptible mice with or without 5-hydroxytryptamine depletion. These findings show that 5-hydroxytryptamine depletion did not affect the antidepressant effects of (R)-ketamine in a chronic social defeat stress model. Therefore, it is unlikely that 5-hydroxytryptamine plays a major role in the antidepressant actions of (R)-ketamine. © The Author 2017. Published by Oxford

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

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Pârvu, Alina Elena; Alb, Sandu Florin; Crăciun, Alexandra; Taulescu, Marian Aurel

2013-02-01

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. 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 (NO(x)) and 3NT. Compared to baseline, at the completion of treatment, significant decreases in the levels of tissue iNOS and 3NT and serum NO(x) 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. 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.

Chronic Stress Facilitates the Development of Deep Venous Thrombosis

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Tao Dong

2015-01-01

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

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

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Kathleen Marie Kokolus

2014-02-01

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

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

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Udi E Ghitza

2016-05-01

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

Chronic parenting stress and mood reactivity: The role of sleep quality.

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da Estrela, Chelsea; Barker, Erin T; Lantagne, Sarah; Gouin, Jean-Philippe

2018-04-01

Sleep is a basic biological process supporting emotion regulation. The emotion regulation function of sleep may be particularly important in the context of chronic stress. To better understand how chronic stress and sleep interact to predict mood, 66 parents of children with autism completed daily diaries assessing parenting stress, negative mood, and sleep quality for 6 consecutive days. Hierarchical linear modelling revealed that daily negative mood was predicted by between-person differences in parenting stress and between-person differences in sleep efficiency. Further, between-person differences in sleep efficiency and within-person differences in sleep satisfaction moderated the impact of stress on mood. These data suggest that sleep disturbances may exacerbate the association between stress and mood in the context of chronic parenting stress. Further, high parenting stress appears to heighten the impact of transient sleep disturbances on mood. Copyright © 2017 John Wiley & Sons, Ltd.

Chronic Stress and Glucocorticoids: From Neuronal Plasticity to Neurodegeneration

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Sheela Vyas

2016-01-01

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

Stress and Sleep Duration Predict Headache Severity in Chronic Headache Sufferers

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

2012-01-01

The objective of this study was to evaluate the time-series relationships between stress, sleep duration, and headache pain among patients with chronic headaches. Sleep and stress have long been recognized as potential triggers of episodic headache (< 15 headache days/month), though prospective evidence is inconsistent and absent in patients diagnosed with chronic headaches (≥ 15 days/month). We reanalyzed data from a 28-day observational study of chronic migraine (n = 33) and chronic tension...

Interactive effects of chronic stress and a high-sucrose diet on nonalcoholic fatty liver in young adult male rats.

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Corona-Pérez, Adriana; Díaz-Muñoz, Mauricio; Cuevas-Romero, Estela; Luna-Moreno, Dalia; Valente-Godínez, Héctor; Vázquez-Martínez, Olivia; Martínez-Gómez, Margarita; Rodríguez-Antolín, Jorge; Nicolás-Toledo, Leticia

2017-11-01

Glucocorticoids have been implicated in nonalcoholic fatty liver diseases (NAFLD). The influence of a palatable diet on the response to stress is controversial. This study explored whether a high-sucrose diet could protect from hepatic steatosis induced by chronic restraint stress in young adult rats. Male Wistar rats aged 21 days were allocated into four groups (n = 6-8 per group): control, chronic restraint stress, 30% sucrose diet, and 30% sucrose diet plus chronic restraint stress. After being exposed to either tap water or sucrose solution during eight weeks, half of the rats belonging to each group were subject or not to repeated restraint stress (1 h per day, 5 days per week) during four weeks. Triacylglycerol (TAG), oxidative stress, activity of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD-1), infiltration of immune cells, and glycogen amount in the liver were quantified. Serum concentrations of corticosterone and testosterone were also measured. The stressed group showed normal serum concentrations of corticosterone and did not have hepatic steatosis. However, this group showed increased glycogen, inflammation, mild fibrosis, oxidative stress, and a high activity of 11β-HSD-1 in the liver. The group exposed to the high-sucrose diet had lower concentrations of corticosterone, hepatic steatosis and moderate fibrosis. The group subject to high-sucrose diet plus chronic restraint stress showed low concentrations of corticosterone, hepatic steatosis, oxidative stress, and high concentrations of testosterone. Thus, restraint stress and a high-sucrose diet each generate different components of nonalcoholic fatty liver in young adult rats. The combination of both the factors could promote a faster development of NAFLD.

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

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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. © The Author(s) 2014.

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

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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

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Hooper, Andrew; Maguire, Jamie

2016-01-01

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 (GABAAR) 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 GABAAR δ subunit expression specifically in dentate gyrus granule cells (Gabrd/Pomc mice). Reduced GABAAR 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 GABAAR δ subunit-mediated tonic inhibition in

The hypothalamic–pituitary–adrenal axis and sex hormones in chronic stress and obesity: pathophysiological and clinical aspects

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Pasquali, Renato

2012-01-01

Obesity, particularly the abdominal phenotype, has been ascribed to an individual maladaptation to chronic environmental stress exposure mediated by a dysregulation of related neuroendocrine axes. Alterations in the control and action of the hypothalamic–pituitary–adrenal axis play a major role in this context, with the participation of the sympathetic nervous system. The ability to adapt to chronic stress may differ according to sex, with specific pathophysiological events leading to the development of stress-related chronic diseases. This seems to be influenced by the regulatory effects of sex hormones, particularly androgens. Stress may also disrupt the control of feeding, with some differences according to sex. Finally, the amount of experimental data in both animals and humans may help to shed more light on specific phenotypes of obesity, strictly related to the chronic exposure to stress. This challenge may potentially imply a different pathophysiological perspective and, possibly, a specific treatment. PMID:22612409

Neurobiology of Chronic Stress-Related Psychiatric Disorders: Evidence from Molecular Imaging Studies

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Davis, Margaret T.; Holmes, Sophie E.; Pietrzak, Robert H.; Esterlis, Irina

2018-01-01

Chronic stress accounts for billions of dollars of economic loss annually in the United States alone, and is recognized as a major source of disability and mortality worldwide. Robust evidence suggests that chronic stress plays a significant role in the onset of severe and impairing psychiatric conditions, including major depressive disorder, bipolar disorder, and posttraumatic stress disorder. Application of molecular imaging techniques such as positron emission tomography and single photon emission computed tomography in recent years has begun to provide insight into the molecular mechanisms by which chronic stress confers risk for these disorders. The present paper provides a comprehensive review and synthesis of all positron emission tomography and single photon emission computed tomography imaging publications focused on the examination of molecular targets in individuals with major depressive disorder, posttraumatic stress disorder, or bipolar disorder to date. Critical discussion of discrepant findings and broad strengths and weaknesses of the current body of literature is provided. Recommended future directions for the field of molecular imaging to further elucidate the neurobiological substrates of chronic stress-related disorders are also discussed. This article is part of the inaugural issue for the journal focused on various aspects of chronic stress. PMID:29862379

Chronic traumatic stress impairs memory in mice: Potential roles of acetylcholine, neuroinflammation and corticotropin releasing factor expression in the hippocampus.

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Bhakta, Ami; Gavini, Kartheek; Yang, Euitaek; Lyman-Henley, Lani; Parameshwaran, Kodeeswaran

2017-09-29

Chronic stress in humans can result in multiple adverse psychiatric and neurobiological outcomes, including memory deficits. These adverse outcomes can be more severe if each episode of stress is very traumatic. When compared to acute or short term stress relatively little is known about the effects of chronic traumatic stress on memory and molecular changes in hippocampus, a brain area involved in memory processing. Here we studied the effects of chronic traumatic stress in mice by exposing them to adult Long Evan rats for 28 consecutive days and subsequently analyzing behavioral outcomes and the changes in the hippocampus. Results show that stressed mice developed memory deficits when assayed with radial arm maze tasks. However, chronic traumatic stress did not induce anxiety, locomotor hyperactivity or anhedonia. In the hippocampus of stressed mice interleukin-1β protein expression was increased along with decreased corticotropin releasing hormone (CRH) gene expression. Furthermore, there was a reduction in acetylcholine levels in the hippocampus of stressed mice. There were no changes in brain derived neurotrophic factor (BDNF) or nerve growth factor (NGF) levels in the hippocampus of stressed mice. Gene expression of immediate early genes (Zif268, Arc, C-Fos) as well as glucocorticoid and mineralocorticoid receptors were also not affected by chronic stress. These data demonstrate that chronic traumatic stress followed by a recovery period might lead to development of resilience resulting in the development of selected, most vulnerable behavioral alterations and molecular changes in the hippocampus. Copyright © 2017 Elsevier B.V. All rights reserved.

Estrogen-dependent effects on behavior, lipid-profile, and glycemic index of ovariectomized rats subjected to chronic restraint stress.

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da Silva, Caroline Calice; Lazzaretti, Camilla; Fontanive, Tiago; Dartora, Daniela Ravizzoni; Bauereis, Brian; Gamaro, Giovana Duzzo

2014-03-01

Stress has been shown to negatively affect the immune system, alter the body's metabolism, and play a strong role in the development of mood disorders. These effects are mainly driven through the release of hormones from the hypothalamic-pituitary-adrenal axis (HPA). Additionally, women are more likely to be affected by stress due to the estrogen fluctuation associated with their menstrual cycle. This study aims to evaluate the effect of chronic restraint stress, applied for 30 days, and estrogen replacement on behavior, glucose level, and the lipid profile of ovariectomized rats. Our results suggest that stress increases sweet food consumption in OVX females treated with estradiol (E2), but reduces consumption in animals not treated. Furthermore, stress increases locomotor activity and anxiety as assessed by the Open Field test and in the Elevated Plus Maze. Similarly, our results suggest that E2 increases anxiety in female rats under the same behavioral tests. In addition, stress reduces glucose and TC levels. Moreover, stress increase TG levels in the presence of E2 and decrease in its absence, as well as the estradiol increase TG levels in stressed groups and reduced in non-stressed groups. Our data suggest an important interaction between stress and estrogen, showing that hormonal status can induce changes in the animal's response to stress. Copyright © 2014 Elsevier B.V. All rights reserved.

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

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Zhang Tianzhu

2014-01-01

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

Signs of chronic stress in women with recurrent candida vulvovaginitis.

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Ehrström, Sophia M; Kornfeld, Dan; Thuresson, Jessica; Rylander, Eva

2005-10-01

The purpose of this study was to determine whether there is an association between recurrent vulvovaginal candida and chronic stress. Chronic stress affects the hypothalamus-pituitary-adrenal axis, which influences the immune function. Recurrent candida vulvovaginitis is increasing. Women with recurrent vulvovaginal candida (n = 35) and age-matched healthy control subjects (n = 35) collected saliva for the analysis of cortisol. Hormone analyses of blood samples and vulvovaginal examinations were performed. A questionnaire was completed. Morning rise cortisol level was significantly blunted among patients compared with control subjects (P vulvovaginal candida, compared with control subjects. More patients than control subjects reported a history of condyloma, bacterial vaginosis, and herpes genitalis. No differences were seen between patients and control subjects regarding sexual hormone binding globulin, dihydroepiandrosterone, testosterone or Hemoglobin A1c. Morning rise salivary cortisol level is blunted in women with recurrent vulvovaginal candida, which indicates signs of chronic stress. The higher incidence of vulvovaginal infections in these women compared with control subjects may reflect impaired immunity, which may be due to chronic stress.

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.

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

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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

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

International Nuclear Information System (INIS)

Rodrigues, S.; Antunes, S.C.; Correia, A.T.; Nunes, B.

2016-01-01

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

[The role of stress-induced chronic subclinical inflammation in the pathogenesis of the chronic pelvic pain syndrome IIIB in men].

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Shormanov, I S; Mozhaev, I I; Sokolova, Kh A; Solovev, A S

2017-12-01

This literature review of recent clinical and experimental studies describes the role of oxidative stress in the multifactorial and interdisciplinary pathogenesis of non-inflammatory chronic pelvic pain syndrome IIIB (CPPS-IIIB) in men. The authors outline general biological nature of oxidative stress and its mechanisms. More detailed information is presented on cytokine-mediated chronic subclinical inflammation, one of the key mechanisms of oxidative stress, which is currently being actively studied. It is shown that the imbalance between pro- and anti-inflammatory cytokines observed in patients with CPPS-IIIB can explain some features of the clinical course (in particular, the characteristics of the pain syndrome) and the progression of this disease. In this regard, cytokine profiling of prostatic secretion can provide valuable diagnostic, prognostic and monitoring information in the management of this category of patients. Recently published evidence has demonstrated the essential role of the cytokine-mediated chronic inflammatory response as a mechanism of oxidative stress in the pathogenesis of CPPS-IIIB. Further studies in this area are warranted and in the long term may become a basis for the development of new effective pathogenetic pharmacotherapy of CPPS-IIIB.

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

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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.

Interplay between cytoskeletal stresses and cell adaptation under chronic flow.

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Deepika Verma

Full Text Available Using stress sensitive FRET sensors we have measured cytoskeletal stresses in α-actinin and the associated reorganization of the actin cytoskeleton in cells subjected to chronic shear stress. We show that long-term shear stress reduces the average actinin stress and this effect is reversible with removal of flow. The flow-induced changes in cytoskeletal stresses are found to be dynamic, involving a transient decrease in stress (phase-I, a short-term increase (3-6 min (Phase-II, followed by a longer-term decrease that reaches a minimum in ~20 min (Phase-III, before saturating. These changes are accompanied by reorganization of the actin cytoskeleton from parallel F-actin bundles to peripheral bundles. Blocking mechanosensitive ion channels (MSCs with Gd(3+ and GsMTx4 (a specific inhibitor eliminated the changes in cytoskeletal stress and the corresponding actin reorganization, indicating that Ca(2+ permeable MSCs participate in the signaling cascades. This study shows that shear stress induced cell adaptation is mediated via MSCs.

Obesity and chronic stress are able to desynchronize the temporal pattern of serum levels of leptin and triglycerides.

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de Oliveira, Carla; Scarabelot, Vanessa Leal; de Souza, Andressa; de Oliveira, Cleverson Moraes; Medeiros, Liciane Fernandes; de Macedo, Isabel Cristina; Marques Filho, Paulo Ricardo; Cioato, Stefania Giotti; Caumo, Wolnei; Torres, Iraci L S

2014-01-01

Disruption of the circadian system can lead to metabolic dysfunction as a response to environmental alterations. This study assessed the effects of the association between obesity and chronic stress on the temporal pattern of serum levels of adipogenic markers and corticosterone in rats. We evaluated weekly weight, delta weight, Lee index, and weight fractions of adipose tissue (mesenteric, MAT; subcutaneous, SAT; and pericardial, PAT) to control for hypercaloric diet-induced obesity model efficacy. Wistar rats were divided into four groups: standard chow (C), hypercaloric diet (HD), stress plus standard chow (S), and stress plus hypercaloric diet (SHD), and analyzed at three time points: ZT0, ZT12, and ZT18. Stressed animals were subjected to chronic stress for 1h per day, 5 days per week, during 80 days. The chronic exposure to a hypercaloric diet was an effective model for the induction of obesity and metabolic syndrome, increasing delta weight, Lee index, weight fractions of adipose tissue, and triglycerides and leptin levels. We confirmed the presence of a temporal pattern in the release of triglycerides, corticosterone, leptin, and adiponectin in naïve animals. Chronic stress reduced delta weight, MAT weight, and levels of triglycerides, total cholesterol, and leptin. There were interactions between chronic stress and obesity and serum total cholesterol levels, between time points and obesity and adiponectin and corticosterone levels, and between time points and chronic stress and serum leptin levels. In conclusion, both parameters were able to desynchronize the temporal pattern of leptin and triglyceride release, which could contribute to the development of metabolic diseases such as obesity and metabolic syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

Effects of Psychosocial Stress on Subsequent Hemorrhagic Shock and Resuscitation in Male Mice.

