Associations between HPA axis functioning and level of anxiety in children and adolescents with an anxiety disorder

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Kallen, V. L.; Tulen, J. H. M.; Utens, E. M. W. J.; Treffers, P. D. A.; de Jong, F. H.; Ferdinand, R. F.

2008-01-01

The hypothalamus-pituitary-adrenal (HPA) axis becomes active in response to stress. Hence, increased levels of anxiety in children and adolescents may be associated with changes in HPA-axis functioning. The aim of this study was to test if level of anxiety or specific anxiety disorders were

A sustained hypothalamic-pituitary-adrenal axis response to acute psychosocial stress in irritable bowel syndrome.

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Kennedy, P J; Cryan, J F; Quigley, E M M; Dinan, T G; Clarke, G

2014-10-01

Despite stress being considered a key factor in the pathophysiology of the functional gastrointestinal (GI) disorder irritable bowel syndrome (IBS), there is a paucity of information regarding the ability of IBS patients to respond to acute experimental stress. Insights into the stress response in IBS could open the way to novel therapeutic interventions. To this end, we assessed the response of a range of physiological and psychological parameters to the Trier Social Stress Test (TSST) in IBS. Thirteen female patients with IBS and 15 healthy female age-matched control participants underwent a single exposure to the TSST. Salivary cortisol, salivary C-reactive protein (CRP), skin conductance level (SCL), GI symptoms, mood and self-reported stress were measured pre- and post-exposure to the TSST. The hypothalamic-pituitary-adrenal (HPA) axis response to the TSST was sustained in IBS, as shown by a greater total cortisol output throughout (p = 0.035) and higher cortisol levels measured by an area under the curve with respect to ground (AUCG) analysis (p = 0.044). In IBS patients, GI symptoms increased significantly during the recovery period following exposure to the TSST (p = 0.045). Salivary CRP and SCL activity showed significant changes in relation to stress but with no differential effect between experimental groups. Patients with IBS exhibit sustained HPA axis activity, and an increase in problematic GI symptoms in response to acute experimental psychosocial stress. These data pave the way for future interventional studies aimed at identifying novel therapeutic approaches to modulate the HPA axis and GI symptom response to acute psychosocial stress in IBS.

Regulation of the corticosteroid signalling system in rainbow trout HPI axis during confinement stress.

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Kiilerich, Pia; Servili, Arianna; Péron, Sandrine; Valotaire, Claudiane; Goardon, Lionel; Leguen, Isabelle; Prunet, Patrick

2018-03-01

This study aims to shed light on corticosteroid regulation of stress in teleost fish with focus on the corticosteroid signalling system. The role of the mineralocorticoid-like hormone 11-deoxycorticosterone (DOC) in fish is still enigmatic, as is the function of the mineralocorticoid receptor, MR. Low plasma DOC levels and ubiquitous tissue distribution of MR question the physiological relevance of the mineralocorticoid-axis. Furthermore, the particular purpose of each of the three corticosteroid receptors in fish, the glucocorticoid receptors, GR1 and GR2, and the MR, is still largely unknown. Therefore we investigate the regulation of cortisol and DOC in plasma and mRNA levels of MR, GR1 and GR2 in the HPI-axis tissues (hypothalamus, pituitary and interrenal gland) during a detailed confinement stress time-course. Here we show a sustained up-regulation of plasma DOC levels during a confinement stress time-course. However, the low DOC levels compared to cortisol measured in the plasma do not favour an activity of DOC through MR receptors. Furthermore, we show differential contribution of the CRs in regulation and control of HPI axis activity following confinement stress. Judged by the variation of mRNA levels negative feedback regulation of cortisol release occurs on the level of the pituitary via MR and on the level of the interrenal gland via GR2. Finally, asa significant effect of confinement stress on CR expressions was observed in the pituitary gland, we completed this experiment by demonstrating that corticosteroid receptors (GR1, GR2 and MR) are co-expressed in the ACTH cells located in the adenohypophysis. Overall, these data suggest the involvement of these receptors in the regulation of the HPI axis activity by cortisol. Copyright © 2017 Elsevier Inc. All rights reserved.

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

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

2007-01-01

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

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

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Whitaker, Annie M; Gilpin, Nicholas W

2015-08-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

[Corticotropic axis and chronic stress in abdominal obesity and metabolic syndrome].

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Boullu-Ciocca, S; Verger, P; Bocquier, A; Oliver, C

2005-12-03

Several indicators of corticotropic axis hyperactivity have been observed in common abdominal obesity, which is clinically similar to the obesity found in Cushing's syndrome. Corticotropic axis hyperactivity may be involved in the development and metabolic and cardiovascular complications of abdominal obesity. Several mechanisms may be responsible for this hormonal dysregulation: genetic, lifestyle, and nutritional factors, and chronic stress. We note the necessity of methodologically-impeccable clinical studies for an objective evaluation of the role of stress in obesity.

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

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Li-Juan Zhu

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

Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress

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Ryan, Karen K; Mul, Joram D; Clemmensen, Christoffer

2014-01-01

function. These results support the hypothesis that endogenous MC4R signaling contributes to the HPA axis response to stress. Because MC4R plays a critical role in the regulation of energy balance, the present work suggests that it may also serve as an important communication link between brain metabolic...... in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function. In this study, adult male rats were......The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated...

Early life stress, HPA axis adaptation and mechanisms contributing to later health outcomes

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Jayanthi eManiam

2014-05-01

Full Text Available Stress activates the hypothalamic-pituitary-adrenal (HPA axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early life stress can impact on later health but less is known about how early life stress impairs HPA axis activity, contributing to maladaptation of the stress response system. Early life stress exposure (either prenatally or in the early postnatal period can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical and experimental studies have demonstrated that early life stress produces long-term hyper responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviours. Recently, evidence has emerged on early life stress induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1. We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early life stress induced maladaptation of the HPA axis, and its subsequent effects on energy utilisation and expenditure. The effects of positive later environments as a means of ameliorating early life stress induced health deficits, and proposed mechanisms underpinning the interaction between early life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early life stress and later health outcomes will also

Daily family stress and HPA axis functioning during adolescence: The moderating role of sleep

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Chiang, Jessica J.; Tsai, Kim M.; Park, Heejung; Bower, Julienne E.; Almeida, David M.; Dahl, Ronald E.; Irwin, Michael R.; Seeman, Teresa E.; Fuligni, Andrew J.

2017-01-01

The present study examined the moderating role of sleep in the association between family demands and conflict and hypothalamic-pituitary-adrenal (HPA) axis functioning in a sample of ethnically diverse adolescents (n = 316). Adolescents completed daily diary reports of family demands and conflict for 15 days, and wore actigraph watches during the first 8 nights to assess sleep. Participants also provided five saliva samples for 3 consecutive days to assess diurnal cortisol rhythms. Regression analyses indicated that sleep latency and efficiency moderated the link between family demands and the cortisol awakening response. Specifically, family demands were related to a smaller cortisol awakening response only among adolescents with longer sleep latency and lower sleep efficiency. These results suggest that certain aspects of HPA axis functioning may be sensitive to family demands primarily in the context of longer sleep latency and lower sleep efficiency. PMID:27235639

The BDNF Val66Met polymorphism affects HPA-axis reactivity to acute stress.

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Alexander, Nina; Osinsky, Roman; Schmitz, Anja; Mueller, Eva; Kuepper, Yvonne; Hennig, Juergen

2010-07-01

Growing evidence suggests that individual differences in HPA-axis reactivity to psychosocial stress are partly due to heritable influences. However, knowledge about the role of specific genetic variants remains very limited to date. Since brain-derived neurotrophic factor (BDNF) not only exhibits neurotrophic actions but is also involved in the regulation of hypothalamic neuropeptides, we investigated the role of a common functional polymorphism within the BDNF gene (BDNF Val66Met) in the context of endocrine and cardiovascular stress reactivity. Healthy male adults (N=100) were genotyped and exposed to a standardized laboratory stress task (Public Speaking). Saliva cortisol and self-reported mood levels were obtained at 6 time points prior to the stressor and during an extended recovery period. Furthermore, heart rate reactivity as an indicator of sympathetic activation was monitored continuously during the experimental procedure. We report a small, but significant effect of the BDNF Val66Met polymorphism on stress reactivity. More precisely, carriers of the met-allele showed a significantly attenuated HPA-axis and cardiovascular reactivity to the psychosocial stressor compared to subjects with the val/val genotype. Furthermore, the diminished physiological response in met-allele carriers was also attended by significantly lower self-reported ratings of perceived stress and nervousness. Our findings of a diminished endocrine and cardiovascular stress response in healthy male adults is consistent with a previously published study and adds further evidence for a crucial role of the BDNF Val66Met polymorphism in the modulation of stress reactivity. Copyright 2010. Published by Elsevier Ltd.

Early-Life Stress, HPA Axis Adaptation, and Mechanisms Contributing to Later Health Outcomes

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Maniam, Jayanthi; Antoniadis, Christopher; Morris, Margaret J.

2014-01-01

Stress activates the hypothalamic–pituitary–adrenal (HPA) axis, which then modulates the degree of adaptation and response to a later stressor. It is known that early-life stress can impact on later health but less is known about how early-life stress impairs HPA axis activity, contributing to maladaptation of the stress–response system. Early-life stress exposure (either prenatally or in the early postnatal period) can impact developmental pathways resulting in lasting structural and regulatory changes that predispose to adulthood disease. Epidemiological, clinical, and experimental studies have demonstrated that early-life stress produces long term hyper-responsiveness to stress with exaggerated circulating glucocorticoids, and enhanced anxiety and depression-like behaviors. Recently, evidence has emerged on early-life stress-induced metabolic derangements, for example hyperinsulinemia and altered insulin sensitivity on exposure to a high energy diet later in life. This draws our attention to the contribution of later environment to disease vulnerability. Early-life stress can alter the expression of genes in peripheral tissues, such as the glucocorticoid receptor and 11-beta hydroxysteroid dehydrogenase (11β-HSD1). We propose that interactions between altered HPA axis activity and liver 11β-HSD1 modulates both tissue and circulating glucocorticoid availability, with adverse metabolic consequences. This review discusses the potential mechanisms underlying early-life stress-induced maladaptation of the HPA axis, and its subsequent effects on energy utilization and expenditure. The effects of positive later environments as a means of ameliorating early-life stress-induced health deficits, and proposed mechanisms underpinning the interaction between early-life stress and subsequent detrimental environmental exposures on metabolic risk will be outlined. Limitations in current methodology linking early-life stress and later health outcomes will also be

Stress and the Microbiota-Gut-Brain Axis in Visceral Pain: Relevance to Irritable Bowel Syndrome.

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Moloney, Rachel D; Johnson, Anthony C; O'Mahony, Siobhain M; Dinan, Timothy G; Greenwood-Van Meerveld, Beverley; Cryan, John F

2016-02-01

Visceral pain is a global term used to describe pain originating from the internal organs of the body, which affects a significant proportion of the population and is a common feature of functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome (IBS). While IBS is multifactorial, with no single etiology to completely explain the disorder, many patients also experience comorbid behavioral disorders, such as anxiety or depression; thus, IBS is described as a disorder of the gut-brain axis. Stress is implicated in the development and exacerbation of visceral pain disorders. Chronic stress can modify central pain circuitry, as well as change motility and permeability throughout the gastrointestinal (GI) tract. More recently, the role of the gut microbiota in the bidirectional communication along the gut-brain axis, and subsequent changes in behavior, has emerged. Thus, stress and the gut microbiota can interact through complementary or opposing factors to influence visceral nociceptive behaviors. This review will highlight the evidence by which stress and the gut microbiota interact in the regulation of visceral nociception. We will focus on the influence of stress on the microbiota and the mechanisms by which microbiota can affect the stress response and behavioral outcomes with an emphasis on visceral pain. © 2015 John Wiley & Sons Ltd.

Stress reactivity in childhood functional abdominal pain or irritable bowel syndrome.

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Gulewitsch, M D; Weimer, K; Enck, P; Schwille-Kiuntke, J; Hautzinger, M; Schlarb, A A

2017-01-01

Frequent abdominal pain (AP) in childhood has been shown to be associated with elevated experience of stress and with deficits in stress coping, but psychophysiological stress reactivity has been studied rarely. We examined whether children with frequent AP show altered reactions of the parasympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis during and following an afternoon laboratory social stress task in comparison to healthy children and children with anxiety disorders. Twenty-four children with frequent AP (18 with functional AP and six with irritable bowel syndrome; M = 9.9 years), and 24 healthy controls underwent stressful free speech and arithmetic tasks. Twelve children with anxiety disorders served as second comparison sample. Groups were compared regarding parasympathetic reaction and saliva cortisol concentration. We found no differences in parasympathetic withdrawal between the groups. Concerning the HPA axis, we detected an attenuated cortisol reactivity in children with AP compared to both other groups. This study provides preliminary evidence that childhood AP is not associated with altered parasympathetic withdrawal during stress. It seems to be related to a down-regulated reactivity of the HPA axis. This pattern was ascertained in comparison to healthy children and also in comparison to children with anxiety disorders. Childhood abdominal pain could be related to down-regulated HPA axis reactivity to stress but not to altered parasympathetic reaction. Children with abdominal pain and children with anxiety disorders exhibit a divergent stress-related HPA axis reaction. © 2016 European Pain Federation - EFIC®.

Rev1 contributes to proper mitochondrial function via the PARP-NAD(+)-SIRT1-PGC1 alpha axis

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Fakouri, Nima Borhan; Durhuus, Jon Ambaek; Regnell, Christine Elisabeth

2017-01-01

(ADP) ribose polymerase 1 (PARP1) activity, low endogenous NAD+, low expression of SIRT1 and PGC1α and low adenosine monophosphate (AMP)-activated kinase (AMPK) activity. We conclude that replication stress via Rev1-deficiency contributes to metabolic stress caused by compromized mitochondrial function via...... the PARP-NAD+-SIRT1-PGC1α axis....

Exercise-induced stress behavior, gut-microbiota-brain axis and diet: a systematic review for athletes.

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Clark, Allison; Mach, Núria

2016-01-01

Fatigue, mood disturbances, under performance and gastrointestinal distress are common among athletes during training and competition. The psychosocial and physical demands during intense exercise can initiate a stress response activating the sympathetic-adrenomedullary and hypothalamus-pituitary-adrenal (HPA) axes, resulting in the release of stress and catabolic hormones, inflammatory cytokines and microbial molecules. The gut is home to trillions of microorganisms that have fundamental roles in many aspects of human biology, including metabolism, endocrine, neuronal and immune function. The gut microbiome and its influence on host behavior, intestinal barrier and immune function are believed to be a critical aspect of the brain-gut axis. Recent evidence in murine models shows that there is a high correlation between physical and emotional stress during exercise and changes in gastrointestinal microbiota composition. For instance, induced exercise-stress decreased cecal levels of Turicibacter spp and increased Ruminococcus gnavus, which have well defined roles in intestinal mucus degradation and immune function. Diet is known to dramatically modulate the composition of the gut microbiota. Due to the considerable complexity of stress responses in elite athletes (from leaky gut to increased catabolism and depression), defining standard diet regimes is difficult. However, some preliminary experimental data obtained from studies using probiotics and prebiotics studies show some interesting results, indicating that the microbiota acts like an endocrine organ (e.g. secreting serotonin, dopamine or other neurotransmitters) and may control the HPA axis in athletes. What is troubling is that dietary recommendations for elite athletes are primarily based on a low consumption of plant polysaccharides, which is associated with reduced microbiota diversity and functionality (e.g. less synthesis of byproducts such as short chain fatty acids and neurotransmitters). As more

Stress axis regulation during social ascension in a group-living cichlid fish.

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Culbert, Brett M; Gilmour, Kathleen M; Balshine, Sigal

2018-06-19

Animals living in groups often form social hierarchies, with characteristic behaviours and physiologies associated with rank. However, when social opportunities arise and a subordinate ascends into a dominant position, quick adjustments are necessary to secure this position. Such periods of social transition are typically associated with elevated glucocorticoid production, but the precise regulation of the stress axis during these occasions is not well understood. Using the group-living cichlid, Neolamprologus pulcher, the effects of social ascension on the stress axis were assessed. Ascenders rapidly filled experimentally created vacancies, adopting a dominant behavioural phenotype within 72 h-elevating aggression, activity, and workload, while receiving high rates of affiliative behaviours from their group members. Despite assuming behavioural dominance within their groups, ascenders displayed higher cortisol levels than dominants three days post-ascension. Additionally, compared to subordinates, ascenders had increased transcript abundance of steroidogenic acute regulatory protein (star) and cytochrome p450 side-chain cleavage enzyme (p450scc) in the head kidney, indicating activation of the stress axis. Cortisol levels were lowest in ascenders that displayed low rates of aggression, potentially reflecting the reestablishment of social stability in these groups. Increased transcript abundance of both glucocorticoid receptors (gr1 and gr2) in the brain's preoptic area (POA) of ascenders compared to dominants suggested an enhanced capacity for cortisol regulation via negative feedback. Our results reveal a regulatory cascade of behavioural and physiological interactions and highlight the importance of investigating the underlying mechanisms regulating the stress axis. Copyright © 2018. Published by Elsevier Inc.