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Langgartner, Dominik; Wachter, Ulrich; Hartmann, Clair; Gröger, Michael; Vogt, Josef; Merz, Tamara; McCook, Oscar; Fink, Marina; Kress, Sandra; Georgieff, Michael; Kunze, Julia F; Radermacher, Peter L; Reber, Stefan O; Wepler, Martin

2018-06-08

Hypoxemia and tissue ischemia during hemorrhage as well as formation of oxygen and nitrogen radicals during resuscitation promote hyperinflammation and, consequently, trigger severe multiple-organ-failure (MOF). Individuals diagnosed with stress-related disorders or reporting a life history of psychosocial stress are characterized by chronic low-grade inflammation and a reduced glucocorticoid (GC) signaling. We hypothesized that exposure to chronic psychosocial stress during adulthood prior to hemorrhagic shock increases oxidative/nitrosative stress and therefore the risk of developing MOF in mice. To induce chronic psychosocial stress linked to mild immune activation and reduced GC signaling in male mice, the chronic subordinate colony housing (CSC) paradigm was employed. Single-housed (SHC) mice were used as controls. Subsequently, CSC and SHC mice were exposed to hemorrhagic shock following resuscitation to investigate the effects of prior psychosocial stress load on survival, organ function, metabolism, oxidative/nitrosative stress, and inflammatory readouts. An increased adrenal weight in CSC mice indicates that the stress paradigm reliably worked. However, no effect of prior psychosocial stress on outcome after subsequent hemorrhage and resuscitation could be detected. Chronic psychosocial stress during adulthood is not sufficient to promote hemodynamic complications, organ dysfunction, metabolic disturbances and did not increase the risk of MOF after subsequent hemorrhage and resuscitation. Intravenous norepinephrine to keep target hemodynamics might have led to a certain level of oxidative stress in both groups and, therefore, disguised potential effects of chronic psychosocial stress on organ function after hemorrhagic shock in the present murine trauma model.

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

. 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......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...

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

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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...

Short-term exposure to enriched environment rescues chronic stress-induced impaired hippocampal synaptic plasticity, anxiety, and memory deficits.

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Bhagya, Venkanna Rao; Srikumar, Bettadapura N; Veena, Jayagopalan; Shankaranarayana Rao, Byrathnahalli S

2017-08-01

Exposure to prolonged stress results in structural and functional alterations in the hippocampus including reduced long-term potentiation (LTP), neurogenesis, spatial learning and working memory impairments, and enhanced anxiety-like behavior. On the other hand, enriched environment (EE) has beneficial effects on hippocampal structure and function, such as improved memory, increased hippocampal neurogenesis, and progressive synaptic plasticity. It is unclear whether exposure to short-term EE for 10 days can overcome restraint stress-induced cognitive deficits and impaired hippocampal plasticity. Consequently, the present study explored the beneficial effects of short-term EE on chronic stress-induced impaired LTP, working memory, and anxiety-like behavior. Male Wistar rats were subjected to chronic restraint stress (6 hr/day) over a period of 21 days, and then they were exposed to EE (6 hr/day) for 10 days. Restraint stress reduced hippocampal CA1-LTP, increased anxiety-like symptoms in elevated plus maze, and impaired working memory in T-maze task. Remarkably, EE facilitated hippocampal LTP, improved working memory performance, and completely overcame the effect of chronic stress on anxiety behavior. In conclusion, exposure to EE can bring out positive effects on synaptic plasticity in the hippocampus and thereby elicit its beneficial effects on cognitive functions. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Chronic restraint stress during withdrawal increases vulnerability to drug priming-induced cocaine seeking via a dopamine D1-like receptor-mediated mechanism.

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Ball, Kevin T; Stone, Eric; Best, Olivia; Collins, Tyler; Edson, Hunter; Hagan, Erin; Nardini, Salvatore; Neuciler, Phelan; Smolinsky, Michael; Tosh, Lindsay; Woodlen, Kristin

2018-06-01

A major obstacle in the treatment of individuals with cocaine addiction is their high propensity for relapse. Although the clinical scenario of acute stress-induced relapse has been well studied in animal models, few pre-clinical studies have investigated the role of chronic stress in relapse or the interaction between chronic stress and other relapse triggers. We tested the effect of chronic restraint stress on cocaine seeking in rats using both extinction- and abstinence-based animal relapse models. Rats were trained to press a lever for I.V. cocaine infusions (0.50 mg/kg/infusion) paired with a discrete tone + light cue in daily 3-h sessions. Following self-administration, rats were exposed to a chronic restraint stress procedure (3 h/day) or control procedure (unstressed) during the first seven days of a 13-day extinction period during which lever presses had no programmed consequences. This was followed by cue- and cocaine priming-induced drug seeking tests. In a separate group of rats, cocaine seeking was assessed during forced abstinence both before and after the same chronic stress procedure. A history of chronic restraint stress was associated with increased cocaine priming-induced drug seeking, an effect attenuated by co-administration of SCH-23390 (10.0 μg/kg; i.p.), a dopamine D 1 -like receptor antagonist, with daily restraint. Repeated SCH-23390 administration but not stress during extinction increased cue-induced reinstatement. Exposure to chronic stress during early withdrawal may confer lasting vulnerability to some types of relapse, and dopamine D 1 -like receptors appear to mediate both chronic stress effects on cocaine seeking and extinction of cocaine seeking. Copyright © 2018 Elsevier B.V. All rights reserved.

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains.

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van Boxelaere, Michiel; Clements, Jason; Callaerts, Patrick; D'Hooge, Rudi; Callaerts-Vegh, Zsuzsanna

2017-01-01

Alterations in the social and cognitive domain are considered important indicators for increased disability in many stress-related disorders. Similar impairments have been observed in rodents chronically exposed to stress, mimicking potential endophenotypes of stress-related psychopathologies such as major depression disorder (MDD), anxiety, conduct disorder, and posttraumatic stress disorder (PTSD). Data from numerous studies suggest that deficient plasticity mechanisms in hippocampus (HC) and prefrontal cortex (PFC) might underlie these social and cognitive deficits. Specifically, stress-induced deficiencies in neural plasticity have been associated with a hypodopaminergic state and reduced neural plasticity persistence. Here we assessed the effects of unpredictable chronic mild stress (UCMS) on exploratory, social and cognitive behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J) that differ in their dopaminergic profile. Exposure to chronic stress resulted in impaired circadian rhythmicity, sociability and social cognition in both inbred strains, but differentially affected activity patterns and contextual discrimination performance. These stress-induced behavioral impairments were accompanied by reduced expression levels of brain derived neurotrophic factor (BDNF) in the prefrontal cortex. The strain-specific cognitive impairment was coexistent with enhanced plasma corticosterone levels and reduced expression of genes related to dopamine signaling in hippocampus. These results underline the importance of assessing different strains with multiple test batteries to elucidate the neural and genetic basis of social and cognitive impairments related to chronic stress.

The brain-derived neurotrophic factor pathway, life stress, and chronic multi-site musculoskeletal pain.

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Generaal, Ellen; Milaneschi, Yuri; Jansen, Rick; Elzinga, Bernet M; Dekker, Joost; Penninx, Brenda W J H

2016-01-01

Brain-derived neurotrophic factor (BDNF) disturbances and life stress, both independently and in interaction, have been hypothesized to induce chronic pain. We examined whether (a) the BDNF pathway (val(66)met genotype, gene expression, and serum levels), (b) early and recent life stress, and (c) their interaction are associated with the presence and severity of chronic multi-site musculoskeletal pain. Cross-sectional data are from 1646 subjects of the Netherlands Study of Depression and Anxiety. The presence and severity of chronic multi-site musculoskeletal pain were determined using the Chronic Pain Grade (CPG) questionnaire. The BDNF val(66)met polymorphism, BDNF gene expression, and BDNF serum levels were measured. Early life stress before the age of 16 was assessed by calculating a childhood trauma index using the Childhood Trauma Interview. Recent life stress was assessed as the number of recent adverse life events using the List of Threatening Events Questionnaire. Compared to val(66)val, BDNF met carriers more often had chronic pain, whereas no differences were found for BDNF gene expression and serum levels. Higher levels of early and recent stress were both associated with the presence and severity of chronic pain (p stress in the associations with chronic pain presence and severity. This study suggests that the BDNF gene marks vulnerability for chronic pain. Although life stress did not alter the impact of BDNF on chronic pain, it seems an independent factor in the onset and persistence of chronic pain. © The Author(s) 2016.

Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response.

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Kodavanti, Urmila P

2016-12-01

Inhaled pollutants produce effects in virtually all organ systems in our body and have been linked to chronic diseases including hypertension, atherosclerosis, Alzheimer's and diabetes. A neurohormonal stress response (referred to here as a systemic response produced by activation of the sympathetic nervous system and hypothalamus-pituitary-adrenal (HPA)-axis) has been implicated in a variety of psychological and physical stresses, which involves immune and metabolic homeostatic mechanisms affecting all organs in the body. In this review, we provide new evidence for the involvement of this well-characterized neurohormonal stress response in mediating systemic and pulmonary effects of a prototypic air pollutant - ozone. A plethora of systemic metabolic and immune effects are induced in animals exposed to inhaled pollutants, which could result from increased circulating stress hormones. The release of adrenal-derived stress hormones in response to ozone exposure not only mediates systemic immune and metabolic responses, but by doing so, also modulates pulmonary injury and inflammation. With recurring pollutant exposures, these effects can contribute to multi-organ chronic conditions associated with air pollution. This review will cover, 1) the potential mechanisms by which air pollutants can initiate the relay of signals from respiratory tract to brain through trigeminal and vagus nerves, and activate stress responsive regions including hypothalamus; and 2) the contribution of sympathetic and HPA-axis activation in mediating systemic homeostatic metabolic and immune effects of ozone in various organs. The potential contribution of chronic environmental stress in cardiovascular, neurological, reproductive and metabolic diseases, and the knowledge gaps are also discussed. This article is part of a Special Issue entitled Air Pollution, edited by Wenjun Ding, Andrew J. Ghio and Weidong Wu. Published by Elsevier B.V.

Erythropoietin prevents the effect of chronic restraint stress on the number of hippocampal CA3c dendritic terminals-relation to expression of genes involved in synaptic plasticity, angiogenesis, inflammation, and oxidative stress in male rats

DEFF Research Database (Denmark)

Aalling, Nadia; Hageman, Ida; Miskowiak, Kamilla Woznica

2018-01-01

. Interestingly, these effects seemed to be mechanistically distinct, as stress and EPO had differential effects on gene expression. While chronic restraint stress lowered the expression of spinophilin, tumor necrosis factor α, and heat shock protein 72, EPO increased expression of hypoxia-inducible factor-2α...... and lowered the expression of vascular endothelial growth factor in hippocampus. These findings indicate that the effects of treatment with EPO follow different molecular pathways and do not directly counteract the effects of stress in the hippocampus....

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

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Ionan Marigómez

Full Text Available 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.

Oxidative and Anti-Oxidative Stress Markers in Chronic Glaucoma: A Systematic Review and Meta-Analysis

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Benoist d’Azy, Cédric; Pereira, Bruno; Chiambaretta, Frédéric

2016-01-01

Chronic glaucoma is a multifactorial disease among which oxidative stress may play a major pathophysiological role. We conducted a systematic review and meta-analysis to evaluate the levels of oxidative and antioxidative stress markers in chronic glaucoma compared with a control group. The PubMed, Cochrane Library, Embase and Science Direct databases were searched for studies reporting oxidative and antioxidative stress markers in chronic glaucoma and in healthy controls using the following keywords: “oxidative stress” or “oxidant stress” or “nitrative stress” or “oxidative damage” or “nitrative damage” or “antioxidative stress” or “antioxidant stress” or “antinitrative stress” and “glaucoma”. We stratified our meta-analysis on the type of biomarkers, the type of glaucoma, and the origin of the sample (serum or aqueous humor). We included 22 case-control studies with a total of 2913 patients: 1614 with glaucoma and 1319 healthy controls. We included 12 studies in the meta-analysis on oxidative stress markers and 19 on antioxidative stress markers. We demonstrated an overall increase in oxidative stress markers in glaucoma (effect size = 1.64; 95%CI 1.20–2.09), ranging from an effect size of 1.29 in serum (95%CI 0.84–1.74) to 2.62 in aqueous humor (95%CI 1.60–3.65). Despite a decrease in antioxidative stress marker in serum (effect size = –0.41; 95%CI –0.72 to –0.11), some increased in aqueous humor (superoxide dismutase, effect size = 3.53; 95%CI 1.20–5.85 and glutathione peroxidase, effect size = 6.60; 95%CI 3.88–9.31). The differences in the serum levels of oxidative stress markers between glaucoma patients and controls were significantly higher in primary open angle glaucoma vs primary angle closed glaucoma (effect size = 12.7; 95%CI 8.78–16.6, P stress increased in glaucoma, both in serum and aqueous humor. Malonyldialdehyde seemed the best biomarkers of oxidative stress in serum. The increase of some

Moderators and Mediators of the Relationship Between Stress and Insomnia: Stressor Chronicity, Cognitive Intrusion, and Coping

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Pillai, Vivek; Roth, Thomas; Mullins, Heather M.; Drake, Christopher L.

2014-01-01

Study Objectives: To assess moderators, such as stressor chronicity, and mediators, including stress response in the form of cognitive intrusion and coping behavior, of the prospective association between naturalistic stress and incident insomnia. Design: Longitudinal. Setting: Epidemiological. Participants: A community-based sample of good sleepers (n = 2,892) with no lifetime history of insomnia. Interventions: None. Measurements and Results: Participants reported the number of stressful events they had encountered at baseline, as well as the perceived severity and chronicity of each event. Similarly, volitional stress responses such as coping, as well as more involuntary responses such as cognitive intrusion were assayed for each stressor. Follow-up assessment 1 y hence revealed an insomnia incidence rate of 9.1%. Stress exposure was a significant predictor of insomnia onset, such that the odds of developing insomnia increased by 19% for every additional stressor. Chronicity significantly moderated this relationship, such that the likelihood of developing insomnia as a result of stress exposure increased as a function of chronicity. Cognitive intrusion significantly mediated the association between stress exposure and insomnia. Finally, three specific coping behaviors also acted as mediators: behavioral disengagement, distraction, and substance use. Conclusions: Most studies characterize the relationship between stress exposure and insomnia as a simple dose-response phenomenon. However, our data suggest that certain stressor characteristics significantly moderate this association. Stress response in the form of cognitive intrusion and specific maladaptive coping behaviors mediate the effects of stress exposure. These findings highlight the need for a multidimensional approach to stress assessment in future research and clinical practice. Citation: Pillai V, Roth T, Mullins HM, Drake CL. Moderators and mediators of the relationship between stress and insomnia

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

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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.

Chronic restraint stress impairs endocannabinoid mediated suppression of GABAergic signaling in the hippocampus of adult male rats.

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Hu, Wen; Zhang, Mingyue; Czéh, Boldizsár; Zhang, Weiqi; Flügge, Gabriele

2011-07-15

Chronic stress, a risk factor for the development of psychiatric disorders, is known to induce alterations in neuronal networks in many brain areas. Previous studies have shown that chronic stress changes the expression of the cannabinoid receptor 1 (CB1) in the brains of adult rats, but neurophysiological consequences of these changes remained unclear. Here we demonstrate that chronic restraint stress causes a dysfunction in CB1 mediated modulation of GABAergic transmission in the hippocampus. Using an established protocol, adult male Sprague Dawley rats were daily restrained for 21 days and whole-cell voltage clamp was performed at CA1 pyramidal neurons. When recording carbachol-evoked inhibitory postsynaptic currents (IPSCs) which presumably originate from CB1 expressing cholecystokinin (CCK) interneurons, we found that depolarization-induced suppression of inhibition (DSI) was impaired by the stress. DSI is a form of short-term plasticity at GABAergic synapses that is known to be CB1 mediated and has been suggested to be involved in hippocampal information encoding. Chronic stress attenuated the depolarization-induced suppression of the frequency of carbachol-evoked IPSCs. Incubation with a CB1 receptor antagonist prevented this DSI effect in control but not in chronically stressed animals. The stress-induced impairment of CB1-mediated short-term plasticity at GABAergic synapses may underlie cognitive deficits which are commonly observed in animal models of stress as well as in patients with stress-related psychiatric disorders. Copyright © 2011 Elsevier Inc. All rights reserved.

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

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Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. 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 subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

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

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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…

The Role of Chronic Psychosocial Stress in Explaining Racial Differences in Stress Reactivity and Pain Sensitivity.

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Gordon, Jennifer L; Johnson, Jacqueline; Nau, Samantha; Mechlin, Beth; Girdler, Susan S

To examine the role of psychosocial factors in mediating the relationship between African American (AA) race and both increased pain sensitivity and blunted stress reactivity. Participants included 133 AA and non-Hispanic white (nHW) individuals (mean [SD] age, 37 [9]) matched for age, sex, and socioeconomic status. Participants underwent mental stress testing (Trier Social Stress Test) while cardiovascular, hemodynamic, and neuroendocrine reactivity were measured. Participants completed questionnaires assessing potential sources of psychosocial stress and were tested for pain responses to cold pain and the temporal summation of heat pulses. Mediation analyses were used to determine the extent to which exposure to psychosocial stress accounted for the observed racial differences in stress reactivity and pain. Chronic stress exposure and reactivity to mental stress was largely similar among AAs and nHWs; however, AAs exhibited heightened pain to both cold (p = .012) and heat (p = .004). Racial differences in the relationship between stress reactivity and pain were also observed: while greater stress reactivity was associated with decreased pain among nHWs, reactivity was either unrelated to or even positively associated with pain among AAs (e.g., r = -.21 among nHWs and r = .41 among AAs for stroke volume reactivity and cold pressor intensity). Adjusting for minor racial differences in chronic psychosocial stress did not change these findings. Accounting for psychosocial factors eliminated racial differences in stress reactivity but not racial differences in sensitivity to experimental pain tasks. Increased exposure to chronic stress may not explain AAs' increased pain sensitivity in laboratory settings.

Sweet food improves chronic stress-induced irritable bowel syndrome-like symptoms in rats.

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Rho, Sang-Gyun; Kim, Yong Sung; Choi, Suck Chei; Lee, Moon Young

2014-03-07

To investigate whether palatable sweet foods have a beneficial effect on chronic stress-induced colonic motility and inflammatory cytokines. Adult male rats were divided into 3 groups: control (CON, n = 5), chronic variable stress with chow (CVS-A, n = 6), and chronic variable stress with chow and sweet food (CVS-B, n = 6). The rats were fed standard rodent chow as the chow food and/or AIN-76A as the sweet food. A food preference test for AIN-76A was performed in another group of normal rats (n = 10) for twelve days. Fecal pellet output (FPO) was measured for 6 wk during water bedding stress in the CVS groups. The weight of the adrenal glands, adrenocorticotropic hormone (ACTH) and corticosterone levels in plasma were measured. The expression levels of transforming growth factor-β, interleukin (IL)-2, and interferon-gamma (IFN-γ) were measured in the distal part of colonic tissues and plasma using Western blot analysis. In sweet preference test, all rats initially preferred sweet food to chow food. However, the consumption rate of sweet food gradually decreased and reduced to below 50% of total intake eight days after sweet food feeding. Accumulated FPO was higher in the CVS-A group compared with the CVS-B group over time. All stress groups showed significant increases in the adrenal to body weight ratio (CVS-A, 0.14 ± 0.01; CVS-B, 0.14 ± 0.01) compared with the control group (0.12 ± 0.01, P food ingestion during CVS might have an effect on the reduction of stress-induced colonic hyper-motility and pro-inflammatory cytokine production in rats.

Effects of chronic social stress and maternal intranasal oxytocin and vasopressin on offspring interferon γ and behavior

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Chris Anthony Murgatroyd

2016-12-01

Full Text Available Recent studies support the hypothesis that the adverse effects of early life adversity and transgenerational stress on neural plasticity and behavior are mediated by inflammation. The objective of the present study was to investigate the immune and behavioural programming effects of intranasal (IN vasopressin (AVP and oxytocin (OXT treatment of chronic social stress (CSS exposed F1 dams on F2 juvenile female offspring. It was hypothesized that maternal AVP and OXT treatment would have preventative effects on social stress induced deficits in offspring anxiety and social behavior, and that these effects would be associated with changes in interferon γ (IFNγ. Control and CSS exposed F1 dams were administered IN saline, AVP, or OXT during lactation and the F2 juvenile female offspring were assessed for basal plasma IFNγ and perseverative, anxiety, and social behavior. CSS F2 female juvenile offspring had elevated IFNγ levels and exhibited increased repetitive/perseverative and anxiety behaviours and deficits in social behavior. These effects were modulated by AVP and OXT in a context and behavior dependent manner, with OXT exhibiting preventative effects on repetitive and anxiety behaviours and AVP possessing preventative effects on social behavior deficits and anxiety. Basal IFNγ levels were elevated in the F2 offspring of OXT treated F1 dams, but IFNγ was not correlated with the behavioural effects. These results support the hypothesis that maternal AVP and OXT treatment have context and behavior specific effects on peripheral IFNγ levels and perseverative, anxiety, and social behaviours in the female offspring of early life social stress exposed dams. Both maternal AVP and OXT are effective at preventing social stress induced increases in self-directed measures of anxiety, and AVP is particularly effective at preventing impairments in overall social contact. Oxytocin is specifically effective at preventing repetitive

Protective effect of low dose caffeine on psychological stress and cognitive function.

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Çakır, Özgür Kasımay; Ellek, Nurfitnat; Salehin, Nabila; Hamamcı, Rabia; Keleş, Hülya; Kayalı, Damla Gökçeoğlu; Akakın, Dilek; Yüksel, Meral; Özbeyli, Dilek

2017-01-01

Caffeine is an adrenergic antagonist that enhances neuronal activity. Psychological stress depresses cognitive function. To investigate the effects of acute and chronic low dose caffeine on anxiety-like behavior and cognitive functions of acute or chronic psychological stressed rats. Acute or chronic caffeine (3mg/kg) was administered to male Sprague Dawley rats (200-250g, n=42) before acute (cat odor) and chronic variable psychological stress (restraint overcrowding stress, elevated plus maze, cat odor, forced swimming) induction. Anxiety and cognitive functions were evaluated by hole-board and object recognition tests. The brain glutathione and malondialdehyde assays, myeloperoxidase, nitric oxide (NO), superoxide dismutase (SOD), luminol and lucigenin activity and histological examination were done. ANOVA and Student's t-test were used for statistical analysis. The depressed cognitive function with chronic stress exposure and the increased anxiety-like behavior with both stress inductions were improved via both caffeine applications (pcaffeine pretreatments in chronic stressed rats, and chronic caffeine in acute stressed ones reduced the elevated myeloperoxidase activities (pcaffeine (pcaffeine (pcaffeine decreased SOD activity (pcaffeine. The increased anxiety-like behavior and depleted cognitive functions under stress conditions were improved with both acute and predominantly chronic caffeine pretreatments by decreasing oxidative damage parameters. Copyright © 2016 Elsevier Inc. All rights reserved.

Strategies for Coping with Stress and Chronic Pain.

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Meyer, Genevieve Rogge

This guide presents strategies used in Pain Management and Stress Reduction workshops for helping the elderly cope with stress and chronic pain. Client evaluations of the workshops are given along with an analysis of the clients' presenting problems. Coping strategies described include: the relaxation response, imagery, daily logs, journal…

Educators' emotion regulation strategies and their physiological indicators of chronic stress over 1 year.

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Katz, Deirdre A; Harris, Alexis; Abenavoli, Rachel; Greenberg, Mark T; Jennings, Patricia A

2018-04-01

Studies show teaching is a highly stressful profession and that chronic work stress is associated with adverse health outcomes. This study analysed physiological markers of stress and self-reported emotion regulation strategies in a group of middle school teachers over 1 year. Chronic physiological stress was assessed with diurnal cortisol measures at three time points over 1 year (fall, spring, fall). The aim of this longitudinal study was to investigate the changes in educators' physiological level of stress. Results indicate that compared to those in the fall, cortisol awakening responses were blunted in the spring. Further, this effect was ameliorated by the summer break. Additionally, self-reported use of the emotion regulation strategy reappraisal buffered the observed blunting that occurred in the spring. Copyright © 2017 John Wiley & Sons, Ltd.

Chronic restraint-induced stress has little modifying effect on radiation hematopoietic toxicity in mice

International Nuclear Information System (INIS)

Wang, Bing; Tanaka, Kaoru; Katsube, Takanori; Ninomiya, Yasuharu; Vares, Guillaume; Nakajima, Tetsuo; Nenoi, Mitsuru; Liu Qiang; Morita, Akinori

2015-01-01

Both radiation and stresses cause detrimental effects on humans. Besides possible health effects resulting directly from radiation exposure, the nuclear plant accident is a cause of social psychological stresses. A recent study showed that chronic restraint-induced stresses (CRIS) attenuated Trp53 functions and increased carcinogenesis susceptibility of Trp53-heterozygous mice to total-body X-irradiation (TBXI), having a big impact on the academic world and a sensational effect on the public, especially the residents living in radioactively contaminated areas. It is important to investigate the possible modification effects from CRIS on radiation-induced health consequences in Trp53 wild-type (Trp53wt) animals. Prior to a carcinogenesis study, effects of TBXI on the hematopoietic system under CRIS were investigated in terms of hematological abnormality in the peripheral blood and residual damage in the bone marrow erythrocytes using a mouse restraint model. Five-week-old male Trp53wt C57BL/6J mice were restrained 6 h per day for 28 consecutive days, and TBXI (4 Gy) was given on the 8th day. Results showed that CRIS alone induced a marked decrease in the red blood cell (RBC) and the white blood cell (WBC) count, while TBXI caused significantly lower counts of RBCs, WBCs and blood platelets, and a lower concentration of hemoglobin regardless of CRIS. CRIS alone did not show any significant effect on erythrocyte proliferation and on induction of micronucleated erythrocytes, whereas TBXI markedly inhibited erythrocyte proliferation and induced a significant increase in the incidences of micronucleated erythrocytes, regardless of CRIS. These findings suggest that CRIS does not have a significant impact on radiation-induced detrimental effects on the hematopoietic system in Trp53wt mice. (author)

Posttraumatic stress disorder symptoms in youth with vs without chronic pain.

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Noel, Melanie; Wilson, Anna C; Holley, Amy Lewandowski; Durkin, Lindsay; Patton, Michaela; Palermo, Tonya M

2016-10-01

Chronic pain and posttraumatic stress disorder (PTSD) symptoms have been found to co-occur in adults; however, research has not examined this co-occurrence in adolescence, when pediatric chronic pain often first emerges. The aims of this study were to compare the frequency and intensity of PTSD symptoms and stressful life events in cohorts of youth with (n = 95) and without (n = 100) chronic pain and their parents and to determine the association between PTSD symptoms, health-related quality of life, and pain symptoms within the chronic pain sample. All participants completed questionnaire measures through an online survey. Findings revealed that youth with chronic pain and their parents had significantly higher levels of PTSD symptoms as compared with pain-free peers. More youth with chronic pain (32%) and their parents (20%) reported clinically significant elevations in PTSD symptoms than youth without chronic pain (8%) and their parents (1%). Youth with chronic pain also reported a greater number of stressful life events than those without chronic pain, and this was associated with higher PTSD symptoms. Among the chronic pain cohort, higher levels of PTSD symptoms were predictive of worse health-related quality of life and were associated with higher pain intensity, unpleasantness, and interference. Results suggest that elevated PTSD symptoms are common and linked to reduced functioning among youth with chronic pain. Future research is needed to examine PTSD at the diagnostic level and the underlying mechanisms that may explain why this co-occurrence exists.

Beneficial Effect of Fluoxetine and Sertraline on Chronic Stress-Induced Tumor Growth and Cell Dissemination in a Mouse Model of Lymphoma: Crucial Role of Antitumor Immunity

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María Emilia Di Rosso

2018-06-01

Full Text Available Clinical data and experimental studies have suggested a relationship between psychosocial factors and cancer prognosis. Both, stress effects on the immune system and on tumor biology were analyzed independently. However, there are few studies regarding the stress influence on the interplay between the immune system and tumor biology. Moreover, antidepressants have been used in patients with cancer to alleviate mood disorders. Nevertheless, there is contradictory evidence about their action on cancer prognosis. In this context, we investigated the effect of chronic stress on tumor progression taking into account both its influence on the immune system and on tumor biology. Furthermore, we analyzed the action of selective serotonin reuptake inhibitors, fluoxetine and sertraline, in these effects. For this purpose, C57BL/6J mice submitted or not to a chronic stress model and treated or not with fluoxetine or sertraline were subcutaneously inoculated with EL4 cells to develop solid tumors. Our results indicated that chronic stress leads to an increase in both tumor growth and tumor cell dissemination. The analysis of cell cycle regulatory proteins showed that stress induced an increase in the mRNA levels of cyclins A2, D1, and D3 and a decrease in mRNA levels of cell cycle inhibitors p15, p16, p21, p27, stimulating cell cycle progression. Moreover, an augment of mRNA levels of metalloproteases (MMP-2 and MMP-9, a decrease of inhibitors of metalloproteases mRNA levels (TIMP 1, 2, and 3, and an increase in migration ability were found in tumors from stressed animals. In addition, a significant decrease of antitumor immune response in animals under stress was found. Adoptive lymphoid cell transfer experiments indicated that the reduced immune response in stressed animals influenced both the tumor growth and the metastatic capacity of tumor cells. Finally, we found an important beneficious effect of fluoxetine or sertraline treatment on cancer

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

International Nuclear Information System (INIS)

Davidson, L.M.; Fleming, R.; Baum, A.

1987-01-01

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

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

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Davidson, L M; Fleming, R; Baum, A

1987-01-01

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

Unpredictable chronic mild stress differentially impairs social and contextual discrimination learning in two inbred mouse strains.

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Michiel van Boxelaere

Full Text Available Alterations in the social and cognitive domain are considered important indicators for increased disability in many stress-related disorders. Similar impairments have been observed in rodents chronically exposed to stress, mimicking potential endophenotypes of stress-related psychopathologies such as major depression disorder (MDD, anxiety, conduct disorder, and posttraumatic stress disorder (PTSD. Data from numerous studies suggest that deficient plasticity mechanisms in hippocampus (HC and prefrontal cortex (PFC might underlie these social and cognitive deficits. Specifically, stress-induced deficiencies in neural plasticity have been associated with a hypodopaminergic state and reduced neural plasticity persistence. Here we assessed the effects of unpredictable chronic mild stress (UCMS on exploratory, social and cognitive behavior of females of two inbred mouse strains (C57BL/6J and DBA/2J that differ in their dopaminergic profile. Exposure to chronic stress resulted in impaired circadian rhythmicity, sociability and social cognition in both inbred strains, but differentially affected activity patterns and contextual discrimination performance. These stress-induced behavioral impairments were accompanied by reduced expression levels of brain derived neurotrophic factor (BDNF in the prefrontal cortex. The strain-specific cognitive impairment was coexistent with enhanced plasma corticosterone levels and reduced expression of genes related to dopamine signaling in hippocampus. These results underline the importance of assessing different strains with multiple test batteries to elucidate the neural and genetic basis of social and cognitive impairments related to chronic stress.

Chronic stress associated with hypercaloric diet changes the hippocampal BDNF levels in male Wistar rats.