The Hypothalamic-Pituitary-Adrenal Axis, Obesity, and Chronic Stress Exposure: Sleep and the HPA Axis in Obesity

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Lucassen, Eliane A.; Cizza, Giovanni

2012-01-01

Obesity, exposure to stress and inadequate sleep are prevalent phenomena in modern society. In this review we focus on their relationships and critically evaluate causality. In obese individuals, one of the main stress systems, the hypothalamic-pituitary-adrenal axis, is altered, and concentrations of cortisol are elevated in adipose tissue due to elevated local activity of 11β-hydroxysteroid dehydrogenase (HSD) type 1. Short sleep and decreased sleep quality are also associated with obesity....

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

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Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

2017-04-01

Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

FLEXURAL STRESS ANALYSIS OF RIGID PAVEMENTS USING AXI-SYMMETRIC AND PLANE STRAIN FEM

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V.A. Sawant

2017-11-01

Full Text Available The design of pavement involves a study of soils and paving materials, their response under load for different climatic conditions. In the present study, an attempt has been made to compare stresses predicted using two finite element analyses. First analysis is based on the twodimensional plane strain assumption where as in second approach axi-symmetric condition is assumed to consider three-dimensional behavior of rigid pavement. The results are compared with flexural stresses obtained from conventional Portland Cement Association method. The computed flexural stresses obtained from axi-symmetric condition are found to be in close agreement with PCA method. Results of plane strain analysis show a fair agreement after application of an appropriate multiplication factor

Hypothalamic-pituitary-adrenal axis response to acute psychosocial stress: Effects of biological sex and circulating sex hormones.

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Stephens, Mary Ann C; Mahon, Pamela B; McCaul, Mary E; Wand, Gary S

2016-04-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis influences the risk for developing stress-related disorders. Sex-dependent differences in the HPA axis stress response are believed to contribute to the different prevalence rates of stress-related disorders found in men and women. However, studies examining the HPA axis stress response have shown mixed support for sex differences, and the role of endogenous sex hormones on HPA axis response has not been adequately examined in humans. This study utilized the largest sample size to date to analyze the effects of biological sex and sex hormones on HPA axis social stress responses. Healthy, 18- to 30- year-old community volunteers (N=282) completed the Trier Social Stress Test (TSST), a widely used and well-validated stress-induction laboratory procedure. All women (n=135) were tested during the follicular phase of their menstrual cycle (when progesterone levels are most similar to men). Adrenocorticotropic hormone (ACTH) and cortisol measures were collected at multiple points throughout pre- and post-TSST. Testosterone and progesterone (in men) and progesterone and estradiol (in women) were determined pre-TSST. Following the TSST, men had greater ACTH and cortisol levels than women. Men had steeper baseline-to-peak and peak-to-end ACTH and cortisol response slopes than women; there was a trend for more cortisol responders among men than women. Testosterone negatively correlated with salivary cortisol response in men, while progesterone negatively correlated with ACTH and cortisol responses in women. These data confirm that men show more robust activation of the HPA axis response to the TSST than do women in the follicular phase of the menstrual cycle. Testosterone results suggest an inhibitory effect on HPA axis reactivity in men. Progesterone results suggest an inhibitory effect on HPA axis reactivity in women. Future work is needed to explain why men mount a greater ACTH and cortisol response to the

Age-related differences in stress responsiveness of the hypothalamic-pituitary-adrenal axis of nonhuman primates with various types of adaptive behavior.

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Goncharova, Nadezhda D; Oganyan, Tamara E

2018-03-01

Aging is characterized by disturbances in the functioning of the hypothalamic-pituitary-adrenal (HPA) axis, associated with disturbances in the adaptation processes and increase of the probability of the onset of post-stress syndrome. However, the individual features of age-related disorders stress reactivity of HPA axis have not been studied. The purpose was to study individual characteristics of the HPA axis responsiveness to acute psycho-emotional stress exposure (restraint, ASE) at different age periods on the model of the young adult and old physically healthy female rhesus monkeys that differ in their behavioral responses to stress, i.e., with depression-like and anxiety-like behavior (DAB) on the one hand and healthy standard (control) adaptive behavior (SB) on the other hand. No significant intergroup differences were observed in HPA axis responses to ASE in young animals. During aging the monkeys with SB showed reduced ACTH response to the ASE, whereas the monkeys with DAB demonstrated its increase. The old animals with DAB in response to ASE demonstrated the most pronounced HPA axis disorders, such as the highest levels of corticotrophin (ACTH), the lowest levels of dehydroepiandrosterone sulfate (DHEAS), reduced cortisol (F) levels and the highest values of the F/DHEAS molar ratio. The ratio F/DHEAS positively correlates with the malondialdehyde concentration in erythrocytes that is considered as the biomarker of oxidative stress. Thus, these data allow us to consider the old monkeys with DAB as individuals with higher vulnerability to the adverse effects of ASE. In addition, depression-like and anxiety-like behavior of aged primates under mild/moderate stress along with reduced DHEAS plasma concentration and increased values of F/DHEAS ratio can be used to identify individuals with increased vulnerability to ASE and accelerated aging. Copyright © 2017 Elsevier Inc. All rights reserved.

Chronic stress and pituitary-adrenal function in female pigs

NARCIS (Netherlands)

Janssens, C.J.J.G.

1994-01-01

Introduction

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

Adversity-driven changes in hypothalamic-pituitary-adrenal axis functioning during adolescence

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

2017-01-01

The hypothalamic-pituitary-adrenal (HPA) axis has been proposed to be a key mechanism underlying the link between adversity and mental health, but longitudinal studies on adversity and HPA-axis functioning are scarce. Here, we studied adversity-driven changes in HPA-axis functioning during

Brain angiotensin-(1-7)/Mas axis: A new target to reduce the cardiovascular risk to emotional stress.

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Fontes, Marco Antônio Peliky; Martins Lima, Augusto; Santos, Robson Augusto Souza dos

2016-04-01

Emotional stress is now considered a risk factor for several diseases including cardiac arrhythmias and hypertension. It is well known that the activation of neuroendocrine and autonomic mechanisms features the response to emotional stress. However, its link to cardiovascular diseases and the regulatory mechanisms involved remain to be further comprehended. The renin-angiotensin system (RAS) plays an important role in homeostasis on all body systems. Specifically in the brain, the RAS regulates a number of physiological aspects. Recent data indicate that the activation of angiotensin-converting enzyme/angiotensin II/AT1 receptor axis facilitates the emotional stress responses. On the other hand, growing evidence indicates that its counterregulatory axis, the angiotensin-converting enzyme 2 (ACE2)/(Ang)iotensin-(1-7)/Mas axis, reduces anxiety and attenuates the physiological responses to emotional stress. The present review focuses on angiotensin-(1-7)/Mas axis as a promising target to attenuate the physiological response to emotional stress reducing the risk of cardiovascular diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Prenatal stress modifies behavior and hypothalamic-pituitary-adrenal function in female guinea pig offspring: effects of timing of prenatal stress and stage of reproductive cycle.

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Kapoor, Amita; Matthews, Stephen G

2008-12-01

Prenatal stress is associated with altered behavior and hypothalamic-pituitary-adrenal (HPA) axis function postnatally. Recent studies suggest that these outcomes are dependent on the timing of the prenatal stress. The majority of these studies have been carried out in male offspring. We hypothesized that a short period of prenatal stress would result in female offspring that exhibit differences in open-field behavior and HPA axis activity, but the outcome would depend on the timing of the prenatal stress and the stage of the reproductive cycle. Pregnant guinea pigs were exposed to a strobe light during the fetal brain growth spurt [gestational d 50-52 (PS50)] or during the period of rapid brain myelination [gestational d 60-62 (PS60)]. Open-field activity was assessed in juvenile and adult female offspring. HPA axis function was tested in adult offspring. All tests in adulthood were carried out during the estrous and luteal phases of the reproductive cycle to determine the effect of stage on HPA axis programming. Tissues were collected upon completion of the study for analysis by in situ hybridization. PS60 offspring exhibited decreased activity in an open field during the estrous phase of the reproductive cycle compared with control offspring. Both PS50 and PS60 offspring exhibited a lower salivary cortisol response to a stressor, only during the estrous phase. Consistent with the behavioral and endocrine data, PS60 females exhibited lower plasma estradiol levels, reduced ovary weight, and increased glucocorticoid receptor mRNA in the paraventricular nucleus. In conclusion, we have demonstrated that there are effects of prenatal stress on behavior and HPA axis functioning in female offspring but that the outcomes are dependent on the timing of the prenatal stress together with the status of the reproductive cycle.

The joint power of sex and stress to modulate brain-gut-microbiota axis and intestinal barrier homeostasis: implications for irritable bowel syndrome.

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Pigrau, M; Rodiño-Janeiro, B K; Casado-Bedmar, M; Lobo, B; Vicario, M; Santos, J; Alonso-Cotoner, C

2016-04-01

Intestinal homeostasis is a dynamic process that takes place at the interface between the lumen and the mucosa of the gastrointestinal tract, where a constant scrutiny for antigens and toxins derived from food and microorganisms is carried out by the vast gut-associated immune system. Intestinal homeostasis is preserved by the ability of the mucus layer and the mucosal barrier to keep the passage of small-sized and antigenic molecules across the epithelium highly selective. When combined and preserved, immune surveillance and barrier's selective permeability, the host capacity of preventing the development of intestinal inflammation is optimized, and viceversa. In addition, the brain-gut-microbiome axis, a multidirectional communication system that integrates distant and local regulatory networks through neural, immunological, metabolic, and hormonal signaling pathways, also regulates intestinal function. Dysfunction of the brain-gut-microbiome axis may induce the loss of gut mucosal homeostasis, leading to uncontrolled permeation of toxins and immunogenic particles, increasing the risk of appearance of intestinal inflammation, mucosal damage, and gut disorders. Irritable bowel syndrome is prevalent stress-sensitive gastrointestinal disorder that shows a female predominance. Interestingly, the role of stress, sex and gonadal hormones in the regulation of intestinal mucosal and the brain-gut-microbiome axis functioning is being increasingly recognized. We aim to critically review the evidence linking sex, and stress to intestinal barrier and brain-gut-microbiome axis dysfunction and the implications for irritable bowel syndrome. © 2015 John Wiley & Sons Ltd.

Adolescent Survivors of Hurricane Katrina: A Pilot Study of Hypothalamic-Pituitary-Adrenal Axis Functioning

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Pfefferbaum, Betty; Tucker, Phebe; Nitiéma, Pascal

2015-01-01

Background: The hypothalamic-pituitary-adrenal (HPA) axis constitutes an important biological component of the stress response commonly studied through the measurement of cortisol. Limited research has examined HPA axis dysregulation in youth exposed to disasters. Objective: This study examined HPA axis activation in adolescent Hurricane Katrina…

The microbiota-gut-brain axis as a key regulator of neural function and the stress response: Implications for human and animal health.

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Wiley, N C; Dinan, T G; Ross, R P; Stanton, C; Clarke, G; Cryan, J F

2017-07-01

The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression. Therefore, much research effort in recent years has focused on understanding the potential of targeting the intestinal microbiota to prevent and treat such disorders. This review aims to explore the influence of the gut microbiota on host neural function and behavior, particularly those of relevance to stress-related disorders. The involvement of microbiota in diverse neural functions such as myelination, microglia function, neuronal morphology, and blood-brain barrier integrity across the life span, from early life to adolescence to old age, will also be discussed. Nurturing an optimal gut microbiome may also prove beneficial in animal science as a means to manage stressful situations and to increase productivity of farm animals. The implications of these observations are manifold, and researchers are hopeful that this promising body of preclinical work can be successfully translated to the clinic and beyond.

A ghrelin-growth hormone axis drives stress-induced vulnerability to enhanced fear.

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Meyer, R M; Burgos-Robles, A; Liu, E; Correia, S S; Goosens, K A

2014-12-01

Hormones in the hypothalamus-pituitary-adrenal (HPA) axis mediate many of the bodily responses to stressors, yet there is no clear relationship between the levels of these hormones and stress-associated mental illnesses such as posttraumatic stress disorder (PTSD). Therefore, other hormones are likely to be involved in this effect of stress. Here we used a rodent model of PTSD in which rats repeatedly exposed to a stressor display heightened fear learning following auditory Pavlovian fear conditioning. Our results show that stress-related increases in circulating ghrelin, a peptide hormone, are necessary and sufficient for stress-associated vulnerability to exacerbated fear learning and these actions of ghrelin occur in the amygdala. Importantly, these actions are also independent of the classic HPA stress axis. Repeated systemic administration of a ghrelin receptor agonist enhanced fear memory but did not increase either corticotropin-releasing factor (CRF) or corticosterone. Repeated intraamygdala infusion of a ghrelin receptor agonist produced a similar enhancement of fear memory. Ghrelin receptor antagonism during repeated stress abolished stress-related enhancement of fear memory without blunting stress-induced corticosterone release. We also examined links between ghrelin and growth hormone (GH), a major downstream effector of the ghrelin receptor. GH protein was upregulated in the amygdala following chronic stress, and its release from amygdala neurons was enhanced by ghrelin receptor stimulation. Virus-mediated overexpression of GH in the amygdala was also sufficient to increase fear. Finally, virus-mediated overexpression of a GH receptor antagonist was sufficient to block the fear-enhancing effects of repeated ghrelin receptor stimulation. Thus, ghrelin requires GH in the amygdala to exert fear-enhancing effects. These results suggest that ghrelin mediates a novel branch of the stress response and highlight a previously unrecognized role for ghrelin and

Beyond the HPA axis: progesterone-derived neuroactive steroids in human stress and emotion

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Michelle eWirth

2011-08-01

Full Text Available Stress and social isolation are well-known risk factors for psychopathology. However, more research is needed as to the physiological mechanisms by which social support buffers the impacts of stress. Research in animal models suggests important roles for progesterone (P and its product, the neuroactive steroid allopregnanolone (ALLO, in stress and psychopathology. These hormones are produced in brain and periphery during stress in rodents, and down-regulate anxiety behavior and HPA axis activity. Human clinical populations, including depressed patients, have alterations in ALLO levels, but it is unclear whether these basal hormone level differences have clinical import. To begin to address this question, this review examines the role of P and ALLO in stress physiology, and the impact of these hormones on mood, in healthy humans. Evidence largely supports that P and ALLO increase during stress in humans. However, P/ALLO administration appears to cause only mild effects on mood and subjective anxiety, while exerting effects consistent with GABA receptor modulation. Additionally, P is linked to motivation for affiliation / social contact; P (and ALLO release may be especially responsive to social rejection. These observations lead to the novel hypothesis that stress-related P/ALLO production functions not only to down-regulate stress and anxiety, but also to promote social contact as a long-term coping strategy. Malfunctioning of the P/ALLO system could therefore underlie depression partly by decreasing propensity to affiliate with others.

Interactions Between Stress and Sex in Microbial Responses Within the Microbiota-Gut-Brain Axis in a Mouse Model.

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Tsilimigras, Matthew C B; Gharaibeh, Raad Z; Sioda, Michael; Gray, Laura; Fodor, Anthony A; Lyte, Mark

2018-05-01

Animal models are frequently used to examine stress response, but experiments seldom include females. The connection between the microbiota-gut-brain axis and behavioral stress response is investigated here using a mixed-sex mouse cohort. CF-1 mice underwent alternating days of restraint and forced swim for 19 days (male n = 8, female n = 8) with matching numbers of control animals at which point the 16S rRNA genes of gut microbiota were sequenced. Mixed linear models accounting for stress status and sex with individuals nested in cage to control for cage effects evaluated these data. Murine behaviors in elevated plus-maze, open-field, and light/dark box were investigated. Community-level associations with sex, stress, and their interaction were significant. Males had higher microbial diversity than females (p = .025). Of the 638 operational taxonomic units detected in at least 25% of samples, 94 operational taxonomic units were significant: 31 (stress), 61 (sex), and 34 (sex-stress interaction). Twenty of the 39 behavioral measures were significant for stress, 3 for sex, and 6 for sex-stress. However, no significant associations between behavioral measures and specific microbes were detected. These data suggest sex influences stress response and the microbiota-gut-brain axis and that studies of behavior and the microbiome therefore benefit from consideration of how sex differences drive behavior and microbial community structure. Host stress resilience and absence of associations between stress-induced behaviors with specific microbes suggests that hypothalamic-pituitary-adrenal axis activation represents a threshold for microbial influence on host behavior. Future studies are needed in examining the intersection of sex, stress response, and the microbiota-gut-brain axis.

Association between Mastication, the Hippocampus, and the HPA Axis: A Comprehensive Review.

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Azuma, Kagaku; Zhou, Qian; Niwa, Masami; Kubo, Kin-Ya

2017-08-03

Mastication is mainly involved in food intake and nutrient digestion with the aid of teeth. Mastication is also important for preserving and promoting general health, including hippocampus-dependent cognition. Both animal and human studies indicate that mastication influences hippocampal functions through the end product of the hypothalamic-pituitary-adrenal (HPA) axis, glucocorticoid (GC). Epidemiologic studies suggest that masticatory dysfunction in aged individuals, such as that resulting from tooth loss and periodontitis, acting as a source of chronic stress, activates the HPA axis, leading to increases in circulating GCs and eventually inducing various physical and psychological diseases, such as cognitive impairment, cardiovascular disorders, and osteoporosis. Recent studies demonstrated that masticatory stimulation or chewing during stressful conditions suppresses the hyperactivity of the HPA axis via GCs and GC receptors within the hippocampus, and ameliorates chronic stress-induced hippocampus-dependent cognitive deficits. Here, we provide a comprehensive overview of current research regarding the association between mastication, the hippocampus, and HPA axis activity. We also discuss several potential molecular mechanisms involved in the interactions between mastication, hippocampal function, and HPA axis activity.

Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

OpenAIRE

Tessa K Solomon-Lane; Erica J Crespi; Erica J Crespi; Matthew Scott Grober; Matthew Scott Grober

2013-01-01

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has ...

Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change

OpenAIRE

Solomon-Lane, Tessa K.; Crespi, Erica J.; Grober, Matthew S.

2013-01-01

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has be...

Influence of early life stress on later hypothalamic-pituitary-adrenal axis functioning and its covariation with mental health symptoms: a study of the allostatic process from childhood into adolescence.

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Essex, Marilyn J; Shirtcliff, Elizabeth A; Burk, Linnea R; Ruttle, Paula L; Klein, Marjorie H; Slattery, Marcia J; Kalin, Ned H; Armstrong, Jeffrey M

2011-11-01

The hypothalamic-pituitary-adrenal (HPA) axis is a primary mechanism in the allostatic process through which early life stress (ELS) contributes to disease. Studies of the influence of ELS on children's HPA axis functioning have yielded inconsistent findings. To address this issue, the present study considers multiple types of ELS (maternal depression, paternal depression, and family expressed anger), mental health symptoms, and two components of HPA functioning (traitlike and epoch-specific activity) in a long-term prospective community study of 357 children. ELS was assessed during the infancy and preschool periods; mental health symptoms and cortisol were assessed at child ages 9, 11, 13, and 15 years. A three-level hierarchical linear model addressed questions regarding the influences of ELS on HPA functioning and its covariation with mental health symptoms. ELS influenced traitlike cortisol level and slope, with both hyper- and hypoarousal evident depending on type of ELS. Further, type(s) of ELS influenced covariation of epoch-specific HPA functioning and mental health symptoms, with a tighter coupling of HPA alterations with symptom severity among children exposed previously to ELS. Results highlight the importance of examining multiple types of ELS and dynamic HPA functioning in order to capture the allostatic process unfolding across the transition into adolescence.

The impact of reproduction on the stress axis of free-living male northern red backed voles (Myodes rutilus).

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Fletcher, Quinn E; Dantzer, Ben; Boonstra, Rudy

2015-12-01

Activation of the hypothalamic-pituitary-adrenal (HPA) axis culminates in the release of glucocorticoids (henceforth CORT), which have wide-reaching physiological effects. Three hypotheses potentially explain seasonal variation in CORT. The enabling hypothesis predicts that reproductive season CORT exceeds post-reproductive season CORT because CORT enables reproductive investment. The inhibitory hypothesis predicts the opposite because CORT can negatively affect reproductive function. The costs of reproduction hypothesis predicts that HPA axis condition declines over and following the reproductive season. We tested these hypotheses in wild male red-backed voles (Myodes rutilus) during the reproductive and post-reproductive seasons. We quantified CORT levels in response to restraint stress tests consisting of three blood samples (initial, stress-induced, and recovery). Mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA levels in the brain were also quantified over the reproductive season. Total CORT (tCORT) in the initial and stress-induced samples were greater in the post-reproductive than in the reproductive season, which supported the inhibitory hypothesis. Conversely, free CORT (fCORT) did not differ between the reproductive and post-reproductive seasons, which was counter to both the enabling and inhibitory hypotheses. Evidence for HPA axis condition decline in CORT as well as GR and MR mRNA over the reproductive season (i.e. costs of reproduction hypothesis) was mixed. Moreover, all of the parameters that showed signs of declining condition over the reproductive season did not also show signs of declining condition over the post-reproductive season suggesting that the costs resulting from reproductive investment had subsided. In conclusion, our results suggest that different aspects of the HPA axis respond differently to seasonal changes and reproductive investment. Copyright © 2015 Elsevier Inc. All rights reserved.

Ultraviolet (UV and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE Cell Apoptosis

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Jin Yao

2013-05-01

Full Text Available Ultraviolet (UV radiation and reactive oxygen species (ROS impair the physiological functions of retinal pigment epithelium (RPE cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD. The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER stress-AMP activated protein kinase (AMPK signaling axis in UV and hydrogen peroxide (H2O2-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal, ceramide production (fumonisin B1 and AMPK activation (compound C suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis.

Association of HPA axis-related genetic variation with stress reactivity and aggressive behaviour in pigs

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Muráni Eduard

2010-08-01

Full Text Available Abstract Background Stress, elicited for example by aggressive interactions, has negative effects on various biological functions including immune defence, reproduction, growth, and, in livestock, on product quality. Stress response and aggressiveness are mutually interrelated and show large interindividual variation, partly attributable to genetic factors. In the pig little is known about the molecular-genetic background of the variation in stress responsiveness and aggressiveness. To identify candidate genes we analyzed association of DNA markers in each of ten genes (CRH g.233C>T, CRHR1 c.*866_867insA, CRHBP c.51G>A, POMC c.293_298del, MC2R c.306T>G, NR3C1 c.*2122A>G, AVP c.207A>G, AVPR1B c.1084A>G, UCN g.1329T>C, CRHR2 c.*13T>C related to the hypothalamic-pituitary-adrenocortical (HPA axis, one of the main stress-response systems, with various stress- and aggression-related parameters at slaughter. These parameters were: physiological measures of the stress response (plasma concentrations of cortisol, creatine kinase, glucose, and lactate, adrenal weight (which is a parameter reflecting activity of the central branch of the HPA axis over time and aggressive behaviour (measured by means of lesion scoring in the context of psychosocial stress of mixing individuals with different aggressive temperament. Results The SNP NR3C1 c.*2122A>G showed association with cortisol concentration (p = 0.024, adrenal weight (p = 0.003 and aggressive behaviour (front lesion score, p = 0.012; total lesion score p = 0.045. The SNP AVPR1B c.1084A>G showed a highly significant association with aggressive behaviour (middle lesion score, p = 0.007; total lesion score p = 0.003. The SNP UCN g.1329T>C showed association with adrenal weight (p = 0.019 and aggressive behaviour (front lesion score, p = 0.029. The SNP CRH g.233C>T showed a significant association with glucose concentration (p = 0.002, and the polymorphisms POMC c.293_298del and MC2R c.306T>G with adrenal

HPA axis response to psychological stress and treatment retention in residential substance abuse treatment: a prospective study.

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Daughters, Stacey B; Richards, Jessica M; Gorka, Stephanie M; Sinha, Rajita

2009-12-01

Substance abuse treatment programs are often characterized by high rates of premature treatment dropout, which increases the likelihood of relapse to drug use. Negative reinforcement models of addiction emphasize an individual's inability to tolerate stress as a key factor for understanding poor substance use treatment outcomes, and evidence indicates that dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis contributes to an individual's inability to respond adaptively to stress. The aim of the current study was to examine whether HPA axis response to stress is predictive of treatment retention among a sample of drug users in residential substance abuse treatment. Prospective study assessing treatment retention among 102 individuals enrolled in residential substance abuse treatment. Participants completed two computerized stress tasks, and HPA axis response to stress was measured via salivary cortisol at five time points from baseline (pre-stress) to 30 min post-stress exposure. The main outcome measures were treatment dropout (categorical) and total number of days in treatment (continuous). A significantly higher salivary cortisol response to stress was observed in treatment dropouts compared to treatment completers. Further, Cox proportional hazards survival analyses indicated that a higher peak cortisol response to stress was associated with a shorter number of days to treatment dropout. Results indicate that a higher salivary cortisol level in response to stress is associated with an inability to remain in substance abuse treatment. These findings are the first to document a biological marker of stress as a predictor of substance abuse treatment dropout, and support the development and implementation of treatments targeting this vulnerability.

Brain-derived neurotrophic factor and hypothalamic-pituitary-adrenal axis adaptation processes in a depressive-like state induced by chronic restraint stress.

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Naert, Gaelle; Ixart, Guy; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2011-01-01

Depression is potentially life-threatening. The most important neuroendocrine abnormality in this disorder is hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. Recent findings suggest that all depression treatments may boost the neurotrophin production especially brain-derived neurotrophic factor (BDNF). Moreover, BDNF is highly involved in the regulation of HPA axis activity. The aim of this study was to determine the impact of chronic stress (restraint 3h/day for 3 weeks) on animal behavior and HPA axis activity in parallel with hippocampus, hypothalamus and pituitary BDNF levels. Chronic stress induced changes in anxiety (light/dark box test) and anhedonic states (sucrose preference test) and in depressive-like behavior (forced swimming test); general locomotor activity and body temperature were modified and animal body weight gain was reduced by 17%. HPA axis activity was highly modified by chronic stress, since basal levels of mRNA and peptide hypothalamic contents in CRH and AVP and plasma concentrations in ACTH and corticosterone were significantly increased. The HPA axis response to novel acute stress was also modified in chronically stressed rats, suggesting adaptive mechanisms. Basal BDNF contents were increased in the hippocampus, hypothalamus and pituitary in chronically stressed rats and the BDNF response to novel acute stress was also modified. This multiparametric study showed that chronic restraint stress induced a depressive-like state that was sustained by mechanisms associated with BDNF regulation. Copyright © 2010 Elsevier Inc. All rights reserved.

Design and implementation of five-axis transformation function in CNC system

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Wang Feng

2014-04-01

Full Text Available To implement five-axis functions in CNC system, based on domestic system Lan Tian series, an improved design method for the system software structure is proposed in this paper. The numerical control kernel of CNC system is divided into the task layer and the motion layer. A five-axis transformation unit is integrated into the motion layer. After classifying five-axis machines into different types and analyzing their geometry information, the five-axis kinematic library is designed according to the abstract factory pattern. Furthermore, by taking CA spindle-tilting machine as an example, the forward and the inverse kinematic transformations are deduced. Based on the new software architecture and the five-axis kinematic library, algorithms of RTCP (rotation tool center point control and 3D radius compensation for end-milling are designed and realized. The milling results show that, with five-axis functions based on such software structure, the instructions with respect to the cutter’s position and orientation can be directly carried out in the CNC system.

Stress-induced sensitization: the hypothalamic-pituitary-adrenal axis and beyond.

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Belda, Xavier; Fuentes, Silvia; Daviu, Nuria; Nadal, Roser; Armario, Antonio

2015-01-01

Exposure to certain acute and chronic stressors results in an immediate behavioral and physiological response to the situation followed by a period of days when cross-sensitization to further novel stressors is observed. Cross-sensitization affects to different behavioral and physiological systems, more particularly to the hypothalamus-pituitary-adrenal (HPA) axis. It appears that the nature of the initial (triggering) stressor plays a major role, HPA cross-sensitization being more widely observed with systemic or high-intensity emotional stressors. Less important appears to be the nature of the novel (challenging) stressor, although HPA cross-sensitization is better observed with short duration (5-15 min) challenging stressors. In some studies with acute immune stressors, HPA sensitization appears to develop over time (incubation), but most results indicate a strong initial sensitization that progressively declines over the days. Sensitization can affect other physiological system (i.e. plasma catecholamines, brain monoamines), but it is not a general phenomenon. When studied concurrently, behavioral sensitization appears to persist longer than that of the HPA axis, a finding of interest regarding long-term consequences of traumatic stress. In many cases, behavioral and physiological consequences of prior stress can only be observed following imposition of a new stressor, suggesting long-term latent effects of the initial exposure.

HPA AXIS RELATED GENES AND RESPONSE TO PSYCHOLOGICAL THERAPIES: GENETICS AND EPIGENETICS

NARCIS (Netherlands)

Roberts, Susanna; Keers, Robert; Lester, Kathryn J.; Coleman, Jonathan R. I.; Breen, Gerome; Arendt, Kristian; Blatter-Meunier, Judith; Cooper, Peter; Creswell, Cathy; Fjermestad, Krister; Havik, Odd E.; Herren, Chantal; Hogendoorn, Sanne M.; Hudson, Jennifer L.; Krause, Karen; Lyneham, Heidi J.; Morris, Talia; Nauta, Maaike; Rapee, Ronald M.; Rey, Yasmin; Schneider, Silvia; Schneider, Sophie C.; Silverman, Wendy K.; Thastum, Mikael; Thirlwall, Kerstin; Waite, Polly; Eley, Thalia C.; Wong, Chloe C. Y.

2015-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning has been implicated in the development of stress-related psychiatric diagnoses and response to adverse life experiences. This study aimed to investigate the association between genetic and epigenetics in HPA axis and response to cognitive

Regulation of hypothalamic-pituitary-interrenal axis function in male smallmouth bass (Micropterus dolomieu) during parental care.

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Jeffrey, J D; Cooke, S J; Gilmour, K M

2014-08-01

Male smallmouth bass (Micropterus dolomieu) provide sole parental care until offspring reach independence, a period of several weeks. During the early parental care period when males are guarding fresh eggs (MG-FE), cortisol responsiveness is attenuated; the response is re-established when males reach the end of the parental care period and are guarding free-swimming fry (MG-FSF). It was hypothesized that attenuation of the cortisol response in male smallmouth bass during early parental care reflected modulation of hypothalamic-pituitary-interrenal (HPI) axis function. Male smallmouth bass were sampled at the beginning (MG-FE) and end of the parental care period (MG-FSF), before and/or 25 min after exposure to a standardized stressor consisting of 3 min of air exposure. Repeated sampling of stressed fish for analysis of plasma cortisol and adrenocorticotropic hormone (ACTH) levels was carried out. Males significantly elevated both plasma cortisol and ACTH levels when guarding free-swimming fry but not during early parental care. Control and stressed fish were terminally sampled for tissue mRNA abundance of preoptic area (POA) and hypothalamic corticotropin-releasing factor (CRF) as well as head kidney melanocortin 2 receptor (MC2R), steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc). No significant differences in either hypothalamus CRF or head kidney P450scc mRNA abundance were found across parental care stages or in response to stress. However, POA CRF mRNA abundance and interrenal cell MC2R and StAR mRNA abundances failed to increase in response to stress in MG-FE. Thus, the attenuated cortisol response in males guarding fresh eggs may be explained by hypoactive HPI axis function in response to stress. The present is one of few studies, and the first teleost study, to address the mechanisms underlying resistance to stress during the reproductive/parental care period. Copyright © 2014 Elsevier Inc. All rights

Prenatal Stress Induces Long-Term Effects in Cell Turnover in the Hippocampus-Hypothalamus-Pituitary Axis in Adult Male Rats

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Baquedano, Eva; García-Cáceres, Cristina; Diz-Chaves, Yolanda; Lagunas, Natalia; Calmarza-Font, Isabel; Azcoitia, Iñigo; Garcia-Segura, Luis M.; Argente, Jesús; Chowen, Julie A.; Frago, Laura M.

2011-01-01

Subchronic gestational stress leads to permanent modifications in the hippocampus-hypothalamus-pituitary-adrenal axis of offspring probably due to the increase in circulating glucocorticoids known to affect prenatal programming. The aim of this study was to investigate whether cell turnover is affected in the hippocampus-hypothalamus-pituitary axis by subchronic prenatal stress and the intracellular mechanisms involved. Restraint stress was performed in pregnant rats during the last week of gestation (45 minutes; 3 times/day). Only male offspring were used for this study and were sacrificed at 6 months of age. In prenatally stressed adults a decrease in markers of cell death and proliferation was observed in the hippocampus, hypothalamus and pituitary. This was associated with an increase in insulin-like growth factor-I mRNA levels, phosphorylation of CREB and calpastatin levels and inhibition of calpain -2 and caspase -8 activation. Levels of the anti-apoptotic protein Bcl-2 were increased and levels of the pro-apoptotic factor p53 were reduced. In conclusion, prenatal restraint stress induces a long-term decrease in cell turnover in the hippocampus-hypothalamus-pituitary axis that might be at least partly mediated by an autocrine-paracrine IGF-I effect. These changes could condition the response of this axis to future physiological and pathophysiological situations. PMID:22096592

Experimental hyperthyroidism and central mediators of stress axis and thyroid axis activity in common carp (Cyprinus carpio L.).