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Macedo, I C; Rozisky, J R; Oliveira, C; Oliveira, C M; Laste, G; Nonose, Y; Santos, V S; Marques, P R; Ribeiro, M F M; Caumo, W; Torres, I L S

2015-06-01

Chronic stress, whether associated with obesity or not, leads to different neuroendocrine and psychological changes. Obesity or being overweight has become one of the most serious worldwide public health problems. Additionally, it is related to a substantial increase in daily energy intake, which results in substituting nutritionally adequate meals for snacks. This metabolic disorder can lead to morbidity, mortality, and reduced quality of life. On the other hand, brain-derived neurotrophic factor (BDNF) is widely expressed in all brain regions, particularly in the hypothalamus, where it has important effects on neuroprotection, synaptic plasticity, mammalian food intake-behavior, and energy metabolism. BDNF is involved in many activities modulated by the hypothalamic-pituitary-adrenal (HPA) axis. Therefore, this study aims to evaluate the effect of obesity associated with chronic stress on the BDNF central levels of rats. Obesity was controlled by analyzing the animals' caloric intake and changes in body weight. As a stress parameter, we analyzed the relative adrenal gland weight. We found that exposure to chronic restraint stress during 12 weeks increases the adrenal gland weight, decreases the BDNF levels in the hippocampus and is associated with a decrease in the calorie and sucrose intake, characterizing anhedonia. These effects can be related stress, a phenomenon that induces depression-like behavior. On the other hand, the rats that received the hypercaloric diet had an increase in calorie intake and became obese, which was associated with a decrease in hypothalamus BDNF levels. Copyright © 2015. Published by Elsevier Ltd.

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

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

2016-09-01

Xiao-Chai-Hu-Tang (XCHT) has been proven to be effective for the clinical treatment of depression. However, the mechanisms of definite antidepressant-like effects and detailed metabolic biomarkers were still unclear in this prior study. Here, we have investigated the metabolic profiles and potential biomarkers in a chronic unpredictable mild stress model after treatment with XCHT. Metabonomics based on ultra-high performance liquid chromatography coupled with mass spectrometry was used to profile the metabolic fingerprints of serum obtained from a rat model with chronic unpredictable mild stress with and without XCHT treatment. The model rats showed a significant decrease in sucrose preference and food consumption, and these depression-like symptoms were significantly improved by XCHT. Through principal component analysis (PCA), nine potential biomarkers of tryptophan, uric acid, phenylalanine, cholic acid and lysophosphatidylcholine (C18:0 LPC, C16:0 LPC, C16:1 LPC, C18:1 LPC, C20:4 LPC) were characterized as potential biomarkers involved the pathogenesis of depression. The therapeutic effect of XCHT on depression may involve in amino acid metabolism, lipid metabolism, oxidative stress and inflammation response. The present investigation highlights that metabonomics is a valuable tool for studying the essence of depression as well as evaluating the efficacy of the corresponding drug treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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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.

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

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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. © 2014 International Life Sciences Institute.

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.

Stress-related clinical pain and mood in women with chronic pain: moderating effects of depression and positive mood induction.

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Davis, Mary C; Thummala, Kirti; Zautra, Alex J

2014-08-01

Chronic pain with comorbid depression is characterized by poor mood regulation and stress-related pain. This study aims to compare depressed and non-depressed pain patients in mood and pain stress reactivity and recovery, and test whether a post-stress positive mood induction moderates pain recovery. Women with fibromyalgia and/or osteoarthritis (N = 110) underwent interpersonal stress and were then randomly assigned by pain condition and depression status, assessed via the Center for Epidemiological Studies-Depression scale, to positive versus neutral mood induction. Depression did not predict stress-related reactivity in despondency, joviality, or clinical pain. However, depression × mood condition predicted recovery in joviality and clinical pain; depressed women recovered only in the positive mood condition, whereas non-depressed women recovered in both mood conditions. Depression does not alter pain and mood stress reactivity, but does impair recovery. Boosting post-stress jovial mood ameliorates pain recovery deficits in depressed patients, a finding relevant to chronic pain interventions.

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

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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. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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Darin J. Knapp

2016-07-01

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

The Direct and Interactive Effects of Neuroticism and Life Stress on the Severity and Longitudinal Course of Depressive Symptoms

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Brown, Timothy A.; Rosellini, Anthony J.

2011-01-01

The direct and interactive effects of neuroticism and stressful life events (chronic and episodic stressors) on the severity and temporal course of depression symptoms were examined in 826 outpatients with mood and anxiety disorders, assessed on three occasions over a one-year period (intake, 6- and 12-month follow-ups). Neuroticism, chronic stress, and episodic stress were uniquely associated with intake depression symptom severity. A significant interaction effect indicated that the strength of the effect of neuroticism on initial depression severity increased as chronic stress increased. Although neuroticism did not have a significant direct effect on the temporal course of depression symptoms, chronic stress significantly moderated this relationship such that neuroticism had an increasingly deleterious effect on depression symptom improvement as the level of chronic stress over follow-up increased. In addition, chronic stress over follow-up (but not episodic stress) was uniquely predictive of less depression symptom improvement. Consistent with a stress generation framework, however, initial depression symptom severity was positively associated with chronic stress during follow-up. The results are discussed in regard to diathesis-stress conceptual models of emotional disorders and the various roles of stressful life events in the onset, severity, and maintenance of depressive psychopathology. PMID:21381799

Anti-stress effects of transcutaneous electrical nerve stimulation (TENS) on colonic motility in rats.

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Yoshimoto, Sazu; Babygirija, Reji; Dobner, Anthony; Ludwig, Kirk; Takahashi, Toku

2012-05-01

Disorders of colonic motility may contribute to symptoms in patients with irritable bowel syndrome (IBS), and stress is widely believed to play a major role in developing IBS. Stress increases corticotropin releasing factor (CRF) of the hypothalamus, resulting in acceleration of colonic transit in rodents. In contrast, hypothalamic oxytocin (OXT) has an anti-stress effect via inhibiting CRF expression and hypothalamic-pituitary-adrenal axis activity. Although transcutaneous electrical nerve stimulation (TENS) and acupuncture have been shown to have anti-stress effects, the mechanism of the beneficial effects remains unknown. We tested the hypothesis that TENS upregulates hypothalamic OXT expression resulting in reduced CRF expression and restoration of colonic dysmotility in response to chronic stress. Male SD rats received different types of stressors for seven consecutive days (chronic heterotypic stress). TENS was applied to the bilateral hind limbs every other day before stress loading. Another group of rats did not receive TENS treatment. TENS significantly attenuated accelerated colonic transit induced by chronic heterotypic stress, which was antagonized by a central injection of an OXT antagonist. Immunohistochemical study showed that TENS increased OXT expression and decreased CRF expression at the paraventricular nucleus (PVN) following chronic heterotypic stress. It is suggested that TENS upregulates hypothalamic OXT expression which acts as an anti-stressor agent and mediates restored colonic dysmotility following chronic stress. TENS may be useful to treat gastrointestinal symptoms associated with stress.

The traditional drug Gongjin-Dan ameliorates chronic fatigue in a forced-stress mouse exercise model.

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Hong, Sung-Shin; Lee, Ji-Young; Lee, Jin-Seok; Lee, Hye-Won; Kim, Hyeong-Geug; Lee, Sam-Keun; Park, Bong-Ki; Son, Chang-Gue

2015-06-20

Gongjin-Dan is a representative traditional Oriental medicine herbal drug that has been used to treat chronic fatigue symptoms for several hundred years. We evaluated the anti-fatigue effects of Gongjin-Dan and the underlying mechanisms in a chronic forced exercise mouse model. Balb/C male mice underwent an extreme treadmill-based running stress (1-h, 5 days/week), and daily oral administration of distilled water, Gongjin-Dan (100, 200, or 400 mg/kg), or ascorbic acid (100 mg/kg) for 28 days. The anti-fatigue effects of Gongjin-Dan were evaluated with behavioral tests (exercise tolerance and swimming tests), and the corresponding mechanisms were investigated based on oxidative stress and inflammatory cytokine and stress hormone levels in skeletal muscle, sera, and brain tissue. Gongjin-Dan significantly increased exercise tolerance and latency times but reduced the number of electric shocks and immobilization time on the treadmill running and swimming tests, compared with the control group. Gongjin-Dan also significantly ameliorated alterations in oxidative stress-related biomarkers (reactive oxygen species and malondialdehyde), inflammatory cytokines (tumor necrosis factor-α, interleukin-1 beta, interleukin-6, and interferon-γ) and glycogen and L-lactate levels in skeletal muscle, compared with those in the control group. Moreover, Gongjin-Dan considerably normalized the forced running stress-induced changes in serum corticosterone and adrenaline levels, as well as brain serotonin level. These antioxidant and anti-stress effects of Gongjin-Dan were supported by the results of Western blotting (4-hydroxynonenal and heme oxygenase-1) and the gene expression levels (serotonin receptor and serotonin transporter). These results support the clinical relevance of Gongjin-Dan regarding anti-chronic fatigue properties. The underlying mechanisms involve attenuation of oxidative and inflammatory reactions in muscle and regulation of the stress response through the

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

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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. © 2010 Psychology Press, an imprint of the Taylor & Francis Group, an Informa business

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

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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

Chronic mild stress influences nerve growth factor through a matrix metalloproteinase-dependent mechanism.

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Kucharczyk, Mateusz; Kurek, Anna; Detka, Jan; Slusarczyk, Joanna; Papp, Mariusz; Tota, Katarzyna; Basta-Kaim, Agnieszka; Kubera, Marta; Lason, Wladyslaw; Budziszewska, Bogusława

2016-04-01

Stress is generally a beneficial experience that motivates an organism to action to overcome the stressful challenge. In particular situations, when stress becomes chronic might be harmful and devastating. The hypothalamus is a critical coordinator of stress and the metabolic response; therefore, disruptions in this structure may be a significant cause of the hormonal and metabolic disturbances observed in depression. Chronic stress induces adverse changes in the morphology of neural cells that are often associated with a deficiency of neurotrophic factors (NTFs); additionally, many studies indicate that insufficient NTF synthesis may participate in the pathogenesis of depression. The aim of the present study was to determine the expression of the nerve growth factor (NGF) in the hypothalamus of male rats subjected to chronic mild stress (CMS) or to prenatal stress (PS) and to PS in combination with an acute stress event (AS). It has been found that chronic mild stress, but not prenatal stress, acute stress or a combination of PS with AS, decreased the concentration of the mature form of NGF (m-NGF) in the rat hypothalamus. A discrepancy between an increase in the Ngf mRNA and a decrease in the m-NGF levels suggested that chronic mild stress inhibited NGF maturation or enhanced the degradation of this factor. We have shown that NGF degradation in the hypothalamus of rats subjected to chronic mild stress is matrix metalloproteinase-dependent and related to an increase in the active forms of some metalloproteinases (MMP), including MMP2, MMP3, MMP9 and MMP13, while the NGF maturation process does not seem to be changed. We suggested that activated MMP2 and MMP9 potently cleave the mature but not the pro- form of NGF into biologically inactive products, which is the reason for m-NGF decomposition. In turn, the enhanced expression of Ngf in the hypothalamus of these rats is an attempt to overcome the reduced levels of m-NGF. Additionally, the decreased level of m

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

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Chaby, Lauren E; Cavigelli, Sonia A; White, Amanda; Wang, Kayllie; Braithwaite, Victoria A

2013-01-01

Animals that experience adverse events in early life often have life-long changes to their physiology and behavior. Long-term effects of stress during early life have been studied extensively, but less attention has been given to the consequences of negative experiences solely during the adolescent phase. Adolescence is a particularly sensitive period of life when regulation of the glucocorticoid "stress" hormone response matures and specific regions in the brain undergo considerable change. 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 [F (1, 12) = 5.000, P 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 [T (1, 14) = 2.240, P = 0.04; T (1, 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.

Chronic Gestational Stress Leads to Depressive-Like Behavior and Compromises Medial Prefrontal Cortex Structure and Function during the Postpartum Period

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Leuner, Benedetta; Fredericks, Peter J.; Nealer, Connor; Albin-Brooks, Christopher

2014-01-01

Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC) is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC. PMID:24594708

Chronic gestational stress leads to depressive-like behavior and compromises medial prefrontal cortex structure and function during the postpartum period.

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Benedetta Leuner

Full Text Available Postpartum depression, which affects approximately 15% of new mothers, is associated with impaired mother-infant interactions and deficits in cognitive function. Exposure to stress during pregnancy is a major risk factor for postpartum depression. However, little is known about the neural consequences of gestational stress. The medial prefrontal cortex (mPFC is a brain region that has been linked to stress, cognition, maternal care, and mood disorders including postpartum depression. Here we examined the effects of chronic gestational stress on mPFC function and whether these effects might be linked to structural modifications in the mPFC. We found that in postpartum rats, chronic gestational stress resulted in maternal care deficits, increased depressive-like behavior, and impaired performance on an attentional set shifting task that relies on the mPFC. Furthermore, exposure to chronic stress during pregnancy reduced dendritic spine density on mPFC pyramidal neurons and altered spine morphology. Taken together, these findings suggest that pregnancy stress may contribute to postpartum mental illness and its associated symptoms by compromising structural plasticity in the mPFC.

Habitat disturbance results in chronic stress and impaired health status in forest-dwelling paleotropical bats.

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Seltmann, Anne; Czirják, Gábor Á; Courtiol, Alexandre; Bernard, Henry; Struebig, Matthew J; Voigt, Christian C

2017-01-01

Anthropogenic habitat disturbance is a major threat to biodiversity worldwide. Yet, before population declines are detectable, individuals may suffer from chronic stress and impaired immunity in disturbed habitats, making them more susceptible to pathogens and adverse weather conditions. Here, we tested in a paleotropical forest with ongoing logging and fragmentation, whether habitat disturbance influences the body mass and immunity of bats. We measured and compared body mass, chronic stress (indicated by neutrophil to lymphocyte ratios) and the number of circulating immune cells between several bat species with different roost types living in recovering areas, actively logged forests, and fragmented forests in Sabah, Malaysia. In a cave-roosting species, chronic stress levels were higher in individuals from fragmented habitats compared with conspecifics from actively logged areas. Foliage-roosting species showed a reduced body mass and decrease in total white blood cell counts in actively logged areas and fragmented forests compared with conspecifics living in recovering habitats. Our study highlights that habitat disturbance may have species-specific effects on chronic stress and immunity in bats that are potentially related to the roost type. We identified foliage-roosting species as particularly sensitive to forest habitat deterioration. These species may face a heightened extinction risk in the near future if anthropogenic habitat alterations continue.

Sodium Phenylbutyrate and Edaravone Abrogate Chronic Restraint Stress-Induced Behavioral Deficits: Implication of Oxido-Nitrosative, Endoplasmic Reticulum Stress Cascade, and Neuroinflammation.

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Jangra, Ashok; Sriram, Chandra Shaker; Dwivedi, Shubham; Gurjar, Satendra Singh; Hussain, Md Iftikar; Borah, Probodh; Lahkar, Mangala

2017-01-01

Chronic stress exposure can produce deleterious effects on the hippocampus (HC) which eventually leads to cognitive impairment and depression. Endoplasmic reticulum (ER) stress has been reported as one of the major culprits in the development of stress-induced cognitive impairment and depression. We investigated the neuroprotective efficacy of sodium phenylbutyrate (SPB), an ER stress inhibitor, and edaravone, a free radical scavenger, against chronic restraint stress (CRS)-induced cognitive deficits and anxiety- and depressive-like behavior in mice. Adult male Swiss albino mice were restrained for 6 h/day for 28 days and injected (i.p.) with SPB (40 and 120 mg/kg) or edaravone (3 and 10 mg/kg) for the last seven days. After stress cessation, the anxiety- and depressive-like behavior along with spatial learning and memory were examined. Furthermore, oxido-nitrosative stress, proinflammatory cytokines, and gene expression level of ER stress-related genes were assessed in HC and prefrontal cortex (PFC). CRS-exposed mice showed anxiety- and depressive-like behavior, which was significantly improved by SPB and edaravone treatment. In addition, SPB and edaravone treatment significantly alleviated CRS-induced spatial learning and memory impairment. Furthermore, CRS-evoked oxido-nitrosative stress, neuroinflammation, and depletion of Brain-derived neurotrophic factor were significantly ameliorated by SPB and edaravone treatment. We found significant up-regulation of ER stress-related genes in both HC and PFC regions, which were suppressed by SPB and edaravone treatment in CRS mice. Our study provides evidence that SPB and edaravone exerted neuroprotective effects on CRS-induced cognitive deficits and anxiety- and depressive-like behavior, which is possibly coupled with inhibition of oxido-nitrosative stress, neuroinflammation, and ER stress cascade.