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Geven, Edwin J W; Verkaar, Folkert; Flik, Gert; Klaren, Peter H M

2006-12-01

The effect of experimental hyperthyroidism, realized by T(4) injection, on central mediators of the hypothalamo-pituitary-interrenal axis (HPI-axis) in common carp (Cyprinus carpio L.) was studied. Our results show that hyperthyroidism evokes a marked 3.2-fold reduction in basal plasma cortisol levels. Corticotropin-releasing hormone-binding protein (CRH-BP) mRNA levels in the hypothalamus, measured by real-time quantitative PCR, were significantly elevated by 40%, but CRH, urotensin-I, prepro-TRH, prohormone convertase-1 (PC1), and POMC mRNA levels were unchanged. In the pituitary pars distalis, PC1, CRH receptor-1, and POMC mRNA levels were unaffected, as was ACTH content. Plasma alpha-MSH concentrations were significantly elevated by 30% in hyperthyroid fish, and this was reflected in PC1 and POMC mRNA levels in pituitary pars intermedia that were increased 1.5- and 2.4-fold respectively. The alpha-MSH content of the pars intermedia was unchanged. Hyperthyroidism has profound effects on the basal levels of a central mediator, i.e., CRH-BP, of HPI-axis function in unstressed carp in vivo, and we conclude that HPI- and hypothalamo-pituitary-thyroid-axis functions are strongly interrelated. We suggest that the changes in plasma cortisol, thyroid hormone, and alpha-MSH levels reflect their concerted actions on energy metabolism.

Stress field models from Maxwell stress functions: southern California

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Bird, Peter

2017-08-01

The lithospheric stress field is formally divided into three components: a standard pressure which is a function of elevation (only), a topographic stress anomaly (3-D tensor field) and a tectonic stress anomaly (3-D tensor field). The boundary between topographic and tectonic stress anomalies is somewhat arbitrary, and here is based on the modeling tools available. The topographic stress anomaly is computed by numerical convolution of density anomalies with three tensor Green's functions provided by Boussinesq, Cerruti and Mindlin. By assuming either a seismically estimated or isostatic Moho depth, and by using Poisson ratio of either 0.25 or 0.5, I obtain four alternative topographic stress models. The tectonic stress field, which satisfies the homogeneous quasi-static momentum equation, is obtained from particular second derivatives of Maxwell vector potential fields which are weighted sums of basis functions representing constant tectonic stress components, linearly varying tectonic stress components and tectonic stress components that vary harmonically in one, two and three dimensions. Boundary conditions include zero traction due to tectonic stress anomaly at sea level, and zero traction due to the total stress anomaly on model boundaries at depths within the asthenosphere. The total stress anomaly is fit by least squares to both World Stress Map data and to a previous faulted-lithosphere, realistic-rheology dynamic model of the region computed with finite-element program Shells. No conflict is seen between the two target data sets, and the best-fitting model (using an isostatic Moho and Poisson ratio 0.5) gives minimum directional misfits relative to both targets. Constraints of computer memory, execution time and ill-conditioning of the linear system (which requires damping) limit harmonically varying tectonic stress to no more than six cycles along each axis of the model. The primary limitation on close fitting is that the Shells model predicts very sharp

HPA-axis stress reactivity in youth depression: evidence of impaired regulatory processes in depressed boys.

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Lopez-Duran, Nestor L; McGinnis, Ellen; Kuhlman, Kate; Geiss, Elisa; Vargas, Ivan; Mayer, Stefanie

2015-01-01

Given the link between youth depression and stress exposure, efforts to identify related biomarkers have involved examinations of stress regulation systems, including the hypothalamic-pituitary-adrenal (HPA) axis. Despite these vast efforts, the underlying mechanisms at play, as well as factors that may explain heterogeneity of past findings, are not well understood. In this study, we simultaneously examined separate components of the HPA-axis response (e.g. activation intensity, peak levels, recovery) to the Socially Evaluated Cold-Pressor Test in a targeted sample of 115 youth (age 9-16), recruited to overrepresent youth with elevated symptoms of depression. Among youth who displayed a cortisol response to the task, depression symptoms were associated with higher peak responses but not greater rate of activation or recovery in boys only. Among those who did not respond to the task, depression symptoms were associated with greater cortisol levels throughout the visit in boys and girls. Results suggest that depression symptoms are associated with a more prolonged activation of the axis and impaired recovery to psychosocial stressors primarily in boys. We discussed two potential mechanistic explanations of the link between depression symptoms and the duration of activation: (1) inhibitory shift (i.e. point at which the ratio of inhibitory and excitatory input into the axis shifts from greater excitatory to greater inhibitory input) or (2) inhibitory threshold (i.e. level of cortisol exposure required to activate the axis' feedback inhibition system).

Modifications of glucocorticoid receptors mRNA expression in the hypothalamic-pituitary-adrenal axis in response to early-life stress in female Japanese quail.

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Zimmer, C; Spencer, K A

2014-12-01

Stress exposure during early-life development can programme individual brain and physiology. The hypothalamic-pituitary-adrenal (HPA) axis is one of the primary targets of this programming, which is generally associated with a hyperactive HPA axis, indicative of a reduced negative-feedback. This reduced feedback efficiency usually results from a reduced level of the glucocorticoid receptor (GR) and/or the mineralocorticoid receptor (MR) within the HPA axis. However, a few studies have shown that early-life stress exposure results in an attenuated physiological stress response, suggesting an enhance feedback efficiency. In the present study, we aimed to determine whether early-life stress had long-term consequences on GR and MR levels in quail and whether the effects on the physiological response to acute stress observed in prenatally stressed individuals were underpinned by changes in GR and/or MR levels in one or more HPA axis components. We determined GR and MR mRNA expression in the hippocampus, hypothalamus and pituitary gland in quail exposed to elevated corticosterone during prenatal development, postnatal development, or both, and in control individuals exposed to none of the stressors. We showed that prenatal stress increased the GR:MR ratio in the hippocampus, GR and MR expression in the hypothalamus and GR expression in the pituitary gland. Postnatal stress resulted in a reduced MR expression in the hippocampus. Both early-life treatments permanently affected the expression of both receptor types in HPA axis regions. The effects of prenatal stress are in accordance with a more efficient negative-feedback within the HPA axis and thus can explain the attenuated stress response observed in these birds. Therefore, these changes in receptor density or number as a consequence of early-life stress exposure might be the mechanism that allows an adaptive response to later-life stressful conditions. © 2014 The Authors. Journal of Neuroendocrinology published by

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis.

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Evers, Andrea W M; Verhoeven, Elisabeth W M; van Middendorp, Henriët; Sweep, Fred C G J; Kraaimaat, Floris W; Donders, A Rogier T; Eijsbouts, Agnes E; van Laarhoven, Antoinette I M; de Brouwer, Sabine J M; Wirken, Lieke; Radstake, Timothy R D J; van Riel, Piet L C M

2014-09-01

Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present study was to investigate whether daily stressors and worrying as stress vulnerability factor as well as immune and HPA axis activity markers predict short-term disease activity and symptom fluctuations in patients with RA. In a prospective design, daily stressors, worrying, HPA axis (cortisol) and immune system (interleukin (IL)-1β, IL-6, IL-8, interferon (IFN)-γ, tumour necrosis factor α) markers, clinical and self-reported disease activity (disease activity score in 28 joints, RA disease activity index), and physical symptoms of pain and fatigue were monitored monthly during 6 months in 80 RA patients. Multilevel modelling indicated that daily stressors predicted increased fatigue in the next month and that worrying predicted increased self-reported disease activity, swollen joint count and pain in the next month. In addition, specific cytokines of IL-1β and IFN-γ predicted increased fatigue 1 month later. Overall, relationships remained relatively unchanged after controlling for medication use, disease duration and demographic variables. No evidence was found for immune and HPA axis activity markers as mediators of the stress-disease relationship. Daily stressors and the stress-vulnerability factor worrying predict indicators of the short-term course of RA disease activity and fatigue and pain, while specific cytokines predict short-term fluctuations of fatigue. These stress-related variables and immune markers seem to affect different aspects of disease activity or symptom fluctuations independently in RA. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Stress and serial adult metamorphosis: Multiple roles for the stress axis in socially regulated sex change

Directory of Open Access Journals (Sweden)

Tessa K Solomon-Lane

2013-11-01

Full Text Available Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis. Through actions of both corticotropin-releasing factor and glucocorticoids (GCs, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli, a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

Stress and serial adult metamorphosis: multiple roles for the stress axis in socially regulated sex change.

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Solomon-Lane, Tessa K; Crespi, Erica J; Grober, Matthew S

2013-01-01

Socially regulated sex change in teleost fishes is a striking example of social status information regulating biological function in the service of reproductive success. The establishment of social dominance in sex changing species is translated into a cascade of changes in behavior, physiology, neuroendocrine function, and morphology that transforms a female into a male, or vice versa. The hypothalamic-pituitary-interrenal axis (HPI, homologous to HP-adrenal axis in mammals and birds) has been hypothesized to play a mechanistic role linking status to sex change. The HPA/I axis responds to environmental stressors by integrating relevant external and internal cues and coordinating biological responses including changes in behavior, energetics, physiology, and morphology (i.e., metamorphosis). Through actions of both corticotropin-releasing factor and glucocorticoids, the HPA/I axis has been implicated in processes central to sex change, including the regulation of agonistic behavior, social status, energetic investment, and life history transitions. In this paper, we review the hypothesized roles of the HPA/I axis in the regulation of sex change and how those hypotheses have been tested to date. We include original data on sex change in the bluebanded goby (Lythyrpnus dalli), a highly social fish capable of bidirectional sex change. We then propose a model for HPA/I involvement in sex change and discuss how these ideas might be tested in the future. Understanding the regulation of sex change has the potential to elucidate evolutionarily conserved mechanisms responsible for translating pertinent information about the environment into coordinated biological changes along multiple body axes.

Polymorphisms of genes related to the hypothalamic-pituitary-adrenal axis influence the cortisol awakening response as well as self-perceived stress.

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Li-Tempel, Ting; Larra, Mauro F; Winnikes, Ulrike; Tempel, Tobias; DeRijk, Roel H; Schulz, André; Schächinger, Hartmut; Meyer, Jobst; Schote, Andrea B

2016-09-01

The hypothalamus-pituitary-adrenal (HPA) axis is a crucial endocrine system for coping with stress. A reliable and stable marker for the basal state of that system is the cortisol awakening response (CAR). We examined the influence of variants of four relevant candidate genes; the mineralocorticoid receptor gene (MR), the glucocorticoid receptor gene (GR), the serotonin transporter gene (5-HTT) and the gene encoding the brain-derived neurotrophic factor (BDNF) on CAR and self-perceived stress in 217 healthy subjects. We found that polymorphisms of GR influenced both, the basal state of the HPA axis as well as self-perceived stress. MR only associated with self-perceived stress and 5-HTT only with CAR. BDNF did not affected any of the investigated indices. In summary, we suggest that GR variants together with the CAR and supplemented with self reports on perceived stress might be useful indicators for the basal HPA axis activity. Copyright © 2016 Elsevier B.V. All rights reserved.

Evidence for Stress-like Alterations in the HPA-Axis in Women Taking Oral Contraceptives

DEFF Research Database (Denmark)

Hertel, Johannes; König, Johanna; Homuth, Georg

2017-01-01

Using oral contraceptives has been implicated in the aetiology of stress-related disorders like depression. Here, we followed the hypothesis that oral contraceptives deregulate the HPA-axis by elevating circulating cortisol levels. We report for a sample of 233 pre-menopausal women increased...

Maternal separation as a model of brain-gut axis dysfunction.

LENUS (Irish Health Repository)

O'Mahony, Siobhain M

2011-03-01

Early life stress has been implicated in many psychiatric disorders ranging from depression to anxiety. Maternal separation in rodents is a well-studied model of early life stress. However, stress during this critical period also induces alterations in many systems throughout the body. Thus, a variety of other disorders that are associated with adverse early life events are often comorbid with psychiatric illnesses, suggesting a common underlying aetiology. Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that is thought to involve a dysfunctional interaction between the brain and the gut. Essential aspects of the brain-gut axis include spinal pathways, the hypothalamic pituitary adrenal axis, the immune system, as well as the enteric microbiota. Accumulating evidence suggest that stress, especially in early life, is a predisposing factor to IBS.

Lithium attenuated the depressant and anxiogenic effect of juvenile social stress through mitigating the negative impact of interlukin-1β and nitric oxide on hypothalamic-pituitary-adrenal axis function.

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Haj-Mirzaian, A; Amiri, S; Kordjazy, N; Momeny, M; Razmi, A; Rahimi-Balaei, M; Amini-Khoei, H; Haj-Mirzaian, A; Marzban, H; Mehr, S E; Ghaffari, S H; Dehpour, A R

2016-02-19

The neuroimmune-endocrine dysfunction has been accepted as one of fundamental mechanisms contributing to the pathophysiology of psychiatric disorders including depression and anxiety. In this study, we aimed to evaluate the involvement of hypothalamic-pituitary-adrenal (HPA) axis, interleukin-1β, and nitrergic system in mediating the negative behavioral impacts of juvenile social isolation stress (SIS) in male mice. We also investigated the possible protective effects of lithium on behavioral and neurochemical changes in socially isolated animals. Results showed that experiencing 4-weeks of juvenile SIS provoked depressive and anxiety-like behaviors that were associated with hyper responsiveness of HPA axis, upregulation of interleukin-1β, and nitric oxide (NO) overproduction in the pre-frontal cortex and hippocampus. Administration of lithium (10 mg/kg) significantly attenuated the depressant and anxiogenic effects of SIS in behavioral tests. Lithium also restored the negative effects of SIS on cortical and hippocampal interleukin-1β and NO as well as HPA axis deregulation. Unlike the neutralizing effects of l-arginine (NO precursor), administration of l-NAME (3 mg/kg) and aminoguanidine (20 mg/kg) potentiated the positive effects of lithium on the behavioral and neurochemical profile of isolated mice. In conclusion, our results revealed that juvenile SIS-induced behavioral deficits are associated with abnormalities in HPA-immune function. Also, we suggest that alleviating effects of lithium on behavioral profile of isolated mice may be partly mediated by mitigating the negative impact of NO on HPA-immune function. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress

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Henckens, Marloes J. A. G.; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C.; van Wingen, Guido A.; Fernández, Guillén

2016-01-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both

A psychology of the human brain-gut-microbiome axis.

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Allen, Andrew P; Dinan, Timothy G; Clarke, Gerard; Cryan, John F

2017-04-01

In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain-gut-microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress-related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain-gut-microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain-gut-microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain-gut-microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain-gut-microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology.

Neurobiology of Maternal Stress: Role of Social Rank and Central Oxytocin in Hypothalamic-Pituitary Adrenal Axis Modulation

Directory of Open Access Journals (Sweden)

Jeremy D Coplan

2015-07-01

Full Text Available Background: Chronic stress may conceivably require plasticity of maternal physiology and behavior to cope with the conflicting primary demands of infant rearing and foraging for food. In addition, social rank may play a pivotal role in mandating divergent homeostatic adaptations in cohesive social groups. We examined cerebrospinal fluid (CSF oxytocin (OT levels and hypothalamic pituitary adrenal (HPA axis regulation in the context of maternal social stress and assessed the contribution of social rank to dyadic-distance as reflective of distraction from normative maternal-infant interaction. Methods: Twelve socially-housed mother-infant bonnet macaque dyads were studied after variable foraging demand (VFD exposure compared to 11 unstressed dyads. Dyadic-distance was determined by behavioral observation. Social ranking was performed blindly by two observers. Post-VFD maternal plasma cortisol and CSF OT were compared to corresponding measures in non-VFD exposed mothers. Results: High social rank was associated with increased dyadic-distance only in VFD-exposed dyads and not in control dyads. In mothers unexposed to VFD, social rank was not related to maternal cortisol levels whereas VFD-exposed dominant versus subordinate mothers exhibited increased plasma cortisol. Maternal CSF OT directly predicted maternal cortisol only in VFD-exposed mothers. CSF OT was higher in dominant versus subordinate mothers. VFD-exposed mothers with high cortisol specifically exhibited CSF OT elevations in comparison to control groups. Conclusions: Pairing of maternal social rank to dyadic-distance in VFD presumably reduces maternal contingent responsivity, with ensuing long-term sequelae. VFD-exposure dichotomizes maternal HPA axis response as a function of social rank with relatively reduced cortisol in subordinates. OT may serve as a homeostatic buffer during maternal stress exposure.

Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use: the TRAILS study

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Prince van Leeuwen, A.; Creemers, H.E.; Greaves-Lord, K.; Verhulst, F.C.; Ormel, J.; Huizink, A.C.

2011-01-01

Aims: To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design: Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco

Hypothalamic-pituitary-adrenal axis reactivity to social stress and adolescent cannabis use : the TRAILS study

NARCIS (Netherlands)

van Leeuwen, Andrea Prince; Creemers, Hanneke E.; Greaves-Lord, Kirstin; Verhulst, Frank C.; Ormel, Johan; Huizink, Anja C.

Aims To investigate the relationship of life-time and repeated cannabis use with hypothalamic-pituitary-adrenal (HPA) axis reactivity to social stress in a general population sample of adolescents. Design Adolescents who reported life-time or repeated cannabis use, life-time or repeated tobacco use

The relationship between stressful life events and Axis I diagnoses among adolescent offspring of probands with bipolar and non-bipolar psychiatric disorders and healthy controls

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Pan, Lisa A.; Goldstein, Tina R.; Rooks, Brian T.; Hickey, Mary; Fan, Jie Yu; Merranko, John; Monk, Kelly; Diler, Rasim S.; Sakolsky, Dara J.; Hafeman, Daniella; Iyengar, Satish; Goldstein, Benjamin; Kupfer, David J.; Axelson, David; Brent, David A.; Birmaher, Boris

2018-01-01

Background Previous studies have explored the role of stressful life events in the development of mood disorders. We examined the frequency and nature of stressful life events as measured by the Stressful Life Events Scale(SLES) among three groups of adolescent offspring of probands: with bipolar(BD), with non-BD psychiatric disorders, and healthy control(HC). Furthermore, we examined the relationship between stressful life events and presence of DSM-IV Axis I disorders in these offspring. Stressful life events were characterized as dependent, independent, or uncertain (neither dependent or independent), and positive, negative, and neutral (neither positive or negative). Method Offspring of probands with BD aged 13–18 years(N=269), demographically-matched offspring of probands with non-BD Axis I disorders(N=88), and HC probands(N=81) from the Pittsburgh Bipolar Offspring Study were assessed from 2002–2007 with standardized instruments at intake. Probands completed the SLES for their offspring for life events within the prior year. Life events were evaluated with regard to current offspring Axis I diagnoses after adjusting for confounds. Results After adjusting for demographic and clinical between-group differences(in probands and offspring), offspring of BD probands had greater independent and neutral life events compared with HC offspring and greater number of more severe stressful life events than HC offspring, but not non-BD offspring. Offspring of BD probands with comorbid substance use disorder reported more independent stressful life events. Greater frequency and severity of stressful life events were associated with current Axis I disorder in offspring of both BD and non-BD affected probands regardless of dependency or valence. Greater frequency and severity of stressful life events were associated with greater current Axis I disorder in all offspring. Conclusions Offspring of BD probands have greater exposure to independent and neutral life events than

Stress in adolescence and drugs of abuse in rodent models: Role of dopamine, CRF, and HPA axis

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Burke, Andrew R.; Miczek, Klaus A.

2014-01-01

Rationale Research on adolescence and drug abuse increased substantially in the past decade. However, drug-addiction related behaviors following stressful experiences during adolescence are less studied. We focus on rodent models of adolescent stress cross-sensitization to drugs of abuse. Objectives Review the ontogeny of behavior, dopamine, corticotropin-releasing factor (CRF), and the hypothalamic pituitary adrenal (HPA) axis in adolescent rodents. We evaluate evidence that stressful experiences during adolescence engender hypersensitivity to drugs of abuse and offer potential neural mechanisms. Results and Conclusions Much evidence suggests that final maturation of behavior, dopamine systems, and HPA axis occurs during adolescence. Stress during adolescence increases amphetamine- and ethanol-stimulated locomotion, preference, and self-administration under many conditions. The influence of adolescent stress on subsequent cocaine- and nicotine-stimulated locomotion and preference is less clear. The type of adolescent stress, temporal interval between stress and testing, species, sex, and the drug tested are key methodological determinants for successful cross-sensitization procedures. The sensitization of the mesolimbic dopamine system is proposed to underlie stress cross-sensitization to drugs of abuse in both adolescents and adults through modulation by CRF. Reduced levels of mesocortical dopamine appear to be a unique consequence of social stress during adolescence. Adolescent stress may reduce the final maturation of cortical dopamine through D2 dopamine receptor regulation of dopamine synthesis or glucocorticoid-facilitated pruning of cortical dopamine fibers. Certain rodent models of adolescent adversity are useful for determining neural mechanisms underlying the cross-sensitization to drugs of abuse. PMID:24370534

Lithium-induced malaise does not interfere with adaptation of the hypothalamic-pituitary-adrenal axis to stress.

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Sanchís-Ollé, Maria; Ortega-Sánchez, Juan A; Belda, Xavier; Gagliano, Humberto; Nadal, Roser; Armario, Antonio

2017-04-03

We have recently demonstrated that adaptation of the hypothalamic-pituitary-adrenal (HPA) axis to repeated exposure to a stressor does not follow the rules of habituation and can be fully expressed after a single experience with severe stressors. In the present work we tested the hypothesis that adaptation could be impaired if animals experience malaise during initial exposure to the stressor. To this end, animals were allowed to drink saccharin for 30min before being exposed for 3h to immobilization on boards (IMO), a severe stressor; then they were given either saline or lithium ip after the first hour of IMO. Stress-naïve rats followed exactly the same procedure except IMO. Exposure to IMO caused a strong activation of the HPA axis whereas the effect of lithium was modest. Both IMO and lithium administration resulted in conditioned taste aversion to saccharin when evaluated 4days later. When all animals were exposed to IMO 6days later, reduced HPA response and less impact on body weight was observed in the two groups previously exposed to IMO as compared with stress-naïve rats. Therefore, lithium administration during the first IMO exposure did not affect adaptation of the HPA axis and weight gain. These results indicate that malaise per se only weakly activated the HPA axis and argue against the hypothesis that signs of physical malaise during exposure to the stressor could impair HPA adaptation. Copyright © 2017 Elsevier Inc. All rights reserved.

Functional Implications of the IL-23/IL-17 Immune Axis in Schizophrenia.

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Debnath, Monojit; Berk, Michael

2017-12-01

The aetiology of schizophrenia seems to stem from complex interactions amongst environmental, genetic, metabolic, immunologic and oxidative components. Chronic low-grade inflammation has been persistently linked to schizophrenia, and this has primarily been based on the findings derived from Th1/Th2 cytokine balance. While the IL-23/IL-17 axis plays crucial role in the pathogenesis of several immune-mediated disorders, it has remained relatively unexplored in neuropsychiatric disorders. Altered levels of cytokines related to IL-23/IL-17 axis have been observed in schizophrenia patients in a few studies. In addition, other indirect factors known to confer schizophrenia risk like complement activation and altered gut microbiota are shown to modulate the IL-23/IL-17 axis. These preliminary observations provide crucial clues about the functional implications of IL-23/IL-17 axis in schizophrenia. In this review, an attempt has been made to highlight the biology of IL-23/IL-17 axis and its relevance to schizophrenia risk and pathogenesis. Given the pathogenic potential of the IL-23/IL-17 axis, therapeutic targeting of this axis may be a promising approach to benefit patients suffering from this devastating disorder.

Psychological Stress and the Cutaneous Immune Response: Roles of the HPA Axis and the Sympathetic Nervous System in Atopic Dermatitis and Psoriasis

Directory of Open Access Journals (Sweden)

Jessica M. F. Hall

2012-01-01

Full Text Available Psychological stress, an evolutionary adaptation to the fight-or-flight response, triggers a number of physiological responses that can be deleterious under some circumstances. Stress signals activate the hypothalamus-pituitary-adrenal (HPA axis and the sympathetic nervous system. Elements derived from those systems (e.g., cortisol, catecholamines and neuropeptides can impact the immune system and possible disease states. Skin provides a first line of defense against many environmental insults. A number of investigations have indicated that the skin is especially sensitive to psychological stress, and experimental evidence shows that the cutaneous innate and adaptive immune systems are affected by stressors. For example, psychological stress has been shown to reduce recovery time of the stratum corneum barrier after its removal (innate immunity and alters antigen presentation by epidermal Langerhans cells (adaptive immunity. Moreover, psychological stress may trigger or exacerbate immune mediated dermatological disorders. Understanding how the activity of the psyche-nervous -immune system axis impinges on skin diseases may facilitate coordinated treatment strategies between dermatologists and psychiatrists. Herein, we will review the roles of the HPA axis and the sympathetic nervous system on the cutaneous immune response. We will selectively highlight how the interplay between psychological stress and the immune system affects atopic dermatitis and psoriasis.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder.

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Cooper, Odelia; Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-06-01

Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Prospective controlled study in an outpatient clinic. Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm 3 [standard deviation (SD), 227.3 mm 3 ] in PTSD subjects vs 835.2 mm 3 (SD, 302.8 mm 3 ) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects ( P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches.

Altered Pituitary Gland Structure and Function in Posttraumatic Stress Disorder

Science.gov (United States)

Bonert, Vivien; Moser, Franklin; Mirocha, James; Melmed, Shlomo

2017-01-01

Objectives: Posttraumatic stress disorder (PTSD) is associated with hypothalamus-pituitary-adrenal (HPA) axis response to stressors, but links to neurophysiological and neuroanatomical changes are unclear. The purpose of this study was to determine whether stress-induced cortisol alters negative feedback on pituitary corticotroph function and pituitary volume. Design: Prospective controlled study in an outpatient clinic. Methods: Subjects with PTSD and matched control subjects underwent pituitary volume measurement on magnetic resonance imaging, with pituitary function assessed by 24-hour urine free cortisol (UFC), 8:00 am cortisol, and adrenocorticotropic hormone (ACTH) levels, and ACTH levels after 2-day dexamethasone/corticotropin-releasing hormone test. Primary outcome was pituitary volume; secondary outcomes were ACTH area under the curve (AUC) and 24-hour UFC. Results: Thirty-nine subjects were screened and 10 subjects with PTSD were matched with 10 healthy control subjects by sex and age. Mean pituitary volume was 729.7 mm3 [standard deviation (SD), 227.3 mm3] in PTSD subjects vs 835.2 mm3 (SD, 302.8 mm3) in control subjects. ACTH AUC was 262.5 pg/mL (SD, 133.3 pg/mL) L in PTSD vs 244.0 pg/mL (SD, 158.3 pg/mL) in control subjects (P = 0.80). In PTSD subjects, UFC levels and pituitary volume inversely correlated with PTSD duration; pituitary volume correlated with ACTH AUC in control subjects (Pearson correlation coefficient, 0.88, P = 0.0009) but not in PTSD subjects. Conclusions: The HPA axis may be downregulated and dysregulated in people with PTSD, as demonstrated by discordant pituitary corticotroph function and pituitary volume vs intact HPA feedback and correlation of pituitary volume with ACTH levels in healthy control subjects. The results suggest a link between pituitary structure and function in PTSD, which may point to endocrine targeted therapeutic approaches. PMID:29264511

Early-life social experiences in mice affect emotional behaviour and hypothalamic-pituitary-adrenal axis function.

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Ros-Simó, Clara; Valverde, Olga

2012-09-01

Early-life stressful experiences are associated to alterations in behavioural responses and development of psychiatric and neurodegenerative diseases. In rodents, individual housing is considered as a stressful condition whilst enriched environment can protect against stress and its negative consequences. Neuroendocrine responses to stress can also be altered by early-life experiences and seem to contribute to behavioural alterations induced by changes in housing conditions. To develop an improved procedure of social isolation throughout development (from pre-adolescence to adulthood) in CD1 mice and to elucidate its effects on behavioural parameters related to stress and neuroendocrine responses compared to enriched or social conditions. CD1 male mice (PND 21) were housed in social/standard conditions, enriched conditions or isolated conditions during seven weeks. After that, different relevant behaviours were evaluated, including locomotor activity, anxiety-like and despair behaviour. Levels of plasma corticosterone were also analysed before and after a stressful event. CD1 mice exposed to an isolated environment exhibited higher locomotion and anxiety-like responses than animals exposed to social or enriched conditions. In addition, isolated animals showed lower basal plasma corticosterone than social or enriched ones but after a stressful event the elevation of plasma corticosterone was higher, suggesting an enhanced response of the HPA axis to a novel and stressful situation. Social interaction is an important feature to display an appropriate behavioural and neuronal development. Habituation to novel stimuli is impaired in subjects exposed to social isolation and induces increased excitability response to stressful events. Social deprivation increases the possibility of altered neuronal function and could facilitate the development of neuropsychiatric disorders in adulthood. Copyright © 2012 Elsevier Inc. All rights reserved.

Corticotropin releasing hormone and imaging, rethinking the stress axis

International Nuclear Information System (INIS)

Contoreggi, Carlo

2015-01-01

The stress system provides integration of both neurochemical and somatic physiologic functions within organisms as an adaptive mechanism to changing environmental conditions throughout evolution. In mammals and primates the complexity and sophistication of these systems have surpassed other species in triaging neurochemical and physiologic signaling to maximize chances of survival. Corticotropin releasing hormone (CRH) and its related peptides and receptors have been identified over the last three decades and are fundamental molecular initiators of the stress response. They are crucial in the top down regulatory cascade over a myriad of neurochemical, neuroendocrine and sympathetic nervous system events. From neuroscience, we've seen that stress activation impacts behavior, endocrine and somatic physiology and influences neurochemical events that one can capture in real time with current imaging technologies. To delineate these effects one can demonstrate how the CRH neuronal networks infiltrate critical cognitive, emotive and autonomic regions of the central nervous system (CNS) with somatic effects. Abundant preclinical and clinical studies show inter-regulatory actions of CRH with multiple neurotransmitters/peptides. Stress, both acute and chronic has epigenetic effects which magnify genetic susceptibilities to alter neurochemistry; stress system activation can add critical variables in design and interpretation of basic and clinical neuroscience and related research. This review will attempt to provide an overview of the spectrum of known functions and speculative actions of CRH and stress responses in light of imaging technology and its interpretation. Metabolic and neuroreceptor positron emission/single photon tomography (PET/SPECT), functional magnetic resonance imaging (fMRI), anatomic MRI, diffusion tensor imaging (DTI), and proton magnetic resonance spectroscopy (pMRS) are technologies that can delineate basic mechanisms of neurophysiology and

Effects of Early-Life Adversity on Hippocampal Structures and Associated HPA Axis Functions.

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Dahmen, Brigitte; Puetz, Vanessa B; Scharke, Wolfgang; von Polier, Georg G; Herpertz-Dahlmann, Beate; Konrad, Kerstin

2018-01-01

Early-life adversity (ELA) is one of the major risk factors for serious mental and physical health risks later in life. ELA has been associated with dysfunctional neurodevelopment, especially in brain structures such as the hippocampus, and with dysfunction of the stress system, including the hypothalamic-pituitary-adrenal (HPA) axis. Children who have experienced ELA are also more likely to suffer from mental health disorders such as depression later in life. The exact interplay of aberrant neurodevelopment and HPA axis dysfunction as risks for psychopathology is not yet clear. We investigated volume differences in the bilateral hippocampus and in stress-sensitive hippocampal subfields, behavior problems, and diurnal cortisol activity in 24 children who had experienced documented ELA (including out-of-home placement) in a circumscribed duration of adversity only in their first 3 years of life in comparison to data on 25 control children raised by their biological parents. Hippocampal volumes and stress-sensitive hippocampal subfields (Cornu ammonis [CA]1, CA3, and the granule-cell layer of the dentate gyrus [GCL-DG]) were significantly smaller in children who had experienced ELA, taking psychiatric diagnoses and dimensional psychopathological symptoms into account. ELA moderated the relationship between left hippocampal volume and cortisol: in the control group, hippocampal volumes were not related to diurnal cortisol, while in ELA children, a positive linear relationship between left hippocampal volume and diurnal cortisol was present. Our findings show that ELA is associated with altered development of the hippocampus, and an altered relationship between hippocampal volume and HPA axis activity in youth in care, even after they have lived in stable and caring foster family environments for years. Altered hippocampal development after ELA could thus be associated with a risk phenotype for the development of psychiatric disorders later in life. © 2017 S. Karger

A Miniature Magnetic-Force-Based Three-Axis AC Magnetic Sensor with Piezoelectric/Vibrational Energy-Harvesting Functions

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Chiao-Fang Hung

2017-02-01

Full Text Available In this paper, we demonstrate a miniature magnetic-force-based, three-axis, AC magnetic sensor with piezoelectric/vibrational energy-harvesting functions. For magnetic sensing, the sensor employs a magnetic–mechanical–piezoelectric configuration (which uses magnetic force and torque, a compact, single, mechanical mechanism, and the piezoelectric effect to convert x-axis and y-axis in-plane and z-axis magnetic fields into piezoelectric voltage outputs. Under the x-axis magnetic field (sine-wave, 100 Hz, 0.2–3.2 gauss and the z-axis magnetic field (sine-wave, 142 Hz, 0.2–3.2 gauss, the voltage output with the sensitivity of the sensor are 1.13–26.15 mV with 8.79 mV/gauss and 1.31–8.92 mV with 2.63 mV/gauss, respectively. In addition, through this configuration, the sensor can harness ambient vibrational energy, i.e., possessing piezoelectric/vibrational energy-harvesting functions. Under x-axis vibration (sine-wave, 100 Hz, 3.5 g and z-axis vibration (sine-wave, 142 Hz, 3.8 g, the root-mean-square voltage output with power output of the sensor is 439 mV with 0.333 μW and 138 mV with 0.051 μW, respectively. These results show that the sensor, using this configuration, successfully achieves three-axis magnetic field sensing and three-axis vibration energy-harvesting. Due to these features, the three-axis AC magnetic sensor could be an important design reference in order to develop future three-axis AC magnetic sensors, which possess energy-harvesting functions, for practical industrial applications, such as intelligent vehicle/traffic monitoring, processes monitoring, security systems, and so on.