Chronic water stress reduces tree growth and the carbon sink of deciduous hardwood forests.

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Brzostek, Edward R; Dragoni, Danilo; Schmid, Hans Peter; Rahman, Abdullah F; Sims, Daniel; Wayson, Craig A; Johnson, Daniel J; Phillips, Richard P

2014-08-01

Predicted decreases in water availability across the temperate forest biome have the potential to offset gains in carbon (C) uptake from phenology trends, rising atmospheric CO2 , and nitrogen deposition. While it is well established that severe droughts reduce the C sink of forests by inducing tree mortality, the impacts of mild but chronic water stress on forest phenology and physiology are largely unknown. We quantified the C consequences of chronic water stress using a 13-year record of tree growth (n = 200 trees), soil moisture, and ecosystem C balance at the Morgan-Monroe State Forest (MMSF) in Indiana, and a regional 11-year record of tree growth (n > 300 000 trees) and water availability for the 20 most dominant deciduous broadleaf tree species across the eastern and midwestern USA. We show that despite ~26 more days of C assimilation by trees at the MMSF, increasing water stress decreased the number of days of wood production by ~42 days over the same period, reducing the annual accrual of C in woody biomass by 41%. Across the deciduous forest region, water stress induced similar declines in tree growth, particularly for water-demanding 'mesophytic' tree species. Given the current replacement of water-stress adapted 'xerophytic' tree species by mesophytic tree species, we estimate that chronic water stress has the potential to decrease the C sink of deciduous forests by up to 17% (0.04 Pg C yr(-1) ) in the coming decades. This reduction in the C sink due to mesophication and chronic water stress is equivalent to an additional 1-3 days of global C emissions from fossil fuel burning each year. Collectively, our results indicate that regional declines in water availability may offset the growth-enhancing effects of other global changes and reduce the extent to which forests ameliorate climate warming. © 2014 John Wiley & Sons Ltd.

[Chronic fatigue and strategies of coping with occupational stress in police officers].

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Stepka, Ewa; Basińska, Małgorzata Anna

2014-01-01

Work as one of the most important activities in human life is related to stressful and difficult situations. Police officers make one of the many occupational groups that are particularly threatened by contact with a number of stressors. Therefore, their strategies of coping with stress are particularly important, because they play an important role in their functioning at work. The nature of the service as well as shift work and psychological costs incurred by police officers contribute to the emergence of chronic fatigue. The aim of this study was to evaluate the level of chronic fatigue in police officers and its relationship with the strategies of coping with occupational stress. A group of 61 police officers was examined. The following research methods were used: 1) Latack Coping Scale examining stress coping strategies at work (positive thinking, direct action, avoidance/resignation, seeking help, alcohol or stimulants use); 2) Mood Assessment Questionnaire CIS-20R examining the level of chronic fatigue and its components (subjective feeling of fatigue, impaired attention and concentration, reduced motivation, reduced activity); 3) Personal questionnaire providing socio-demographic data. It was found that the level of chronic fatigue in the group of the examined police officers was high (sten 8th). The most often used strategies of coping with stress were direct action and positive thinking, and the least often used strategy was the use of alcohol and stimulants. A significant negative correlation between the general level of chronic fatigue and the avoidance/resignation strategy was found. The results indicate that chronic fatigue is a problem affecting police officers and it is related to the stress coping strategies used.

Exposure to chronic mild stress prevents kappa opioid-mediated reinstatement of cocaine and nicotine place preference

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Ream eAl-Hasani

2013-08-01

Full Text Available Stress increases the risk of drug abuse, causes relapse to drug seeking, and potentiates the rewarding properties of both nicotine and cocaine. Understanding the mechanisms by which stress regulates the rewarding properties of drugs of abuse provides valuable insight into potential treatments for drug abuse. Prior reports have demonstrated that stress causes dynorphin release, activating kappa-opioid receptors (KOR in monoamine circuits resulting in both potentiation and reinstatement of cocaine and nicotine conditioned place preference. Here we report that kappa-opioid dependent reinstatement of cocaine and nicotine place preference is reduced when the mice are exposed to a randomized chronic mild stress regime prior to training in a conditioned place preference-reinstatement paradigm. The chronic mild stress schedule involves seven different stressors (removal of nesting for 24hr, 5min forced swim stress at 15°C, 8hr food and water deprivation, damp bedding overnight, white noise, cage tilt and disrupted home cage lighting rotated over a three-week period. This response is KOR-selective, because chronic mild stress does not protect against cocaine or nicotine drug-primed reinstatement. This protection from reinstatement is also observed following sub-chronic social defeat stress, where each mouse is placed in an aggressor mouse home cage for a period of 20 min over five days. In contrast, a single acute stressor resulted in a potentiation of KOR-induced reinstatement, similarly to previously reported. Prior studies have shown that stress alters sensitivity to opioids and prior stress can influence the pharmacodynamics of the opioid receptor system. Together, these findings suggest that exposure to different forms of stress may cause a dysregulation of kappa opioid circuitry and that changes resulting from mild stress can have protective and adaptive effects against drug relapse.

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

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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.

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

DEFF Research Database (Denmark)

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

2011-01-01

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

Impaired cardiac ischemic tolerance in spontaneously hypertensive rats is attenuated by adaptation to chronic and acute stress.

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Ravingerová, T; Bernátová, I; Matejíková, J; Ledvényiová, V; Nemčeková, M; Pecháňová, O; Tribulová, N; Slezák, J

2011-01-01

Chronic hypertension may have a negative impact on the myocardial response to ischemia. On the other hand, intrinsic ischemic tolerance may persist even in the pathologically altered hearts of hypertensive animals, and may be modified by short- or long-term adaptation to different stressful conditions. The effects of long-term limitation of living space (ie, crowding stress [CS]) and brief ischemia-induced stress on cardiac response to ischemia/reperfusion (I/R) injury are not yet fully characterized in hypertensive subjects. The present study was designed to test the influence of chronic and acute stress on the myocardial response to I/R in spontaneously hypertensive rats (SHR) compared with their effects in normotensive counterparts. In both groups, chronic, eight-week CS was induced by caging five rats per cage in cages designed for two rats (200 cm(2)/rat), while controls (C) were housed four to a cage in cages designed for six animals (480 cm(2)/rat). Acute stress was evoked by one cycle of I/R (5 min each, ischemic preconditioning) before sustained I/R in isolated Langendorff-perfused hearts of normotensive and SHR rats. At baseline conditions, the effects of CS were manifested only as a further increase in blood pressure in SHR, and by marked limitation of coronary perfusion in normotensive animals, while no changes in heart mechanical function were observed in any of the groups. Postischemic recovery of contractile function, severity of ventricular arrhythmias and lethal injury (infarction size) were worsened in the hypertrophied hearts of C-SHR compared with normotensive C. However, myo-cardial stunning and reperfusion-induced ventricular arrhythmias were attenuated by CS in SHR, which was different from deterioration of I/R injury in the hearts of normotensive animals. In contrast, ischemic preconditioning conferred an effective protection against I/R in both groups, although the extent of anti-infarct and anti-arrhythmic effects was lower in SHR. Both

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

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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.

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

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Marco D. Gulewitsch

2013-01-01

Full Text Available Aim. To investigate the degree of mental strain and chronic stress in a German community sample of students with IBS-like symptoms. Methods and Materials. Following an internet-based survey about stress, this study recruited 176 German university students (23.45±2.48 years; 48.3% males with IBS-like symptoms according to Rome III and 181 students without IBS (23.55±2.82 years; 50.3% males and compared them regarding current mental strain (SCL-90-R and the extend of chronic stress. Beyond this, IBS subtypes, IBS severity, and health care utilization were assessed. Results. Students fulfilling IBS criteria showed significantly elevated values of mental strain and chronic stress. Nearly 40% of the IBS group (versus 20% of the controls reached a clinically relevant value on the SCL-90-R global severity scale. IBS subtypes did not differ in terms of mental distress or chronic stress. Somatization, anxiety, and the chronic stressors “work overload,” “social tension,” and “dissatisfaction with job” were most closely connected to IBS symptom severity. Regarding health care utilization, our results show that consulting a physician frequently was not associated significantly with elevated mental strain or chronic stress but with IBS symptom severity. Conclusion. Our data contribute additional evidence to the distinct association between psychological stress and IBS in community samples.

Comfort food is comforting to those most stressed: evidence of the chronic stress response network in high stress women.

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Tomiyama, A Janet; Dallman, Mary F; Epel, Elissa S

2011-11-01

Chronically stressed rodents who are allowed to eat calorie-dense "comfort" food develop greater mesenteric fat, which in turn dampens hypothalamic-pituitary-adrenocortical (HPA) axis activity. We tested whether similar relations exist in humans, at least cross-sectionally. Fifty-nine healthy premenopausal women were exposed to a standard laboratory stressor to examine HPA response to acute stress and underwent diurnal saliva sampling for basal cortisol and response to dexamethasone administration. Based on perceived stress scores, women were divided into extreme quartiles of low versus high stress categories. We found as hypothesized that the high stress group had significantly greater BMI and sagittal diameter, and reported greater emotional eating. In response to acute lab stressor, the high stress group showed a blunted cortisol response, lower diurnal cortisol levels, and greater suppression in response to dexamethasone. These cross-sectional findings support the animal model, which suggests that long-term adaptation to chronic stress in the face of dense calories result in greater visceral fat accumulation (via ingestion of calorie-dense food), which in turn modulates HPA axis response, resulting in lower cortisol levels. Copyright © 2011 Elsevier Ltd. All rights reserved.

Chronic stress enhanced fear memories are associated with increased amygdala zif268 mRNA expression and are resistant to reconsolidation.

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Hoffman, Ann N; Parga, Alejandro; Paode, Pooja R; Watterson, Lucas R; Nikulina, Ella M; Hammer, Ronald P; Conrad, Cheryl D

2015-04-01

The chronically stressed brain may present a vulnerability to develop maladaptive fear-related behaviors in response to a traumatic event. In rodents, chronic stress leads to amygdala hyperresponsivity and dendritic hypertrophy and produces a post traumatic stress disorder (PTSD)-like phenotype that includes exaggerated fear learning following Pavlovian fear conditioning and resistance to extinction. It is unknown whether chronic stress-induced enhanced fear memories are vulnerable to disruption via reconsolidation blockade, as a novel therapeutic approach for attenuating exaggerated fear memories. We used a chronic stress procedure in a rat model (wire mesh restraint for 6h/d/21d) to create a vulnerable brain that leads to a PTSD-like phenotype. We then examined freezing behavior during acquisition, reactivation and after post-reactivation rapamycin administration (i.p., 40mg/kg) in a Pavlovian fear conditioning paradigm to determine its effects on reconsolidation as well as the subsequent functional activation of limbic structures using zif268 mRNA. Chronic stress increased amygdala zif268 mRNA during fear memory retrieval at reactivation. Moreover, these enhanced fear memories were unaffected by post reactivation rapamycin to disrupt long-term fear memory. Also, post-reactivation long term memory processing was also associated with increased amygdala (LA and BA), and decreased hippocampal CA1 zif268 mRNA expression. These results suggest potential challenges for reconsolidation blockade as an effective approach in treating exaggerated fear memories, as in PTSD. Our findings also support chronic stress manipulations combined with fear conditioning as a useful preclinical approach to study a PTSD-like phenotype. Copyright © 2015 Elsevier Inc. All rights reserved.

Protective effects of antidepressants against chronic fatigue syndrome-induced behavioral changes and biochemical alterations.

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Kumar, Anil; Garg, Ruchika

2009-02-01

Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities. The aim of this study was to explore the protective effects of antidepressants in an animal model of CFS in mice. Male albino mice were forced to swim individually for a period of 6-min session each for 7 days. Imipramine (10 and 20 mg/kg), desipramine (10 and 20 mg/kg) and citalopram (5 and 10 mg/kg) were administered 30 min before forced swimming test on each day. Various behavior tests (immobility time, locomotor activity, anxiety-like behavior by plus maze and mirror chamber) followed by biochemical parameters (lipid peroxidation, reduced glutathione, catalase and nitrite level) were assessed in chronic stressed mice. Chronic forced swimming for 7 days significantly caused increase in immobility period, impairment in locomotor activity, anxiety-like behavior, and oxidative stress (raised lipid peroxidation, nitrite activity and reduced glutathione and catalase activity) as compared with naïve mice (P immobility time, improved locomotor activity and anti-anxiety effect (in both plus maze and mirror chamber test), and attenuated oxidative stress in chronic stressed mice as compared with control (chronic fatigues) (P < 0.05). These results suggested that these drugs have protective effect and could be used in the management of chronic fatigue like conditions.

Chronic stress and peripheral pain: Evidence for distinct, region-specific changes in visceral and somatosensory pain regulatory pathways.

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Zheng, Gen; Hong, Shuangsong; Hayes, John M; Wiley, John W

2015-11-01

Chronic stress alters the hypothalamic-pituitary-adrenal (HPA) axis and enhances visceral and somatosensory pain perception. It is unresolved whether chronic stress has distinct effects on visceral and somatosensory pain regulatory pathways. Previous studies reported that stress-induced visceral hyperalgesia is associated with reciprocal alterations of endovanilloid and endocannabinoid pain pathways in DRG neurons innervating the pelvic viscera. In this study, we compared somatosensory and visceral hyperalgesia with respect to differential responses of peripheral pain regulatory pathways in a rat model of chronic, intermittent stress. We found that chronic stress induced reciprocal changes in the endocannabinoid 2-AG (increased) and endocannabinoid degradation enzymes COX-2 and FAAH (decreased), associated with down-regulation of CB1 and up-regulation of TRPV1 receptors in L6-S2 DRG but not L4-L5 DRG neurons. In contrast, sodium channels Nav1.7 and Nav1.8 were up-regulated in L4-L5 but not L6-S2 DRGs in stressed rats, which was reproduced in control DRGs treated with corticosterone in vitro. The reciprocal changes of CB1, TRPV1 and sodium channels were cell-specific and observed in the sub-population of nociceptive neurons. Behavioral assessment showed that visceral hyperalgesia persisted, whereas somatosensory hyperalgesia and enhanced expression of Nav1.7 and Nav1.8 sodium channels in L4-L5 DRGs normalized 3 days after completion of the stress phase. These data indicate that chronic stress induces visceral and somatosensory hyperalgesia that involves differential changes in endovanilloid and endocannabinoid pathways, and sodium channels in DRGs innervating the pelvic viscera and lower extremities. These results suggest that chronic stress-induced visceral and lower extremity somatosensory hyperalgesia can be treated selectively at different levels of the spinal cord. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress Management as an Adjunct to Physical Therapy for Chronic Neck Pain

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Bruflat, Angela K.; Balter, Jaclyn E.; McGuire, Denise; Fethke, Nathan B.

2012-01-01

Background and Purpose Chronic neck pain is prevalent in the workplace. Research suggests that psychosocial stress may contribute to the development of neck pain by causing excessive or prolonged muscle activity in some individuals. The purpose of this case report is to describe the rationale, development, and implementation of stress management as an adjunct to standard physical therapist management of chronic neck pain in a female office worker who responded to psychosocial stress with elevated muscle activity prior to treatment. Case Description A 44-year-old female office employee with an 8-year history of chronic neck pain participated in this case report. The patient was selected from a group of research participants who demonstrated elevated electromyographic (EMG) activity of the trapezius muscle in response to simulated occupational stressors. The multidisciplinary intervention consisted of 8 physical therapy sessions, supplemented by 8 stress management sessions that included EMG biofeedback and psychotherapy to facilitate muscle relaxation. Outcomes Neck disability decreased by 50%, trait anxiety decreased by 21%, and the duration of trapezius muscle rest in the workplace increased by 56% immediately after the 8-week intervention. These improvements were maintained 6 months after treatment, and the patient reported a complete absence of neck disability at the 2-year follow-up assessment. Discussion A sustained reduction in neck disability was observed for a patient with chronic neck pain after participating in a multidisciplinary intervention that combined physical therapy and stress management approaches to facilitate muscle relaxation in the workplace. Future clinical trials are needed to assess whether stress management is a useful adjunct therapy for patients with chronic neck pain who show elevated muscle activity in response to psychosocial stress. PMID:22700538

ProBDNF Signaling Regulates Depression-Like Behaviors in Rodents under Chronic Stress.

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Bai, Yin-Yin; Ruan, Chun-Sheng; Yang, Chun-Rui; Li, Jia-Yi; Kang, Zhi-Long; Zhou, Li; Liu, Dennis; Zeng, Yue-Qing; Wang, Ting-Hua; Tian, Chang-Fu; Liao, Hong; Bobrovskaya, Larisa; Zhou, Xin-Fu

2016-11-01

Chronic exposure to stressful environment is a key risk factor contributing to the development of depression. However, the mechanisms involved in this process are still unclear. Brain-derived neurotropic factor (BDNF) has long been investigated for its positive role in regulation of mood, although the role of its precursor, proBDNF, in regulation of mood is not known. In this study, using an unpredictable chronic mild stress (UCMS) paradigm we found that the protein levels of proBDNF were increased in the neocortex and hippocampus of stressed mice and this UCMS-induced upregulation of proBDNF was abolished by chronic administration of fluoxetine. We then established a rat model of UCMS and found that the expression of proBDNF/p75 NTR /sortilin was upregulated, whereas the expression of mature BDNF and TrkB was downregulated in both neocortex and hippocampus of chronically stressed rats. Finally, we found that the injection of anti-proBDNF antibody via intracerebroventricular (i.c.v.) and intraperitoneal (i.p.) approaches into the UCMS rats significantly reversed the stress-induced depression-like behavior and restored the exploratory activity and spine growth. Although intramuscular injection of AAV-proBDNF did not exacerbate the UCMS-elicited rat mood-related behavioral or pathological abnormalities, i.c.v. injection of AAV-proBDNF increased the depression-like behavior in naive rats. Our findings suggest that proBDNF plays a role in the development of chronic stress-induced mood disturbances in rodents. Central (i.c.v.) or peripheral (i.p.) inhibition of proBDNF by injecting specific anti-proBDNF antibodies may provide a novel therapeutic approach for the treatment of stress-related mood disorders.

Decreased MORF leads to prolonged endoplasmic reticulum stress in periodontitis-associated chronic inflammation.

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Xue, Peng; Li, Bei; An, Ying; Sun, Jin; He, Xiaoning; Hou, Rui; Dong, Guangying; Fei, Dongdong; Jin, Fang; Wang, Qintao; Jin, Yan

2016-11-01

The association between inflammation and endoplasmic reticulum (ER) stress has been described in many diseases. However, if and how chronic inflammation governs the unfolded protein response (UPR) and promotes ER homeostasis of chronic inflammatory disease remains elusive. In this study, chronic inflammation resulted in ER stress in mesenchymal stem cells in the setting of periodontitis. Long-term proinflammatory cytokines induced prolonged ER stress and decreased the osteogenic differentiation of periodontal ligament stem cells (PDLSCs). Interestingly, we showed that chronic inflammation decreases the expression of lysine acetyltransferase 6B (KAT6B, also called MORF), a histone acetyltransferase, and causes the upregulation of a key UPR sensor, PERK, which lead to the persistent activation of the UPR in PDLSCs. Furthermore, we found that the activation of UPR mediated by MORF in chronic inflammation contributes to the PERK-related deterioration of the osteogenic differentiation of PDLSCs both in vivo and in vitro. Taken together, our results suggest that chronic inflammation compromises UPR function through MORF-mediated-PERK transcription, which is a previously unrecognized mechanism that contributes to impaired ER function, prolonged ER stress and defective osteogenic differentiation of PDLSCs in periodontitis.

Chronic Stress in Adolescents and Its Neurobiological and Psychopathological Consequences: An RDoC Perspective.

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Sheth, Chandni; McGlade, Erin; Yurgelun-Todd, Deborah

2017-01-01

The Research Domain Criteria (RDoC) initiative provides a strategy for classifying psychopathology based on behavioral dimensions and neurobiological measures. Neurodevelopment is an orthogonal dimension in the current RDoC framework; however, it has not yet been fully incorporated into the RDoC approach. A combination of both a neurodevelopmental and RDoC approach offers a multidimensional perspective for understanding the emergence of psychopathology during development. Environmental influence (e.g., stress) has a profound impact on the risk for development of psychiatric illnesses. It has been shown that chronic stress interacts with the developing brain, producing significant changes in neural circuits that eventually increase the susceptibility for development of psychiatric disorders. This review highlights effects of chronic stress on the adolescent brain, as adolescence is a period characterized by a combination of significant brain alterations, high levels of stress, and emergence of psychopathology. The literature synthesized in this review suggests that chronic stress-induced changes in neurobiology and behavioral constructs underlie the shared vulnerability across a number of disorders in adolescence. The review particularly focuses on depression and substance use disorders; however, a similar argument can also be made for other psychopathologies, including anxiety disorders. The summarized findings underscore the need for a framework to integrate neurobiological findings from disparate psychiatric disorders and to target transdiagnostic mechanisms across disorders.

Chronic social isolation and chronic variable stress during early development induce later elevated ethanol intake in adult C57BL/6J mice.

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Lopez, Marcelo F; Doremus-Fitzwater, Tamara L; Becker, Howard C

2011-06-01

Experience with stress situations during early development can have long-lasting effects on stress- and anxiety-related behaviors. Importantly, this can also favor drug self-administration. These studies examined the effects of chronic social isolation and/or variable stress experiences during early development on subsequent voluntary ethanol intake in adult male and female C57BL/6J mice. The experiments were conducted to evaluate the effect of chronic isolation between weaning and adulthood (Experiment 1), chronic isolation during adulthood (Experiment 2), and chronic variable stress (CVS) alone or in combination with chronic social isolation between weaning and adulthood (Experiment 3) on subsequent voluntary ethanol intake. Mice were born in our facility and were separated into two housing conditions: isolate housed (one mouse/cage) or group housed (four mice/cage) according to sex. Separate groups were isolated for 40 days starting either at time of weaning postnatal day 21 (PD 21) (early isolation, Experiments 1 and 3) or at adulthood (PD 60: late isolation, Experiment 2). The effects of housing condition on subsequent ethanol intake were assessed starting at around PD 65 in Experiments 1 and 3 or PD 105 days in Experiment 2. In Experiment 3, starting at PD 32, isolate-housed and group-housed mice were either subjected to CVS or left undisturbed. CVS groups experienced random presentations of mild stressors for 14 days, including exposure to an unfamiliar open field, restraint, physical shaking, and forced swim, among others. All mice were tested for ethanol intake for 14 days using a two-bottle choice (ethanol 15% vol/vol vs. water) for a 2-h limited access procedure. Early social isolation resulted in greater ethanol intake compared with the corresponding group-housed mice (Experiment 1). In contrast, social isolation during adulthood (late isolation) did not increase subsequent ethanol intake compared with the corresponding group-housed mice (Experiment 2

Effects of different timing of stress on corticosterone, BDNF and memory in male rats.

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

2015-02-01

Learning and memory seem to be affected by chronic stress. Previous reports have considered chronic stress as a precipitating factor of different neuropsychological disorders, while others reported neurobiological adaptations following stress. The present study investigated the effects of chronic stress before, after, and during learning on the changes of learning and memory, on serum and hippocampal levels of corticosterone (CORT), brain-derived neurotrophic factor (BDNF) and body weight in rats. Male Wistar rats were randomly divided into four groups (n=10) including Control (Co), Stress-Learning-Rest (St-L-Re), Rest-Learning-Stress (Re-L-St), and Stress-Learning-Stress (St-L-St) groups. The chronic restraint stress was applied 6 h/day for 21 days. Moreover, the passive avoidance test was used to assess memory deficit, 1, 7, and 21 days after training. At the end of experiments, CORT and BDNF levels were measured. The findings did not support adaptation in chronic stress conditions. The acquisition time as well as the short and mid-term memories was significantly impaired in the St-L-Re group. Short, mid, and long-term memories were significantly impaired in the Re-L-St and St-L-St groups compared with the Co group, as a result of the enhancement of CORT and reduction of BDNF levels. In the St-L-St group, changes in memory functions were less pronounced than in the Re-L-St group. Also, body weight declined following the chronic stress, while recovery period enhanced the body weight gain in stressed rats. It can be concluded that a potential time-dependent involvement of stress and recovery period on the level of BDNF. Longer duration time of chronic stress might promote adaptive effects on memory and CORT level. Copyright © 2014 Elsevier Inc. All rights reserved.

Ocimum basilicum improve chronic stress-induced neurodegenerative changes in mice hippocampus.

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Ayuob, Nasra Naeim; El Wahab, Manal Galal Abd; Ali, Soad Shaker; Abdel-Tawab, Hanem Saad

2018-01-22

Alzheimer's disease (AD), one of the progressive neurodegenerative diseases might be associated with exposure to stress and altered living conditions. This study aimed to evaluate the effectiveness of Ocimum basilicum (OB) essential oils in improving the neurodegenerative-like changes induced in mice after exposed to chronic unpredictable mild stress (CUMS). Forty male Swiss albino mice divided into four groups (n = 10); the control, CUMS, CUMS + Fluoxetine, CUMS + OB were used. Behavioral tests, serum corticosterone level, hippocampus protein level of the glucocorticoid receptors (GRs) and brain-dreived neurotropic factor (BDNF) were determined after exposure to CUMS. Hippocampus was histopathologically examined. Data were analyzed using statistical package for the social sciences (SPSS) and P value of less than 0.05 was considered significant. OB diminished the depression manifestation as well as impaired short term memory observed in the mice after exposure to the CUMS as evidenced by the forced swimming and elevated plus maze test. OB also up-regulated the serum corticosterone level, hippocampal protein level of the glucocorticoid receptor and the brain-derived neurotropic factor and reduced the neurodegenerative and atrophic changes induced in the hippocampus after exposure to CUMS. Essential oils of OB alleviated the memory impairment and hippocampal neurodegenerative changes induced by exposure to the chronic unpredictable stress indicating that it is the time to test its effectiveness on patients suffering from Alzheimer disease.

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.

Impact of chronic and acute academic stress on lymphocyte subsets and monocyte function.

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Viktoriya Maydych

Full Text Available This study investigated the effects of a temporally confined naturalistic stressor (academic stress on immune functions. Furthermore, moderating influences of a number of psychological variables were assessed. Five blood samples were obtained from 20 students during an observation period of 8 weeks, starting 4.5 weeks before an exam period up to 1 week following the last exam. The analysis of 45 immune parameters revealed several time-dependent changes attributable to examination stress. We observed a reduction in the absolute numbers of natural killer (NK cells and monocytes in peripheral blood and a shift towards more immature and naïve cells within NK and T cell populations. In addition, IL-6 and TNF-α production by LPS-stimulated monocytes was increased. Psychological variables were grouped by means of factor analyses into two factors. One factor, which was interpreted as an indication of chronic stress, moderated the relationships between academic stress and percentages of mature CD57+ NK cells. This chronic stress factor was also associated with an increase in memory and a decrease in naïve CD8 T cells and increased serum levels of IL-17. The present study identifies important potential psychological mediators of stress-induced changes in specific immunological parameters.

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

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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.

An aberrant parasympathetic response: a new perspective linking chronic stress and itch.

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Kim, Hei Sung; Yosipovitch, Gil

2013-04-01

Perceived stress has long been known to alter the dynamic equilibrium established between the nervous, endocrine and immune system and is widely recognised to trigger or enhance pruritus. However, the exact mechanism of how the major stress response systems, such as the hypothalamus-pituitary adrenal (HPA) axis and the autonomic nervous system induce or aggravate chronic itch, has not been elucidated. The limbic regions of the brain such as the prefrontal cortex and hippocampus are deeply involved in the regulation of the stress response and intersect with circuits that are responsible for memory and reward. According to the 'Polyvagal Theory', certain limbic structures that serve as a 'higher brain equivalent of the parasympathetic nervous system' play a foremost role in maintaining body homoeostasis by functioning as an active vagal brake. In addition, the limbic system has been postulated to regulate two distinct, yet related aspects of itch: (i) the sensory-discriminative aspect; and (ii) the affective-cognitive aspect. Chronic stress-induced itch is hypothesised to be caused by stress-related changes in limbic structure with subsequent rewiring of both the peripheral and central pruriceptive circuits. Herein, we review data suggesting that a dysfunctional parasympathetic nervous system associated with chronic stress may play a critical role in the regulatory control of key candidate molecules, receptors and brain structures involved in chronic itch. © 2012 John Wiley & Sons A/S.

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

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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. Copyright © 2015. Published by Elsevier Inc.

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.

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

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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.

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

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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...

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

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

2014-01-01

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

Effects of chronic restraint stress on social behaviors and the number of hypothalamic oxytocin neurons in male rats.

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Li, Jin; Li, Han-Xia; Shou, Xiao-Jing; Xu, Xin-Jie; Song, Tian-Jia; Han, Song-Ping; Zhang, Rong; Han, Ji-Sheng

2016-12-01

Oxytocin (OXT) and vasopressin (AVP) are considered to be related to mammalian social behavior and the regulation of stress responses. The present study investigated the effects of chronic homotypic restraint stress (CHRS) on social behaviors and anxiety, as well as its repercussions on OXT- and AVP-positive neurons in the paraventricular nucleus (PVN) and supraoptic nucleus (SON) nuclei in rat. Male Sprague-Dawley rats receiving CHRS were exposed to repeated restraint stress of 30min per day for 10days. Changes in social approach behaviors were evaluated with the three-chambered social approach task. Changes in anxiety-like behaviors were evaluated in the light-dark box test. The number of neurons expressing oxytocin and/or vasopressin in PVN and SON were examined by immunohistochemistry techniques. The results demonstrated that social approach was increased and anxiety was decreased following 10-day exposure to CHRS. Furthermore, the number of OXT-immunoreactive cells in PVN was increased significantly, whereas no change in SON was seen. The number of AVP immunoreactive cells either in PVN or SON was unaffected. The results of this study suggest that certain types of stress could be effective in the treatment of social dysfunction in persons with mental disorders such as autism, social anxiety disorder. The therapeutic effects may be mediated by changes in the function of OXT neurons in PVN. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synergist effects of n-acetylcysteine and deferoxamine treatment on behavioral and oxidative parameters induced by chronic mild stress in rats.

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Arent, Camila O; Réus, Gislaine Z; Abelaira, Helena M; Ribeiro, Karine F; Steckert, Amanda V; Mina, Francielle; Dal-Pizzol, Felipe; Quevedo, João

2012-12-01

A growing body of evidence has pointed to a relationship between oxidative stress and depression. Thus, the present study was aimed at evaluating the effects of the antioxidants n-acetylcysteine (NAC), deferoxamine (DFX) or their combination on sweet food consumption and oxidative stress parameters in rats submitted to 40days of exposure to chronic mild stress (CMS). Our results showed that in stressed rats treated with saline, there was a decrease in sweet food intake and treatment with NAC or NAC in combination with DFX reversed this effect. Treatment with NAC and DFX decreased the oxidative damage, which include superoxide and TBARS production in submitochondrial particles, and also thiobarbituric acid reactive substances (TBARS) levels and carbonyl proteins in the prefrontal cortex, amygdala and hippocampus. Treatment with NAC and DFX also increased the activity of the antioxidant enzymes, superoxide dismutase and catalase in the same brain areas. Even so, a combined treatment with NAC and DFX produced a stronger increase of antioxidant activities in the prefrontal cortex, amygdala and hippocampus. The results described here indicate that co-administration may induce a more pronounced antidepressant activity than each treatment alone. In conclusion, these results suggests that treatment with NAC or DFX alone or in combination on oxidative stress parameters could have positive effects against neuronal damage caused by oxidative stress in major depressive disorders. Copyright © 2012 Elsevier Ltd. All rights reserved.