Multi-level risk factors for suicidal ideation among at-risk adolescent females : The role of hypothalamic-pituitary-adrenal axis responses to stress

NARCIS (Netherlands)

Giletta, M.; Calhoun, C.D.; Hastings, P.D.; Rudolph, K.D.; Nock, M.K.; Prinstein, M.J.

2015-01-01

Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological,

Does stress affect the joints? Daily stressors, stress vulnerability, immune and HPA axis activity, and short-term disease and symptom fluctuations in rheumatoid arthritis

NARCIS (Netherlands)

Evers, A.W.M.; Verhoeven, E.W.M.; Middendorp, H. van; Sweep, F.C.; Kraaimaat, F.W.; Donders, A.R.T.; Eijsbouts, A.E.; Laarhoven, A.I.M. van; Brouwer, S.J.M. de; Wirken, L.; Radstake, T.R.D.J.; Riel, P.L.C.M. van

2014-01-01

OBJECTIVES: Both stressors and stress vulnerability factors together with immune and hypothalamus-pituitary-adrenal (HPA) axis activity components have been considered to contribute to disease fluctuations of chronic inflammatory diseases, such as rheumatoid arthritis (RA). The aim of the present

Early life trauma and attachment: Immediate and enduring effects on neurobehavioral and stress axis development

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Millie eRincón-Cortés

2014-03-01

Full Text Available Over half a century of converging clinical and animal research indicates that early life experiences induce enduring neuroplasticity of the HPA-axis and the developing brain. This experience-induced neuroplasticity is due to alterations in the frequency and intensity of stimulation of pups’ sensory systems (i.e. olfactory, somatosensory, gustatory embedded in mother-infant interactions. This stimulation provides hidden regulators of pups’ behavioral, physiological and neural responses that have both immediate and enduring consequences, including those involving the stress response. While variation in stimulation can produce individual differences and adaptive behaviors, pathological early life experiences can induce maladaptive behaviors, initiate a pathway to pathology and increase risk for later life psychopathologies, such as mood and affective disorders, suggesting that infant attachment relationships program later life neurobehavioral function. Recent evidence suggests that the effects of maternal presence or absence during this sensory stimulation provide a major modulatory role in neural and endocrine system responses, which have minimal impact on pups’ immediate neurobehavior but a robust impact on neurobehavioral development. This concept is reviewed here using two complementary rodent models of infant trauma within attachment: infant paired odor-shock conditioning (mimicking maternal odor attachment learning and rearing with an abusive mother, that converge in producing a similar behavioral phenotype in later life including depressive-like behavior as well as disrupted HPA-axis and amygdala function. The importance of maternal social presence on pups’ immediate and enduring brain and behavior suggests unique processing of sensory stimuli in early life that could provide insight into the development of novel strategies for prevention and therapeutic interventions for trauma experienced with the abusive caregiver.

Effects of experimentally induced hyperthyroidism on central hypothalamic-pituitary-adrenal axis function in rats: in vitro and in situ studies.

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Johnson, Elizabeth O; Calogero, Aldo E; Konstandi, Maria; Kamilaris, Themis C; La Vignera, Sandro; Vignera, Sandro La; Chrousos, George P

2013-06-01

Hyperthyroidism is associated with hypercorticosteronemia, although the locus that is principally responsible for the hypercorticosteronism remains unclear. The purpose of this study was to assess the effects of hyperthyroidism on the functional integrity of the hypothalamic-pituitary-adrenal (HPA) axis, to identify the locus in the HPA axis that is principally affected, and address the time-dependent effects of alterations in thyroid status. The functional integrity of each component of the HPA axis was examined in vitro and in situ in sham-thyroidectomized male Sprague-Dawley rats given placebo or in thyroidectomized rats given pharmacological dose (50 μg) of thyroxin for 7 or 60 days. Basal plasma corticosterone and corticosterone binding globulin (CBG) concentrations were significantly increased in short- and long-term hyperthyroid rats, and by 60 days. Basal plasma ACTH levels were similar to controls. Both hypothalamic CRH content and the magnitude of KCL- and arginine vasopressin (AVP)-induced CRH release from hypothalamic culture were increased in long-term hyperthyroid rats. There was a significant increase in the content of both ACTH and β-endorphin in the anterior pituitaries of both short- and long-term hyperthyroid animals. Short-term hyperthyroid rats showed a significant increase in basal POMC mRNA expression in the anterior pituitary, and chronically hyperthyroid animals showed increased stress-induced POMC mRNA expression. Adrenal cultures taken from short-term hyperthyroid rats responded to exogenous ACTH with an exaggerated corticosterone response, while those taken from 60-day hyperthyroid animals showed responses similar to controls. The findings show that hyperthyroidism is associated with hypercorticosteronemia and HPA axis dysfunction that becomes more pronounced as the duration of hyperthyroidism increases. The evidence suggests that experimentally induced hyperthyroidism is associated with central hyperactivity of the HPA axis.

Effects of ginseng on stress-related depression, anxiety, and the hypothalamic–pituitary–adrenal axis

Directory of Open Access Journals (Sweden)

Seungyeop Lee

2017-10-01

Full Text Available Ginseng effectively regulates the immune response and the hormonal changes due to stress, thus maintaining homeostasis. In addition to suppressing the occurrence of psychological diseases such as anxiety and depression, ginseng also prevents stress-associated physiological diseases. Recent findings have revealed that ginseng is involved in adjusting the hypothalamic–pituitary–adrenal axis and controlling hormones, thus producing beneficial effects on the heart and brain, and in cases of bone diseases, as well as alleviating erectile dysfunction. Recent studies have highlighted the potential use of ginseng in the prevention and treatment of chronic inflammatory diseases such as diabetes, rheumatoid arthritis, and allergic asthma. However, the mechanism underlying the effects of ginseng on these stress-related diseases has not been completely established. In this review, we focus on the disease pathways caused by stress in order to determine how ginseng acts to improve health. Central to our discussion is how this effective and stable therapeutic agent alleviates the anxiety and depression caused by stress and ameliorates inflammatory diseases.

Interpolation of magnetic surface functions for an axi-symmetric plasma

International Nuclear Information System (INIS)

Yamaguchi, Taiki; Maeyama, Mitsuaki

2000-01-01

Informations of the magnetic surface functions of magnetically confined plasma are indispensable for equilibrium, stability and transport analyses. In this paper, in order to identify a realistic surface functions and compare those with ones which are introduced from Taylor's relaxation theory, we propose a code to interpolate these surface functions for an axi-symmetric plasma from experimentally measured data. To confirm our code, we used the date which were analyzed from known functions given as a measured data. As a result, we have developed a code which can derive surface functions I and P. Effects of measurement error on those functions are also examined. (author)

Late-Onset Cognitive Impairments after Early-Life Stress Are Shaped by Inherited Differences in Stress Reactivity

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McIlwrick, Silja; Pohl, Tobias; Chen, Alon; Touma, Chadi

2017-01-01

Early-life stress (ELS) has been associated with lasting cognitive impairments and with an increased risk for affective disorders. A dysregulation of the hypothalamus-pituitary-adrenal (HPA) axis, the body’s main stress response system, is critically involved in mediating these long-term consequences of adverse early-life experience. It remains unclear to what extent an inherited predisposition for HPA axis sensitivity or resilience influences the relationship between ELS and cognitive impairments, and which neuroendocrine and molecular mechanisms may be involved. To investigate this, we exposed animals of the stress reactivity mouse model, consisting of three independent lines selectively bred for high (HR), intermediate (IR), or low (LR) HPA axis reactivity to a stressor, to ELS and assessed their cognitive performance, neuroendocrine function and hippocampal gene expression in early and in late adulthood. Our results show that HR animals that were exposed to ELS exhibited an HPA axis hyper-reactivity in early and late adulthood, associated with cognitive impairments in hippocampus-dependent tasks, as well as molecular changes in transcript levels involved in the regulation of HPA axis activity (Crh) and in neurotrophic action (Bdnf). In contrast, LR animals showed intact cognitive function across adulthood, with no change in stress reactivity. Intriguingly, LR animals that were exposed to ELS even showed significant signs of enhanced cognitive performance in late adulthood, which may be related to late-onset changes observed in the expression of Crh and Crhr1 in the dorsal hippocampus of these animals. Collectively, our findings demonstrate that the lasting consequences of ELS at the level of cognition differ as a function of inherited predispositions and suggest that an innate tendency for low stress reactivity may be protective against late-onset cognitive impairments after ELS. PMID:28261058

Early experience and sex interact to influence limbic-hypothalamic-pituitary-adrenal-axis function after acute alcohol administration in rhesus macaques (Macaca mulatta).

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Barr, C S; Newman, T K; Lindell, S; Becker, M L; Shannon, C; Champoux, M; Suomi, S J; Higley, J D

2004-07-01

Studies in rodents demonstrate sex differences in neuroendocrine stress axis activity after treatment with alcohol. In abstinent alcoholics, atypical depressives, and individuals with posttraumatic stress disorder, limbic-hypothalamic-pituitary-adrenal (LHPA)-axis activity is often blunted; among females in these patient populations, however, resistance to glucocorticoid feedback and increased pituitary reactivity is observed. Early parental loss is a major life stressor and is a risk factor for both affective disturbances and LHPA-axis abnormalities later in life. We wanted to determine whether sex and early life parental absence would interact to influence alcohol-induced alterations in LHPA-axis activity after exposure to ethanol in macaques. Animals were reared with their mothers in social groups (MR, n = 94) or without adults in peer-only groups (PR, n = 79). At 5 years of age, they received an intravenous infusion of alcohol (2-2.2 g/kg), and the effects of alcohol, sex, and rearing condition on ACTH and cortisol levels were analyzed by ANOVA. Peer-reared females had higher ACTH levels than did PR males, MR females, and MR males after alcohol infusion. Alcohol-induced cortisol levels were not affected by sex and rearing condition. These findings suggest that there are sex differences in glucocorticoid negative feedback, pituitary responsivity, or release of ACTH secretagogues among individuals exposed to early life stress and emphasize the importance of considering sex effects when studying LHPA-axis dysregulation in alcoholism and other stress-related neuropsychiatric disorders.

HPA axis response to social stress is attenuated in schizophrenia but normal in depression: evidence from a meta-analysis of existing studies.

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Ciufolini, Simone; Dazzan, Paola; Kempton, Matthew J; Pariante, Carmine; Mondelli, Valeria

2014-11-01

We conducted a meta-analysis to investigate the HPA axis response to social stress in studies that used the Trier Social Stress Test (TSST), or comparable distressing paradigms, in individuals with either depression or schizophrenia. Sample size-adjusted effect sizes (Hedge's g statistic) were calculated to estimate the HPA axis stress response to social stress. We used a meta-regression model to take into account the moderating effect of the baseline cortisol level. Participants with depression show an activation pattern to social stress similar to that of healthy controls. Despite a normal cortisol production rate, individuals with schizophrenia have lower cortisol levels than controls both in anticipation and after exposure to social stress. Participants with depression and higher cortisol levels before the task have an increased cortisol production and reached higher cortisol levels during the task. This may be explained by the presence of an impaired negative feedback. The activation pattern present in schizophrenia may explain the reduced ability to appropriately contextualize past experiences shown by individuals with psychosis in social stressful situation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neuroepigenetics of stress.

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Griffiths, B B; Hunter, R G

2014-09-05

Stress, a common if unpredictable life event, can have pronounced effects on physiology and behavior. Individuals show wide variation in stress susceptibility and resilience, which are only partially explained by variations in coding genes. Developmental programing of the hypothalamic-pituitary-adrenal stress axis provides part of the explanation for this variance. Epigenetic approaches have successfully helped fill the explanatory gaps between the influences of gene and environment on stress responsiveness, and differences in the sequelae of stress across individuals and generations. Stress and the stress axis interacts bi-directionally with epigenetic marks within the brain. It is now clear that exposure to stress, particularly in early life, has both acute and lasting effects on these marks. They in turn influence cognitive function and behavior, as well as the risk for suicide and psychiatric disorders across the lifespan and, in some cases, unto future generations. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Activation of the Tor/Myc signaling axis in intestinal stem and progenitor cells affects longevity, stress resistance and metabolism in drosophila.

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Strilbytska, Olha M; Semaniuk, Uliana V; Storey, Kenneth B; Edgar, Bruce A; Lushchak, Oleh V

2017-01-01

The TOR (target of rapamycin) signaling pathway and the transcriptional factor Myc play important roles in growth control. Myc acts, in part, as a downstream target of TOR to regulate the activity and functioning of stem cells. Here we explore the role of TOR-Myc axis in stem and progenitor cells in the regulation of lifespan, stress resistance and metabolism in Drosophila. We found that both overexpression of rheb and myc-rheb in midgut stem and progenitor cells decreased the lifespan and starvation resistance of flies. TOR activation caused higher survival under malnutrition conditions. Furthermore, we demonstrate gut-specific activation of JAK/STAT and insulin signaling pathways to control gut integrity. Both genetic manipulations had an impact on carbohydrate metabolism and transcriptional levels of metabolic genes. Our findings indicate that activation of the TOR-Myc axis in midgut stem and progenitor cells influences a variety of traits in Drosophila. Copyright © 2016 Elsevier Inc. All rights reserved.

Stress and the hypothalamus-pituitary-gonadal axis in the cyclic rat

NARCIS (Netherlands)

Roozendaal, M.M.

1997-01-01

The influence of stress on reproductive functions has been subject of much research. Various kinds of stress are known to affect reproductive functions. In females, the complex regulation of the ovarian cycle relies on a series of neuroendocrine events whose temporal relationship is so

Dopamine D1 and D2 dopamine receptors regulate immobilization stress-induced activation of the hypothalamus-pituitary-adrenal axis.

Science.gov (United States)

Belda, Xavier; Armario, Antonio

2009-10-01

Whereas the role of most biogenic amines in the control of the hypothalamus-pituitary-adrenal (HPA) response to stress has been extensively studied, the role of dopamine has not. We studied the effect of different dopamine receptor antagonists on HPA response to a severe stressor (immobilization, IMO) in adult male Sprague-Dawley rats. Haloperidol administration reduced adrenocorticotropin hormone and corticosterone responses to acute IMO, particularly during the post-IMO period. This effect cannot be explained by a role of dopamine to maintain a sustained activation of the HPA axis as haloperidol did not modify the response to prolonged (up to 6 h) IMO. Administration of more selective D1 and D2 receptor antagonists (SCH23390 and eticlopride, respectively) also resulted in lower and/or shorter lasting HPA response to IMO. Dopamine, acting through both D1 and D2 receptors, exerts a stimulatory role on the activation of the HPA axis in response to a severe stressor. The finding that dopamine is involved in the maintenance of post-stress activation of the HPA axis is potentially important because the actual pathological impact of HPA activation is likely to be related to the area under the curve of plasma glucocorticoid levels, which is critically dependent on how long after stress high levels of glucocorticoid are maintained.

A novel stress isolation guard-ring design for the improvement of a three-axis piezoresistive accelerometer

International Nuclear Information System (INIS)

Hsieh, Hsieh-Shen; Chang, Heng-Chung; Hu, Chih-Fan; Cheng, Chao-Lin; Fang, Weileun

2011-01-01

This study designs and implements a stress isolation guard-ring structure to improve the performances of the existing single proof-mass three-axis piezoresistive accelerometer. Thus, the environment disturbances, such as temperature variation and force/deflection transmittance, for a packaged three-axis piezoresistive accelerometer are significantly reduced. In application, the three-axis piezoresistive accelerometer has been fabricated using the bulk micromachining process on the SOI wafer. Experimental results show that the out-of-plane deformation of the suspended spring mass on the packaged accelerometer is reduced from 0.72 to 0.10 µm at a 150 °C temperature elevation. The temperature coefficient of zero-g offset for the presented sensor is reduced, and the temperature-induced sensitivity variation is minimized as well. Measurements also demonstrate that the guard-ring design successfully reduces the false signals induced by the force and displacement transmittance disturbances for one order of magnitude. Moreover, the three-axis acceleration sensing for the presented accelerometer with guard ring has also been demonstrated with sensitivities of 0.12–0.17 mV V −1 g −1 and nonlinearity < 1.02%.

BDNF Val66Met polymorphism is associated with HPA axis reactivity to psychological stress characterized by genotype and gender interactions.

Science.gov (United States)

Shalev, Idan; Lerer, Elad; Israel, Salomon; Uzefovsky, Florina; Gritsenko, Inga; Mankuta, David; Ebstein, Richard P; Kaitz, Marsha

2009-04-01

A key protein in maintaining neuronal integrity throughout the life span is brain-derived neurotrophic factor (BDNF). The BDNF gene is characterized by a functional polymorphism, which has been associated with stress-related disorders such as anxiety-related syndromes and depression, prompting us to examine individual responses by Genotype and Sex to a standardized social stress paradigm. Gender differences in BDNFxstress responses were posited because estrogen induces synthesis of BDNF in several brain regions. 97 university students (51 females and 46 males) participated in a social stress procedure (Trier Social Stress Test, TSST). Indices of stress were derived from repeated measurement of cortisol, blood pressure, and heart rate during the TSST. All subjects were genotyped for the Val66Met polymorphism. Tests of within-subject effects showed a significant three-way interaction (SPSS GLM repeated measures: Time (eight levels)xBDNF (val/val, val/met)xSex: p=0.0002), which reflects gender differences in the pattern of cortisol rise and decline during the social challenge. In male subjects, val/val homozygotes showed a greater rise in salivary cortisol than val/met heterozygotes. In female subjects, there was a trend for the opposite response, which is significant when area under the curve increase (AUCi) was calculated for the val/val homozygotes to show the lowest rise. Overall, the same pattern of results was observed for blood pressure and heart rate. These results indicate that a common, functionally significant polymorphism in the BDNF gene modulates HPA axis reactivity and regulation during the TSST differently in men and women. Findings may be related to gender differences in reactivity and vulnerability to social stress.

Multi-Level Risk Factors for Suicidal Ideation Among at-Risk Adolescent Females: The Role of Hypothalamic-Pituitary-Adrenal Axis Responses to Stress

Science.gov (United States)

Calhoun, Casey D.; Hastings, Paul D.; Rudolph, Karen D.; Nock, Matthew K.; Prinstein, Mitchell J.

2014-01-01

Adopting a multi-level approach, this study examined risk factors for adolescent suicidal ideation, with specific attention to (a) hypothalamic-pituitary-adrenal (HPA) axis stress responses and (b) the interplay between HPA-axis and other risk factors from multiple domains (i.e., psychological, interpersonal and biological). Participants were 138 adolescent females (Mage=14.13 years, SD=1.40) at risk for suicidal behaviors. At baseline, lifetime suicidal ideation and a number of risk factors were assessed (i.e., depressive symptoms, impulsiveness, pubertal status and peer stress). Participants were exposed to a psychosocial stress task and HPA-axis responses were assessed by measuring cortisol levels pre- and post-stressor. At 3 months post-baseline, suicidal ideation again was assessed. Using group-based trajectory modeling, three groups of cortisol stress-response patterns were identified (i.e., hyporesponsive, normative, and hyperresponsive). As compared to females in the normative and hyporesponsive group, females in the hyperresponsive group were more likely to report a lifetime history of suicidal ideation at baseline, above and beyond the effects of the other predictors. Moreover, as compared to females in the normative group, females in the hyperresponsive group were at increased risk for reporting suicidal ideation 3 months later, after controlling for prior ideation. No interactions between cortisol group and the other risk factors were significant, with the exception of a non-significant trend between impulsiveness and cortisol group on lifetime suicidal ideation. Findings highlight the importance of HPA-axis responses to acute stressors as a risk factor for suicidal ideation among adolescents. PMID:24958308

Involvement of Endogenous Brain-Derived Neurotrophic Factor in Hypothalamic-Pituitary-Adrenal Axis Activity.

Science.gov (United States)

Naert, G; Zussy, C; Tran Van Ba, C; Chevallier, N; Tang, Y-P; Maurice, T; Givalois, L

2015-11-01

Brain-derived neurotrophic factor (BDNF) appears to be highly involved in hypothalamic-pituitary-adrenal (HPA) axis regulation during adulthood, playing an important role in homeostasis maintenance. The present study aimed to determine the involvement of BDNF in HPA axis activity under basal and stress conditions via partial inhibition of this endogenous neurotrophin. Experiments were conducted in rats and mice with two complementary approaches: (i) BDNF knockdown with stereotaxic delivery of BDNF-specific small interfering RNA (siRNA) into the lateral ventricle of adult male rats and (ii) genetically induced knockdown (KD) of BDNF expression specifically in the central nervous system during the first ontogenesis in mice (KD mice). Delivery of siRNA in the rat brain decreased BDNF levels in the hippocampus (-31%) and hypothalamus (-35%) but not in the amygdala, frontal cortex and pituitary. In addition, siRNA induced no change of the basal HPA axis activity. BDNF siRNA rats exhibited decreased BDNF levels and concomitant altered adrenocortoctrophic hormone (ACTH) and corticosterone responses to restraint stress, suggesting the involvement of BDNF in the HPA axis adaptive response to stress. In KD mice, BDNF levels in the hippocampus and hypothalamus were decreased by 20% in heterozygous and by 60% in homozygous animals compared to wild-type littermates. Although, in heterozygous KD mice, no significant change was observed in the basal levels of plasma ACTH and corticosterone, both hormones were significantly increased in homozygous KD mice, demonstrating that robust cerebral BDNF inhibition (60%) is necessary to affect basal HPA axis activity. All of these results in both rats and mice demonstrate the involvement and importance of a robust endogenous pool of BDNF in basal HPA axis regulation and the pivotal function of de novo BDNF synthesis in the establishment of an adapted response to stress. © 2015 British Society for Neuroendocrinology.

The effects of stress on hypothalamic-pituitary-adrenal (HPA) axis function in subjects with schizophrenia

NARCIS (Netherlands)

P.C. Guest (Paul); D. Martins-de-Souza (Daniel); H. Rahmoune (Hassan); S. Bahn (Sabine); P.C. Guest (Paul)

2013-01-01

textabstractOver the last few decades, evidence has been emerging that the pathogenesis of psychiatric disorders such as schizophrenia can involve perturbations of the hypothalamic-pituitary-adrenal (HPA) axis. Variations in the manifestation of these effects could be related to the differences in

Seismicity and state of stress near the Japan Trench axis off Miyagi, northeast Japan, after the 2011 Tohoku-Oki earthquake

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Obana, K.; Kodaira, S.; Takahashi, T.; Yamamoto, Y.; Nakamura, Y.; No, T.; Fujie, G.; Hino, R.; Shinohara, M.

2013-12-01

The 2011 Tohoku-Oki earthquake ruptured roughly 200 km wide and 500 km long megathrust along the Japan Trench. The rupture propagated to the trench axis with a maximum slip about 50 m near the trench axis. As a consequence of this large near-trench slip, earthquakes have been activated near the axis of the Japan Trench off Miyagi, northeast Japan. We have conducted ocean bottom seismograph (OBS) experiments in the Japan Trench axis area, surrounding area of the IODP JFAST drilling site, since the occurrence of the 2011 Tohoku-Oki earthquake. Although conventionally used OBS cannot be deployed at seafloor deeper than 6000 m water depth, we used newly developed ultra-deep OBS using ceramic sphere, which can be deployed at a depth of 9000 m, for the observations in the trench axis. The ultra-deep OBS has almost equivalent dimensions and weight with the conventionally used OBS, thus we can handle it in the same manner with the conventionally OBS without any special operation. As a result of a series of the OBS observations, we obtained accurate hypocenter locations and focal mechanisms in both seaward and landward of the trench axis. Earthquakes near the trench axis area were located within the overriding and incoming/subducting plates with very few on the plate interface below the inner trench slope landward of the trench axis. Most of the earthquakes both in the overriding and incoming/subducting plates having normal or strike-slip faulting focal mechanisms with T-axis normal to the trench axis. This indicates that tensional stress is dominant in the trench axis area. However, most seaward part of the seismicity within the overriding plate is characterized by a localized cluster of trench-normal compressional earthquakes, which may relate to spatial variation of the frictional behavior of the shallowest part of the megathrust. On the other hand, trench-normal extensional earthquakes in the incoming/subducting Pacific plate were located at depths shallower than about

Saikosaponin D relieves unpredictable chronic mild stress induced depressive-like behavior in rats: involvement of HPA axis and hippocampal neurogenesis.

Science.gov (United States)

Li, Hong-Yan; Zhao, Ying-Hua; Zeng, Min-Jie; Fang, Fang; Li, Min; Qin, Ting-Ting; Ye, Lu-Yu; Li, Hong-Wei; Qu, Rong; Ma, Shi-Ping

2017-11-01

Saikosaponin D (SSD), a major bioactive component isolated from Radix Bupleuri, has been reported to exert neuroprotective properties. The present study was designed to investigate the anti-depressant-like effects and the potential mechanisms of SSD. Behavioural tests including sucrose preference test (SPT), open field test (OFT) and forced swim test (FST) were performed to study the antidepressant-like effects of SSD. In addition, we examined corticosterone and glucocorticoid receptor (GR) levels to evaluate hypothalamic-pituitary-adrenal (HPA) axis function. Furthermore, hippocampal neurogenesis was assessed by testing doublecortin (DCX) levels, and neurotrophic molecule levels were also investigated in the hippocampus of rats. We found that unpredictable chronic mild stress (UCMS) rats displayed lost body weight, decreased sucrose consumption in SPT, reduced locomotive activity in OFT, and increased immobility time in FST. Chronic treatment with SSD (0.75, 1.50 mg/kg) remarkably ameliorated the behavioral deficiency induced by UCMS procedure. SSD administration downregulated elevated serum corticosterone levels, as well as alleviated the suppression of GR expression and nuclear translocation caused by UCMS, suggesting that SSD is able to remit the dysfunction of HPA axis. In addition, Western blot and immunohistochemistry analysis showed that SSD treatment significantly increased the generation of neurons in the hippocampus of UCMS rats indicated by elevated DCX levels. Moreover, hippocampal neurotrophic molecule levels of UCMS rats such as phosphorylated cAMP response element binding protein (p-CREB) and brain-derived neurotrophic factor (BDNF) were raised after SSD treatment. Together, Our results suggest that SSD opposed UCMS-induced depressive behaviors in rats, which was mediated, partially, by the enhancement of HPA axis function and consolidation of hippocampal neurogenesis.

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.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress

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Tsuru J

2014-11-01

Full Text Available Jusen Tsuru,1 Yoshihiro Tanaka,1 Yoshinobu Ishitobi,1 Yoshihiro Maruyama,1 Ayako Inoue,1 Aimi Kawano,1 Rie Ikeda,1 Tomoko Ando,1 Harumi Oshita,2 Saeko Aizawa,1 Koji Masuda,1 Haruka Higuma,1 Masayuki Kanehisa,1 Taiga Ninomiya,1 Jotaro Akiyoshi1 1Department of Neuropsychiatry, 2Department of Applied Linguistics, Faculty of Medicine, Oita University, Oita, Japan Background: Decreased expression of brain-derived neurotrophic factor (BDNF is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder.Methods: To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men using a social stress procedure (Trier Social Stress Test [TSST] and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A.Results: A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; P<0.05 was demonstrated that revealed different salivary cortisol responses in the TSST but not in electrical stimulation. Met/Met women had stronger cortisol responses than Val/Met and Val/Val individuals in the TSST. Met/Met men exhibited stronger salivary cortisol responses than Val/Met and Val/Val individuals in the TSST.Conclusion: These results indicate that a common, functionally significant polymorphism in BDNF had different effects on hypothalamic–pituitary–adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests. Keywords: stress, brain-derived neurotrophic factor, cortisol, saliva

Deposition of stress free c-axis oriented LiNbO3 thin film grown on (002) ZnO coated Si substrate

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Shandilya, Swati; Gupta, Vinay; Tomar, Monika

2012-01-01

C-axis oriented lithium niobate thin films have been deposited on Si substrate using RF sputtering technique. A thin buffer layer of c-axis (002) oriented ZnO on Si substrate has been used as a nucleating layer to promote the growth of (006) oriented LiNbO 3 film. The processing gas composition and pressure are found to be very critical in obtaining stress free LiNbO 3 film having desired (006) orientation. The LiNbO 3 films deposited under unique combination of sputtering pressure (10 mTorr) and argon percentage (80%) in reactive gas (Ar + O 2 ) composition become almost stress free having lattice parameter (1.3867 A) close to the bulk value. The observed variation in the structural properties and optical phonon modes observed by Raman spectroscopic studies of the oriented LiNbO 3 thin film with stress has been correlated with growth kinetics.

Imidazoline2 (I2) receptor- and alpha2-adrenoceptor-mediated modulation of hypothalamic-pituitary-adrenal axis activity in control and acute restraint stressed rats.

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Finn, David P; Hudson, Alan L; Kinoshita, Hiroshi; Coventry, Toni L; Jessop, David S; Nutt, David J; Harbuz, Michael S

2004-03-01

Central noradrenaline regulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis and the neuroendocrine response to stress. alpha2-adrenoceptors and imidazoline2 (I2) receptors modulate the activity of the central noradrenergic system. The present set of experiments investigated the role of alpha2-adrenoceptors and I2 receptors in the regulation of HPA axis activity under basal conditions and during exposure to the acute psychological stress of restraint. Three separate experiments were carried out in which rats were given an i.p. injection of either saline vehicle, the combined alpha2-adrenoceptor antagonist and I2 receptor ligand idazoxan (10 mg/kg), the selective I2 receptor ligand BU224 (2.5 or 10 mg/kg) or the selective alpha2-adrenoceptor antagonist RX821002 (2.5 mg/kg) with or without restraint stress. Drugs were administered immediately prior to restraint of 60 min duration. Blood was sampled pre-injection, 30, 60 and 240 min post-injection and plasma corticosterone was measured by radioimmunoassay. In experiment 1, idazoxan increased plasma corticosterone levels in naive animals and potentiated the corticosterone response to acute restraint stress. In experiment 2, BU224 administration increased plasma corticosterone levels in a dose-related manner in naive rats. The results of experiment 3 indicated that RX821002 also elevated plasma corticosterone levels in naive rats, however, only BU224 potentiated the corticosterone response to restraint stress. These studies suggest that both alpha2-adrenoceptors and I2 receptors play a role in modulating basal HPA axis activity and that I2 receptors may play a more important role than alpha2-adrenoceptors in modulating the HPA axis response to the acute psychological stress of restraint.

Corticosterone response to gestational stress and postpartum memory function in mice.

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Jafari, Zahra; Mehla, Jogender; Afrashteh, Navvab; Kolb, Bryan E; Mohajerani, Majid H

2017-01-01

Maternal stress is a common adversity during pregnancy. Gestational corticosterone alternations are thought to contribute to the etiology of postpartum behavioral disturbances. However, the impact of stress during pregnancy, in particular noise exposure, on gestational corticosterone fluctuations and spatial cognition in postpartum mice has not been fully understood yet. We hypothesized that noise exposure during pregnancy negatively affects gestational corticosterone levels and postpartum memory function in the dams similar to the physical stressors. Pregnant C57BL/6 mice were randomly assigned to either one of two stress conditions or a control condition. The noise stress (NS) was induced by presenting a loud intermittent 3000 Hz frequency on gestational days (GDs) 12, 14, and 16 for 24 hours, whereas the physical stress (PS) consisted of restraint and exposure to an elevated platform on GDs 12-16. Plasma corticosterone level was collected on GDs 11 and 17, and Morris water task (MWT) was carried out 30 days after parturition. Compared to the control group, the level of corticosterone in the stressed groups was significantly increased on GD17 relative to GD11. Significantly longer swim time and lower swim speed were observed in both stressed groups relative to the control group. Probe time was significantly shorter in the NS group than the other groups. The delta corticosterone level was significantly correlated with the swim time as well as the probe time in the three groups. Given the results, the adverse effects of gestational noise exposure on the hypothalamic pituitary-adrenal (HPA) axis activation and postpartum spatial learning and memory function were as large as/ or a bit stronger than the physical stresses. The findings suggest the significance of conservation against loud noise exposure in daily living, as well as need to further notice to the different aspects of gestational stress in mothers' behavior like offspring.