Hyperoside protects against chronic mild stress-induced learning and memory deficits.

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Gong, Yeli; Yang, Youhua; Chen, Xiaoqing; Yang, Min; Huang, Dan; Yang, Rong; Zhou, Lianying; Li, Changlei; Xiong, Qiuju; Xiong, Zhe

2017-07-01

Hyperoside (quercetin-3-O-b-d-galactosidepyranose) is a plant-derived flavonoid mainly found in fruits, fruit juices (most notably flavanols, flavanones, and anthocyanins) and Chinese traditional medicines. It has been applied to relieve pain and improve cardiovascular functions in clinic. However, the effects of hyperoside on cognitive impairment induced by chronic stress and the underlying molecular mechanisms remain unclear. In the current study, we used chronic mild stress (CMS) rats to investigate the effects of hyperoside on learning and memory and further explore the possible mechanisms. Our results demonstrated that hyperoside reduced the escape latency and the swimming distance of CMS rats in Morris water maze test and reversed depressive symptoms in forced swim test (FST) and sucrose preference test. In addition, hyperoside increased the expression of brain-derived neurotrophic factor (BDNF) in hippocampus of CMS rats without influencing the corticosterone (CORT) level in blood plasma. Furthermore, K252a, an inhibitor of the BDNF receptor TrkB, prevented the protective effects of hyperoside on learning and memory in CMS rats. Taken together, these results indicate that hyperoside reverses the cognitive impairment induced by CMS, which is associated with the regulation of BDNF signaling pathway. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chronic psychosocial stress disturbs long-bone growth in adolescent mice

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Sandra Foertsch

2017-12-01

Full Text Available Although a strong association between psychiatric and somatic disorders is generally accepted, little is known regarding the interrelationship between mental and skeletal health. Although depressive disorders have been shown to be strongly associated with osteoporosis and increased fracture risk, evidence from post-traumatic stress disorder (PTSD patients is less consistent. Therefore, the present study investigated the influence of chronic psychosocial stress on bone using a well-established murine model for PTSD. C57BL/6N mice (7 weeks old were subjected to chronic subordinate colony housing (CSC for 19 days, whereas control mice were singly housed. Anxiety-related behavior was assessed in the open-field/novel-object test, after which the mice were euthanized to assess endocrine and bone parameters. CSC mice exhibited increased anxiety-related behavior in the open-field/novel-object test, increased adrenal and decreased thymus weights, and unaffected plasma morning corticosterone. Microcomputed tomography and histomorphometrical analyses revealed significantly reduced tibia and femur lengths, increased growth-plate thickness and reduced mineral deposition at the growth plate, suggesting disturbed endochondral ossification during long-bone growth. This was associated with reduced Runx2 expression in hypertrophic chondrocytes in the growth plate. Trabecular thicknesses and bone mineral density were significantly increased in CSC compared to singly housed mice. Tyrosine hydroxylase expression was increased in bone marrow cells located at the growth plates of CSC mice, implying that local adrenergic signaling might be involved in the effects of CSC on the skeletal phenotype. In conclusion, chronic psychosocial stress negatively impacts endochondral ossification in the growth plate, affecting both longitudinal and appositional bone growth in adolescent mice.

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

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

2008-01-01

In this study, we examined whether chronic stress in adulthood can exert long-term effects on spatial-cognitive abilities and on the survival of newborn hippocampal cells in aging animals. Male Wistar rats were subjected to chronic unpredictable stress at midlife (12 months old) and then reexposed...... in the hippocampus. Interestingly, spatial-memory performance in the Morris water maze was positively correlated with the number of newborn cells that survived in the dentate gyrus: better spatial memory in the water maze was associated with more 5-bromo-2-deoxyuridine (BrdU)-labeled cells. Administration of FGL......, a peptide mimetic of neural cell adhesion molecule, during the 4 weeks of continuous stress not only prevented the deleterious effects of chronic stress on spatial memory, but also reduced the survival of the newly generated hippocampal cells in aging animals. FGL treatment did not, however, prevent...

The effect of chronic ozone exposure on the activation of endoplasmic reticulum stress and apoptosis in rat hippocampus

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Erika Rodríguez-Martínez

2016-10-01

Full Text Available The chronic exposure to low doses of ozone, like in environmental pollution, leads to a state of oxidative stress, which has been proposed to contribute to neurodegenerative disorders, including Alzheimer's disease. It induces an increase of calcium in the endoplasmic reticulum (ER, which produces ER stress. On the other hand, different studies show that, in diseases such as Alzheimer’s, there exist disturbances in protein folding where ER plays an important role. The objective of this study was to evaluate the state of chronic oxidative stress on ER stress and its relationship with apoptotic death in the hippocampus of rats exposed to low doses of ozone. We used 108 male Wistar rats randomly divided into five groups. The groups received one of the following treatments: 1 Control (air, 2 Ozone (O3 7 days, 3 O3 15 days, 4 O3 30 days, 5 O3 60 days, and 6 O3 90 days. Two hours after each treatment, the animals were sacrificed and the hippocampus was extracted. Afterwards, the tissue was processed for western blot and immunohistochemistry using the following antibodies: ATF6, GRP8 and caspase 12. It was also performed TUNEL assay and electronic microscopy. Our results show an increase in ATF6, GRP78 and caspase 12 as well as ER ultrastructural alterations and an increase of TUNEL positive cells after 60 and 90 days of exposure to ozone. With the obtained results, we can conclude that oxidative stress induced by chronic exposure to low doses of ozone leads to ER stress. ER stress activates ATF6 inducing the increase of GRP78 in the cytoplasm, which leads to the increase in the nuclear translocation of ATF6. Finally, the translocation creates a vicious cycle that, together with the activation of the cascade for apoptotic cell death, contributes to the maintenance of ER stress. These events potentially contribute in the neurodegeneration processes in diseases like Alzheimer’s Disease.

Family-School Strategies for Responding to the Needs of Children Experiencing Chronic Stress

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Swick, Kevin J.; Knopf, Herman; Williams, Reginald; Fields, M. Evelyn

2013-01-01

Children experience chronic stress in ways that can impair their brain functioning and overall development. This article articulates the unique needs of children experiencing chronic stress and discusses strategies that families and schools can use to support and strengthen children's development across the social, emotional, and cognitive domains.

Cytoprotective Effects of Pumpkin (Cucurbita Moschata) Fruit Extract against Oxidative Stress and Carbonyl Stress.

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Shayesteh, Reyhaneh; Kamalinejad, Mohammad; Adiban, Hasan; Kardan, Azin; Keyhanfar, Fariborz; Eskandari, Mohammad Reza

2017-10-01

Background Diabetes mellitus is a chronic endocrine disorder that is associated with significant mortality and morbidity due to microvascular and macrovascular complications. Diabetes complications accompanied with oxidative stress and carbonyl stress in different organs of human body because of the increased generation of free radicals and impaired antioxidant defense systems. In the meantime, reactive oxygen species (ROS) and reactive carbonyl species (RCS) have key mediatory roles in the development and progression of diabetes complications. Therapeutic strategies have recently focused on preventing such diabetes-related abnormalities using different natural and chemical compounds. Pumpkin ( Cucurbita moschata ) is one of the most important vegetables in the world with a broad-range of pharmacological activities such as antihyperglycemic effect. Methods In the present study, the cytoprotective effects of aqueous extract of C. moschata fruit on hepatocyte cytotoxicity induced by cumene hydroperoxide (oxidative stress model) or glyoxal (carbonylation model) were investigated using freshly isolated rat hepatocytes. Results The extract of C. moschata (50 μg/ml) excellently prevented oxidative and carbonyl stress markers, including hepatocyte lysis, ROS production, lipid peroxidation, glutathione depletion, mitochondrial membrane potential collapse, lysosomal damage, and cellular proteolysis. In addition, protein carbonylation was prevented by C. moschata in glyoxal-induced carbonyl stress. Conclusion It can be concluded that C. moschata has cytoprotective effects in oxidative stress and carbonyl stress models and this valuable vegetable can be considered as a suitable herbal product for the prevention of toxic subsequent of oxidative stress and carbonyl stress seen in chronic hyperglycemia. © Georg Thieme Verlag KG Stuttgart · New York.

Effect of different periods of chronic heat stress with or without vitamin C supplementation on bone and selected serum parameters of broiler chickens.

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Mosleh, Najmeh; Shomali, Tahoora; Nematollahi, Fahimeh; Ghahramani, Zahra; Ahrari Khafi, Mohammad Saeid; Namazi, Fatemeh

2018-04-01

This study evaluates the effect of different periods of chronic heat stress (CHS) on selected bone and serum parameters of broiler chickens with or without vitamin C administration. Ninety 23-day-old chickens were randomly allocated into seven groups: (1) control, (2) short-term CHS (5 days), (3) short-term CHS + vitamin C (12 g/100 l drinking water of a 50% product), (4) medium-term CHS (10 days), (5) medium-term CHS + vitamin C, (6) long-term CHS (20 days) and (7) long-term CHS + vitamin C. In heat-stressed groups the temperature was increased to 39 ± 1°C for 8 h/day. At the end of the experiment, blood samples were collected and shank, keel and tibia bones were removed. CHS was not associated with a drastic change in serum Ca and corticosterone, or bone characteristics (both cortical and trabecular bones in radiographical and histological evaluation), or birds' performance. Oxidative stress was present especially with short-term CHS. CHS, especially for short or medium periods, showed a tendency to increase serum vitamin C and administration of this vitamin did not make a significant change in its serum levels although it ameliorated oxidative stress. In conclusion, it seems that CHS is not associated with an appreciable change in broiler performance, bone characteristics, or selected serum parameters; and simultaneous vitamin C administration at the dosage of 12 g/100 l in drinking water has no beneficial effect apart from reducing oxidative stress especially in short-term chronically heat-stressed birds.

Possible role of oxidative stress and immunological activation in mouse model of chronic fatigue syndrome and its attenuation by olive extract.

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Gupta, Amit; Vij, Garima; Chopra, Kanwaljit

2010-09-14

Various putative theories involved in the development of chronic fatigue syndrome revolve around the role of stress, infection and oxidative stress. Scientific evidence highlighting the protective role of nutritional supplements in chronic fatigue syndrome is lacking. Based on these assumptions, the present study was designed to evaluate the effect of olive extract in a mouse model of immunologically-induced fatigue, wherein purified lipopolysaccharide (LPS) and Brucella abortus (BA) antigen were used as immunogens. The assessment of chronic fatigue syndrome was based on immobility period during chronic water-immersion stress test for 10 min daily. The stress-induced hyperalgesia was measured by tail withdrawal latency. Mice challenged with LPS or BA for 19 days showed significant increase in the immobility time, hyperalgesia and oxidative stress on the 19th day. Serum tumor necrosis factor-alpha (TNF-α) levels were also markedly increased with LPS or BA challenge. Concurrent treatment with olive extract resulted in a significant decrease in the immobility time as well as hyperalgesia. There was significant attenuation of oxidative stress as well as serum TNF-α levels. The results of the present study strongly indicate the role of oxidative stress and immunological activation in the pathophysiology of chronic fatigue syndrome and highlight the valuable role of olive extract in combating chronic fatigue syndrome. Copyright © 2010 Elsevier B.V. All rights reserved.

Association of stress and depression with chronic facial pain: A case-control study based on the Northern Finland 1966 Birth Cohort.

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Nevalainen, Netta; Lähdesmäki, Raija; Mäki, Pirjo; Ek, Ellen; Taanila, Anja; Pesonen, Paula; Sipilä, Kirsi

2017-05-01

The aim was to study the association between stress level and chronic facial pain, while controlling for the effect of depression on this association, during a three-year follow-up in a general population-based birth cohort. In the general population-based Northern Finland 1966 Birth Cohort, information about stress level, depression and facial pain were collected using questionnaires at the age of 31 years. Stress level was measured using the Work Ability Index. Depression was assessed using the 13-item depression subscale in the Hopkins Symptom Checklist-25. Three years later, a subsample of 52 subjects (42 women) with chronic facial pain and 52 pain-free controls (42 women) was formed. Of the subjects having high stress level at baseline, 73.3% had chronic facial pain, and 26.7% were pain-free three years later. The univariate logistic regression analysis showed that high stress level at 31 years increased the risk for chronic facial pain (crude OR 6.1, 95%, CI 1.3-28.7) three years later. When including depression in a multivariate model, depression associated statistically significantly with chronic facial pain (adjusted OR 2.5, 95%, CI 1.0-5.8), whereas stress level did not (adjusted OR 2.3, 95%, CI 0.6-8.4). High stress level is connected with increased risk for chronic facial pain. This association seems to mediate through depression.

STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

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Dewi-Nurul M Dewi-Nurul

2006-04-01

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

3, 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.

Experimental studies on possible regulatory role of nitric oxide on the differential effects of chronic predictable and unpredictable stress on adaptive immune responses.

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Thakur, Tarun; Gulati, Kavita; Rai, Nishant; Ray, Arunabha

2017-09-01

The present study was designed to investigate the effects of chronic predictable stress (CPS) and chronic unpredictable stress (CUS) on immunological responses in KLH-sensitized rats and involvement of NOergic signaling pathways mediating such responses. Male Wistar rats (200-250g) were exposed to either CPS or CUS for 14days and IgG antibody levels and delayed type hypersensitivity (DTH) response was determined to assess changes in adaptive immunity. To evaluate the role of nitric oxide during such immunomodulation, biochemical estimation of stable metabolite of nitric oxide (NOx) and 3-nitrotyrosine (3-NT, a marker of peroxynitrite formation) were done in both blood and brain. Chronic stress exposure resulted in suppression of IgG and DTH response and elevated NOx and 3-NT levels, with a difference in magnitude of response in CPS vs CUS. Pretreatment with aminoguanidine (iNOS inhibitor) caused further reduction of adaptive immune responses and attenuated the increased NOx and 3-NT levels in CPS or CUS exposed rats. On the other hand 7-NI (nNOS inhibitor) did not significantly affect these estimated parameters. The results suggest involvement of iNOS and lesser/no role of nNOS during modulation of adaptive immunity to stress. Thus, the result showed that predictability of stressors results in differential degree of modulation of immune responses and complex NO-mediated signaling mechanisms may be involved during responses. Copyright © 2017. Published by Elsevier B.V.

Adaptogenic potential of royal jelly in liver of rats exposed to chronic stress.

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Douglas Carvalho Caixeta

Full Text Available Restraint and cold stress increase both corticosterone and glycemia, which lead to oxidative damages in hepatic tissue. This study assessed the effect of royal jelly (RJ supplementation on the corticosterone level, glycemia, plasma enzymes and hepatic antioxidant system in restraint and cold stressed rats. Wistar rats were allocated into no-stress, stress, no-stress supplemented with RJ and stress supplemented with RJ groups. Initially, RJ (200mg/Kg was administered for fourteen days and stressed groups were submitted to chronic stress from the seventh day. The results showed that RJ supplementation decreases corticosterone levels and improves glycemia control after stress induction. RJ supplementation also decreased the body weight, AST, ALP and GGT. Moreover, RJ improved total antioxidant capacity, SOD activity and reduced GSH, GR and lipoperoxidation in the liver. Thus, RJ supplementation reestablished the corticosterone levels and the hepatic antioxidant system in stressed rats, indicating an adaptogenic and hepatoprotective potential of RJ.

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

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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.

How does early maternal separation and chronic stress in adult rats affect the immunoreactivity of serotonergic neurons within the dorsal raphe nucleus?

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Pollano, Antonella; Trujillo, Verónica; Suárez, Marta M

2018-01-01

Vulnerability to emotional disorders like depression derives from interactions between early and late environments, including stressful conditions. The serotonin (5HT) system is strongly affected by stress and chronic unpredictable stress can alter the 5HT system. We evaluated the distribution of active serotonergic neurons in the dorsal raphe nucleus (DR) through immunohistochemistry in maternally separated and chronically stressed rats treated with an antidepressant, tianeptine, whose mechanism of action is still under review. Male Wistar rats were subjected to daily maternal separation (MS) for 4.5 h between postnatal days (PND) 1-21, or to animal facility rearing (AFR). Between (PND) days 50-74, rats were exposed to chronic unpredictable stress and were treated daily with tianeptine (10 mg/kg) or vehicle. We found an interaction between the effects of MS and chronic unpredictable stress on Fos-5HT immunoreactive cells at mid-caudal level of the DR. MS-chronically stressed rats showed an increase of Fos-5HT immunoreactive cells compared with AFR-chronically stressed rats. The ventrolateral (DRL/VLPAG) and dorsal (DRD) subdivisions of the DR were significantly more active than the ventral part (DRV). At the rostral level of the DR, tianeptine decreased the number of Fos-5HT cells in DR in the AFR groups, both unstressed and stressed. Overall, our results support the idea of a match in phenotype exhibited when the early and the adult environment correspond.

Examining within- and across-day relationships between transient and chronic stress and parent food-related parenting practices in a racially/ethnically diverse and immigrant population : Stress types and food-related parenting practices.

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Berge, Jerica M; Tate, Allan; Trofholz, Amanda; Fertig, Angela; Crow, Scott; Neumark-Sztainer, Dianne; Miner, Michael

2018-01-16

Although prior research suggests that stress may play a role in parent's use of food-related parenting practices, it is unclear whether certain types of stress (e.g., transient, chronic) result in different food-related parenting practices. Identifying whether and how transient (i.e., momentary; parent/child conflict) and chronic (i.e., long-term; unemployment >6 months) sources of stress are related to parent food-related parenting practices is important with regard to childhood obesity. This is particularly important within racially/ethnically diverse parents who may be more likely to experience both types of stress and who have higher levels of obesity and related health problems. The current study examined the association between transient and chronic stressors and food-related parenting practices in a racially/ethnically diverse and immigrant sample. The current study is a cross-sectional, mixed-methods study using ecological momentary assessment (EMA). Parents (mean age = 35; 95% mothers) of children ages 5-7 years old (n = 61) from six racial/ethnic groups (African American, American Indian, Hispanic, Hmong, Somali, White) participated in this ten-day in-home observation with families. Transient stressors, specifically interpersonal conflicts, had significant within-day effects on engaging in more unhealthful food-related parenting practices the same evening with across-day effects weakening by day three. In contrast, financial transient stressors had stronger across-day effects. Chronic stressors, including stressful life events were not consistently associated with more unhealthful food-related parenting practices. Transient sources of stress were significantly associated with food-related parenting practices in racially/ethnically diverse and immigrant households. Chronic stressors were not consistently associated with food-related parenting practices. Future research and interventions may want to assess for transient sources of stress in

Variety of immune responses to chronic stress in rats male

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Іlona S Polovynko

2016-12-01

Full Text Available Background. Previously we have been carry out integrated quantitative estimation of neuroendocrine and immune responses to chronic restraint stress in male rats. Revealed that the value of canonical discriminant roots rats subjected to chronic stress different not only on the values of intact animals (by definition, but also among themselves. So we set a goal retrospectively divided stressed rats into three homogeneous groups. Material and methods. The experiment is at 50 white male rats. Of these 10 animals not subjected to any influences and 40 within 7 days subjected to moderate stress by daily 30-minute immobilization. The day after the completion of stressing in portion of the blood immunological parameters were determined by tests I and II levels of WHO. The spleen and thymus did smears for counting spleno- and thymocytograms. Results. The method of cluster analysis (k-means clustering formed three groups-clusters. For further analysis selected 18 parameters that members of each cluster differing minimum and maximum are different from members of other clusters (η2=0,73÷0,15; F=49,0÷3,26; p=10-6÷0,05. We stated that in 16 rats from cluster III the deviation 16 parameters in either side of the average norm almost identical and are in an acceptable range of ±0,5σ. Thus, the immune status of 40% of the rats subjected to moderate chronic stress was resistant to its factors. For the immune status of the 15 (37,5% rats cluster II typical moderate inhibition microphage, killer and T-cellular links in combination with a strong activation macrophage link. Poststressory changes in immunity in 9 rats (22,5% from cluster I differ from those in cluster II both qualitatively and quantitatively. In particular, the rats in this cluster were found no deviations from the norm or reaction blast transformation T-cells nor NK-lymphocytes levels. However, other parameters of T-link and microhage link suppressed more and settings macrophage link appeared

Intrinsic and extrinsic apoptotic pathways are involved in rat testis by cold water immersion-induced acute and chronic stress.

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Juárez-Rojas, Adriana Lizbeth; García-Lorenzana, Mario; Aragón-Martínez, Andrés; Gómez-Quiroz, Luis Enrique; Retana-Márquez, María del Socorro

2015-01-01

Testicular apoptosis is activated by stress, but it is not clear which signaling pathway is activated in response to stress. The aim of this study was to investigate whether intrinsic, extrinsic, or both apoptotic signaling pathways are activated by acute and chronic stress. Adult male rats were subjected to cold water immersion-induced stress for 1, 20, 40, and 50 consecutive days. The seminiferous tubules:apoptotic cell ratio was assayed on acute (1 day) and chronic (20, 40, 50 days) stress. Apoptotic markers, including cleaved-caspase 3 and 8, the pro-apoptotic Bax and anti-apoptotic Bcl-2 proteins were also determined after acute and chronic stress induction. Additionally, epididymal sperm quality was evaluated, as well as corticosterone and testosterone levels. An increase in tubule apoptotic cell count percentage after an hour of acute stress and during chronic stress induction was observed. The apoptotic cells rate per tubule increment was only detected one hour after acute stress, but not with chronic stress. Accordingly, there was an increase in Bax, cleaved caspase-8 and caspase-3 pro-apoptotic proteins with a decrease of anti-apoptotic Bcl-2 in both acutely and chronically stressed male testes. In addition, sperm count, viability, as well as total and progressive motility were low in chronically stressed males. Finally, the levels of corticosterone increased whereas testosterone levels decreased in chronically stressed males. Activation of the extrinsic apoptotic pathway was shown by cleaved caspase-8 increase whereas the intrinsic apoptotic pathway activation was determined by the increase of Bax, along with Bcl-2 decrease, making evident a cross-talk between these two pathways with the activation of caspase-3. These results suggest that both acute and chronic stress can potentially activate the intrinsic/extrinsic apoptosis pathways in testes. Chronic stress also reduces the quality of epididymal spermatozoa, possibly due to a decrease in testosterone.

A Growth Curve Analysis of the Course of Dysthymic Disorder: The Effects of Chronic Stress and Moderation by Adverse Parent-Child Relationships and Family History

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Dougherty, Lea R.; Klein, Daniel N.; Davila, Joanne

2004-01-01

Using mixed effects models, the authors examined the effects of chronic stress, adverse parent-child relationships, and family history on the 7.5-year course of dysthymic disorder. Participants included 97 outpatients with early-onset dysthymia who were assessed with semistructured interviews at baseline and 3 additional times at 30-month…

Chronic mitochondrial uncoupling treatment prevents acute cold-induced oxidative stress in birds.

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Stier, Antoine; Massemin, Sylvie; Criscuolo, François

2014-12-01

Endotherms have evolved two major types of thermogenesis that allow them to actively produce heat in response to cold exposure, either through muscular activity (i.e. shivering thermogenesis) or through futile electro-chemical cycles (i.e. non-shivering thermogenesis). Amongst the latter, mitochondrial uncoupling is of key importance because it is suggested to drive heat production at a low cost in terms of oxidative stress. While this has been experimentally shown in mammals, the oxidative stress consequences of cold exposure and mitochondrial uncoupling are clearly less understood in the other class of endotherms, the birds. We compared metabolic and oxidative stress responses of zebra finches chronically treated with or without a chemical mitochondrial uncoupler (2,4-dinitrophenol: DNP), undergoing an acute (24 h) and a chronic (4 weeks) cold exposure (12 °C). We predicted that control birds should present at least a transient elevation of oxidative stress levels in response to cold exposure. This oxidative stress cost should be more pronounced in control birds than in DNP-treated birds, due to their lower basal uncoupling state. Despite similar increase in metabolism, control birds presented elevated levels of DNA oxidative damage in response to acute (but not chronic) cold exposure, while DNP-treated birds did not. Plasma antioxidant capacity decreased overall in response to chronic cold exposure. These results show that acute cold exposure increases oxidative stress in birds. However, uncoupling mitochondrial functioning appears as a putative compensatory mechanism preventing cold-induced oxidative stress. This result confirms previous observations in mice and underlines non-shivering thermogenesis as a putative key mechanism for endotherms in mounting a response to cold at a low oxidative cost.

Effects of stress and MDMA on hippocampal gene expression.

Science.gov (United States)

Weber, Georg F; Johnson, Bethann N; Yamamoto, Bryan K; Gudelsky, Gary A

2014-01-01

MDMA (3,4-methylenedioxymethamphetamine) is a substituted amphetamine and popular drug of abuse. Its mood-enhancing short-term effects may prompt its consumption under stress. Clinical studies indicate that MDMA treatment may mitigate the symptoms of stress disorders such as posttraumatic stress syndrome (PTSD). On the other hand, repeated administration of MDMA results in persistent deficits in markers of serotonergic (5-HT) nerve terminals that have been viewed as indicative of 5-HT neurotoxicity. Exposure to chronic stress has been shown to augment MDMA-induced 5-HT neurotoxicity. Here, we examine the transcriptional responses in the hippocampus to MDMA treatment of control rats and rats exposed to chronic stress. MDMA altered the expression of genes that regulate unfolded protein binding, protein folding, calmodulin-dependent protein kinase activity, and neuropeptide signaling. In stressed rats, the gene expression profile in response to MDMA was altered to affect sensory processing and responses to tissue damage in nerve sheaths. Subsequent treatment with MDMA also markedly altered the genetic responses to stress such that the stress-induced downregulation of genes related to the circadian rhythm was reversed. The data support the view that MDMA-induced transcriptional responses accompany the persistent effects of this drug on neuronal structure/function. In addition, MDMA treatment alters the stress-induced transcriptional signature.

Chronic stress and decreased physical exercise: impact on weight for African American women.

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Moore-Greene, Gracie M; Gross, Susan M; Silver, Kristi D; Perrino, Carrol S

2012-01-01

African American women continue to have the highest prevalence of obesity in the United States and in the state of Maryland they are disproportionately affected by overweight and obesity. There are many contributing factors including chronic stress and the use of health behaviors such as physical exercise that play a role in increased weight for African American women. We examined the relationship of stress to weight and the role of physical exercise in African American paraprofessional women. Cross-sectional study African American paraprofessionals were asked about their perspectives regarding association with chronic stress and physical exercise. The three most salient stressors for the women were finances (33%), work (28%) and family/friends (19%). Ninety percent of the women were overweight or obese. Significant predictors of increased BMI were lack of physical exercise (P = .004) and health compared to others (P = .006). Ethnic discrimination was a form of chronic stress (r = .319) but was not correlated with BMI (r = .095). Decreased physical exercise (P = .02) mediated the relationship between chronic stress and BMI. Findings regarding finance and work stress suggest the need for employers to consider the impact of job strain when implementing employee health programs to decrease stress and improve health. A focus on decreased physical exercise, unhealthy eating habits and misperceptions regarding increased risk for obesity related diseases with health status may be helpful to include in intervention strategies to decrease obesity for this population.

Effect of chronic psychogenic stress on some behavioral and neurochemical characteristics of rats

International Nuclear Information System (INIS)

Danchev, N.D.; Rozhanets, V.V.; Val'dman, A.V.

1986-01-01

This paper studies the behavioral, somatic, and certain neurochemical parameters in rats under conditions of unavoidable chronic stress, according to Hecht et al. in a situation of possible avoidance, with the same total number of aversive stimuli. Specific binding of tritium-flunitrazepam and tritium-dihydroalprenolol was studied. The dissociatin constant and the maximal concentration of ligand-receptor complexes were determined in Scatchard plots by means of an HP-33E computer. The protein concentration in the samples was determined by Peterson's method

Chronic stress accelerates the development of endometriosis in mouse through adrenergic receptor β2.

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Long, Qiqi; Liu, Xishi; Qi, Qiuming; Guo, Sun-Wei

2016-11-01

(a non-specific ADRB agonist), respectively. In all three experiments, the bodyweight and hotplate latency were evaluated before sacrifice 14 days after the induction. In all experimentations, the lesion weight was evaluated and the harvested ectopic endometrial tissue samples were subjected to immunohistochemistry analysis of vascular endothelial growth factor (VEGF), CD31-positive microvessels, proliferating cell nuclear antigen (PCNA), phosphorylated CREB, ADRB1, ADRB2, ADRB3, adrenergic receptor α1 (ADRA1) and ADRA2. Exposure to chronic stress accelerated the development of endometriosis and exacerbated the endometriosis-associated generalized hyperalgesia. This promotional effect is likely to be mediated through the systemic activation of the sympatho-adreno-medullary (SAM) axis, which results in subsequent release of catecholamines. The surging catecholamines may activate ADRB2 and CREB, yielding increased angiogenesis and cellular proliferation in ectopic endometrium in mice with induced endometriosis. In addition, β adrenergic receptor blockade completely abolished the promotional effect of chronic stress, likely through suppression of ADRB2 and CREB activation, thus suppressing angiogenesis and proliferation. Moreover, a non-specific adrenergic β agonist and a specific adrenergic β2 agonist, but not non-specific adrenergic α agonist, acted similarly to chronic stress, accelerating the development of endometriosis and exacerbating the generalized hyperalgesia in mice with pre-existing endometriosis. NA. This study is limited by the use of immunohistochemistry analyses only and the lack of molecular data. The present study provides the experimental evidence that chronic stress can promote the development of endometriosis through the activation of ADRB2. Given ADRB2 is also expressed in human endometriosis and appears to be functional, and in light of recent awareness that adrenergic signaling plays critical roles in tumorigenesis, it is likely that

Effects of low strength pedaling exercise on stress sensitivity and pain threshold

OpenAIRE

坂野, 裕洋

2017-01-01

　This study conducted a comparative assessment of the effects of low intensity lower limb pedaling exercise on the stress sensitivity and pain threshold in healthy subjects and those with chronic stiff neck or lower back pain. The results showed a reduction in pain threshold depending on the applied mechanical stress in both healthy and chronic pain groups. The individuals with chronic pain felt pain more intensely compared to the healthy individuals, and showed a significant reduction in pai...

Enhanced fear recall and emotional arousal in rats recovering from chronic variable stress.

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McGuire, Jennifer; Herman, James P; Horn, Paul S; Sallee, Floyd R; Sah, Renu

2010-11-02

Emergence of posttraumatic-like behaviors following chronic trauma is of interest given the rising prevalence of combat-related posttraumatic stress disorder (PTSD). Stress associated with combat usually involves chronic traumatization, composed of multiple, single episode events occurring in an unpredictable fashion. In this study, we investigated whether rats recovering from repeated trauma in the form of chronic variable stress (CVS) express posttraumatic stress-like behaviors and dysregulated neuroendocrine responses. Cohorts of Long-Evans rats underwent a 7 day CVS paradigm followed by behavioral and neuroendocrine testing during early (16 h post CVS) and delayed (7 day) recovery time points. A fear conditioning-extinction-reminder shock paradigm revealed that CVS induces exaggerated fear recall to reminder shock, suggestive of potentiated fear memory. Rats with CVS experience also expressed a delayed expression of fearful arousal under aversive context, however, social anxiety was not affected during post-CVS recovery. Persistent sensitization of the hypothalamic-pituitary-adrenocorticotropic response to a novel acute stressor was observed in CVS exposed rats. Collectively, our data are consistent with the constellation of symptoms associated with posttraumatic stress syndrome, such as re-experiencing, and arousal to fearful contexts. The CVS-recovery paradigm may be useful to simulate trauma outcomes following chronic traumatization that is often associated with repeated combat stress. Copyright © 2010 Elsevier Inc. All rights reserved.