Beyond the HPA-axis: The role of the gonadal steroid hormone receptors in modulating stress-related responses in an animal model of PTSD.

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Fenchel, Daphna; Levkovitz, Yechiel; Vainer, Ella; Kaplan, Zeev; Zohar, Joseph; Cohen, Hagit

2015-06-01

The hypothalamic-pituitary-adrenal (HPA) axis, which plays a major role in the response to stress, and the hypothalamic-pituitary-gonadal (HPG) axis are closely linked with the ability to inhibit the other. Testosterone, a product of the HPG, has many beneficial effects beyond its functions as a sex hormone including anti-anxiety properties. In this study we examined the effect of stress exposure on gonadal hormones, and their efficacy in modulating anxiety-like response in an animal model of PTSD. Male rats were exposed to predator scent stress, followed by analysis of brain expression of androgen receptor (AR) receptor and estrogen receptor α (ERα). The behavioral effects of immediate treatment with testosterone, testosterone receptor antagonist (flutamide) or vehicle were evaluated using the elevated plus-maze, acoustic startle response and trauma-cue response. Levels of circulating corticosterone and testosterone were also measured after treatment. The behavioral effects of delayed testosterone treatment were explored in the same manner. We report that animals whose behavior was extremely disrupted (EBR) selectively displayed significant down-regulation of AR and ERα in the hippocampus. Immediate treatment with flutamide or delayed treatment with testosterone significantly increased prevalence rates of minimal behavioral response (MBR) and decreased prevalence of EBR with favorable behavioral results. Testosterone levels were higher in control un-exposed animals, while corticosterone was higher in control exposed animals. This study suggests that gonadal steroid hormones are involved in the neurobiological response to predator scent stress and thus warrant further study as a potential therapeutic avenue for the treatment of anxiety-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

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Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

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

Regulation of the activins-follistatins-inhibins axis by energy status: Impact on reproductive function.

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Perakakis, Nikolaos; Upadhyay, Jagriti; Ghaly, Wael; Chen, Joyce; Chrysafi, Pavlina; Anastasilakis, Athanasios D; Mantzoros, Christos S

2018-05-09

We have previously demonstrated that the adipose tissue derived hormone leptin controls reproductive function by regulating the hypothalamic-pituitary-gonadal axis in response to energy deficiency. Here, we evaluate the activins-follistatins-inhibins (AFI) axis during acute (short-term fasting in healthy people) and chronic energy deficiency (women with hypothalamic amenorrhea due to strenuous exercise [HA]) and investigate their relation to leptin and reproductive function in healthy subjects and subjects with HA. The AFI axis was investigated in: a) A double-blinded study in healthy subjects having three randomly assigned admissions, each time for four days: in the isocaloric fed state, complete fasting with placebo treatment, complete fasting with leptin replacement, b) A case-control study comparing women with HA vs healthy controls, c) An open-label interventional study investigating leptin treatment in women with HA over a period of up to three months, d) A randomized interventional trial investigating leptin treatment vs placebo in women with HA for nine months. The circulating levels of activin A, activin B, follistatin and follistatin-like 3 change robustly in response to acute and chronic energy deficiency. Leptin replacement in acute energy deprivation does not affect the levels of these hormones suggesting an independent regulation by these two hormonal pathways. In chronic energy deficiency, leptin replacement restores only activin B levels, which are in turn associated with an increase in the number of dominant follicles. We demonstrate for the first time that the AFI axis is affected both by acute and chronic energy deficiency. Partial restoration of a component of the axis, i.e. activin B only, through leptin replacement is associated with improved reproductive function in women with HA. Copyright © 2018. Published by Elsevier Inc.

Hypothalamus-pituitary-thyroid axis activity and function of cardiac muscle in energy deficit

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Katarzyna Lachowicz

2017-12-01

Full Text Available Frequently repeated statement that energy restriction is a factor that improves cardiovascular system function seems to be not fully truth. Low energy intake modifies the hypothalamus-pituitary-thyroid axis activity and thyroid hormone peripheral metabolism. Thyroid hormones, as modulators of the expression and activity of many cardiomyocyte proteins, control heart function. Decreased thyroid hormone levels and their disturbanced conversion and action result in alternation of cardiac remodeling, disorder of calcium homeostasis and diminish myocardial contractility. This review provides a summary of the current state of knowledge about the mechanisms of energy restriction effects on thyroidal axis activity, thyroid hormone peripheral metabolism and action in target tissues, especially in cardiac myocytes. We also showed the existence of energy restriction-thyroid-heart pathway.

The hypothalamic-pituitary-adrenal axis: what can it tell us about stressors?

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Armario, Antonio

2006-10-01

The hypothalamic-pituitary-adrenal (HPA) axis is an extremely sensitive physiological system whose activation, with the consequent release of ACTH and glucocorticoids, is triggered by a wide range of psychological experiences and physiological perturbations (stressors). The HPA axis is also activated by a high number of pharmacological agents that markedly differ in structure and function, although the precise mechanisms remain in most cases unknown. Activation of the HPA axis is the consequence of the convergence of stimulatory inputs from different brain regions into the paraventricular nucleus of the hypothalamus (PVN), where the most important ACTH secretagogues (corticotrophin releasing factor, CRF, and arginin-vasopressin, AVP) are formed. Plasma levels of ACTH and corticosterone (the latter under more restricted conditions), are considered as good markers of stress for three main reasons: (a) their plasma levels are proportional to the intensity of emotional and systemic stressors, (b) daily repeated exposure to a stressor usually resulted in reduced ACTH response to the same stressor, that is termed adaptation or habituation; and (c) chronic exposure to stressful situations results in tonic changes in the HPA axis that can be used as indices of the accumulative impact of these situations. These changes can be evaluated under resting conditions (i.e. adrenal weight, CRF and AVP gene expression in the PVN) or after some challenges (administration of CRF, ACTH or dexamethasone) that are classical endocrinological tests. There is also evidence that the activation of the HPA axis may also reflect subtle changes in the characteristics of the stressful situations (unpredictability, lack of control, omission of expected rewards, presence of conspecifics), although this is a topic that requires further studies.

Microbiota Modulate Anxiety-Like Behavior and Endocrine Abnormalities in Hypothalamic-Pituitary-Adrenal Axis

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Ran Huo

2017-11-01

Full Text Available Intestinal microbes are an important system in the human body, with significant effects on behavior. An increasing body of research indicates that intestinal microbes affect brain function and neurogenesis, including sensitivity to stress. To investigate the effects of microbial colonization on behavior, we examined behavioral changes associated with hormones and hormone receptors in the hypothalamic-pituitary-adrenal (HPA axis under stress. We tested germ-free (GF mice and specific pathogen-free (SPF mice, divided into four groups. A chronic restraint stress (CRS protocol was utilized to induce external pressure in two stress groups by restraining mice in a conical centrifuge tube for 4 h per day for 21 days. After CRS, Initially, GF restraint-stressed mice explored more time than SPF restraint-stressed mice in the center and total distance of the OFT. Moreover, the CRH, ACTH, CORT, and ALD levels in HPA axis of GF restraint-stressed mice exhibited a significantly greater increase than those of SPF restraint-stressed mice. Finally, the Crhr1 mRNA levels of GF CRS mice were increased compared with SPF CRS mice. However, the Nr3c2 mRNA levels of GF CRS mice were decreased compared with SPF CRS mice. All results revealed that SPF mice exhibited more anxiety-like behavior than GF mice under the same external stress. Moreover, we also found that GF mice exhibited significant differences in, hormones, and hormone receptors compared with SPF mice. In conclusion, Imbalances of the HPA axis caused by intestinal microbes could affect the neuroendocrine system in the brain, resulting in an anxiety-like behavioral phenotype. This study suggested that intervention into intestinal microflora may provide a new approach for treating stress-related diseases.

Association of BDNF Val66Met polymorphism with HPA and SAM axis reactivity to psychological and physical stress.

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Tsuru, Jusen; Tanaka, Yoshihiro; Ishitobi, Yoshinobu; Maruyama, Yoshihiro; Inoue, Ayako; Kawano, Aimi; Ikeda, Rie; Ando, Tomoko; Oshita, Harumi; Aizawa, Saeko; Masuda, Koji; Higuma, Haruka; Kanehisa, Masayuki; Ninomiya, Taiga; Akiyoshi, Jotaro

2014-01-01

Decreased expression of brain-derived neurotrophic factor (BDNF) is implicated in enhanced stress responses. The BDNF Val66Met polymorphism is associated with psychological changes; for example, carriers of the Met allele exhibit increased harm avoidance as well as a higher prevalence of depression and anxiety disorder. To analyze the effects of BDNF Val66Met on stress responses, we tested 226 university students (88 women and 138 men) using a social stress procedure (Trier Social Stress Test [TSST]) and an electrical stimulation stress test. Stress indices were derived from repeated measurements of salivary α-amylase, salivary cortisol, heart rate, and psychological testing during the stress tests. All subjects were genotyped for the Val66Met polymorphism (G196A). A significant three-way interaction (time [3 levels] × BDNF [Val/Val, Val/Met, Met/Met]; PBDNF had different effects on hypothalamic-pituitary-adrenocortical axis reactivity but not on sympathetic adrenomedullary reactivity in TSST and electrical stimulation tests.

Perspectives on stress resilience and adolescent neurobehavioral function.

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Romeo, Russell D

2015-01-01

Interest in adolescence as a crucial stage of neurobehavioral maturation is growing, as is the concern of how stress may perturb this critical period of development. Though it is well recognized that stress-related vulnerabilities increase during adolescence, not all adolescent individuals are uniformly affected by stress nor do stressful experiences inevitability lead to negative outcomes. Indeed, many adolescents show resilience to stress-induced dysfunctions. However, relatively little is known regarding the mechanisms that may mediate resilience to stress in adolescence. The goal of this brief review is to bring together a few separate, yet related lines of research that highlight specific variables that may influence stress resilience during adolescence, including early life programming of the hypothalamic-pituitary-adrenal (HPA) axis, stress inoculation, and genetic predisposition. Though we are far from a clear understanding of the factors that mediate resistance to stress-induced dysfunctions, it is imperative that we identify and delineate these aspects of resilience to help adolescents reach their full potential, even in the face of adversity.

Perspectives on stress resilience and adolescent neurobehavioral function

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Russell D. Romeo

2015-01-01

Full Text Available Interest in adolescence as a crucial stage of neurobehavioral maturation is growing, as is the concern of how stress may perturb this critical period of development. Though it is well recognized that stress-related vulnerabilities increase during adolescence, not all adolescent individuals are uniformly affected by stress nor do stressful experiences inevitability lead to negative outcomes. Indeed, many adolescents show resilience to stress-induced dysfunctions. However, relatively little is known regarding the mechanisms that may mediate resilience to stress in adolescence. The goal of this brief review is to bring together a few separate, yet related lines of research that highlight specific variables that may influence stress resilience during adolescence, including early life programming of the hypothalamic-pituitary-adrenal (HPA axis, stress inoculation, and genetic predisposition. Though we are far from a clear understanding of the factors that mediate resistance to stress-induced dysfunctions, it is imperative that we identify and delineate these aspects of resilience to help adolescents reach their full potential, even in the face of adversity.

The influence of surgical stress on the psychoneuro-endocrine-immune axis.

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Dahanukar S

1996-01-01

Full Text Available Stress is known to depress the immune system severely. This study was done to evaluate whether surgical stress influenced polymorphonuclear (PMN and monocyte functions in association with serum cortisol and the anxiety score as measured on the HARS Rating Scale. We found that surgery (irrespective of whether it was major or minor significantly depressed PMN and monocyte functions and increased serum cortisol levels. PMN phagocytosis correlated significantly (p < 0.05 with the rise in serum cortisol. In spite of these changes, postoperative clinical recovery was uneventful. No major alterations in the HARS scores were noted pre and post operatively. This study demonstrates that surgical stress depresses the immune system with a concomitant rise in cortisol.

Tiam1/Vav2-Rac1 axis: A tug-of-war between islet function and dysfunction.

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Kowluru, Anjaneyulu

2017-05-15

Glucose-stimulated insulin secretion [GSIS] from the islet β-cell involves a well-orchestrated interplay between metabolic and cationic events. It is well established that intracellular generation of adenine and guanine nucleotide triphosphates [e.g., ATP and GTP] represents one of the requisite signaling steps in GSIS. The small molecular mass GTP-binding proteins [G-proteins; e.g., Rac1 and Cdc42] have been shown to regulate islet β-cell function including actin cytoskeletal remodeling and fusion of insulin granules with the plasma membrane for GSIS to occur. In this context, several regulatory factors for these G-proteins have been identified in the pancreatic β-cell; these include guanine nucleotide exchange factors [GEFs] and guanine nucleotide dissociation inhibitors [GDI]. Recent pharmacological and molecular biological evidence identified Tiam1 and Vav2 as GEFs for Rac1 in promoting physiological insulin secretion. Paradoxically, emerging evidence in multiple cell types, including the islet β-cell, suggests key roles for Rac1 in the onset of cellular dysfunction under conditions of metabolic stress and diabetes. Furthermore, functional inactivation of either Tiam1 or Vav2 appears to attenuate sustained activation of Rac1 and its downstream signaling events [activation of stress kinases] under conditions of metabolic stress. Together, these findings suggest both "friendly" and "non-friendly" roles for Tiam1/Vav2-Rac1 signaling axis in islet β-cell in health and diabetes. Our current understanding of the field and the knowledge gaps that exist in this area of islet biology are heighted herein. Furthermore, potential caveats in the specificity and selectivity of pharmacological inhibitors that are available currently are discussed in this Commentary. Published by Elsevier Inc.

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

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

2015-01-01

The purpose of the present study was to investigate the associations between personality facets and hypothalamic-pituitary-adrenal (HPA) axis functioning. Previous studies have mainly focussed on stress-induced HPA-axis activation. We hypothesized that other characteristics of HPA-axis functioning would have a stronger association with personality based on the neuroendocrine literature. Data (n=343) were used from the TRacking Adolescents' Individual Lives Survey (TRAILS), a large prospective...

The involvement of the hypothalamopituitary-adrenocortical axis in stress physiology and its significance in the assessment of animal welfare in cattle

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Emma J. Brown

2017-04-01

Full Text Available The intensification of cattle production has raised concern for animal welfare due to the stress that is associated with farming practices. The welfare of an animal is determined by the animal’s ability to cope with or adapt to its continuously changing environment and the biological cost that is associated with this adaptation and maintenance. Stressors arise from various psychological, physiological and physical aspects of farming practices due to management and human–cattle interactions. Measuring the activity of the hypothalamopituitary-adrenocortical (HPA axis with plasma cortisol levels is a useful method for determining the effects of stress on animals as it is stimulated at the onset of a perceived stress. The activation of the HPA axis affects various target tissues or systems and can result in suppression of the immune system, increased susceptibility to disease and adverse effects on reproductive success in prenatal and neonatal calves. Although some levels of stress associated with farming practices are unavoidable, improvements in farming methods need to be implemented in order to maintain or increase the efficiency of cattle production in a way that does not compromise the welfare of the animal.

Salubrious effects of oxytocin on social stress-induced deficits

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Smith, Adam S.; Wang, Zuoxin

2011-01-01

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

Eating behaviour and stress: a pathway to obesity

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Sarah J Spencer

2014-05-01

Full Text Available Stress causes or contributes to a huge variety of diseases and disorders. Recent evidence suggests obesity and other eating-related disorders may be among these. Immediately after a stressful event is experienced, there is a corticotropin-releasing-hormone (CRH-mediated suppression of food intake. This diverts the body’s resources away from the less pressing need to find and consume food, prioritizing fight, flight, or withdrawal behaviours so the stressful event can be dealt with. In the hours following this, however, there is a glucocorticoid-mediated stimulation of hunger and eating behaviour. In the case of an acute stress that requires a physical response, such as a predator-prey interaction, this hypothalamic-pituitary-adrenal (HPA axis modulation of food intake allows the stressful event to be dealt with and the energy used to be replaced afterwards. In the case of ongoing psychological stress, however, chronically elevated glucocorticoids can lead to chronically stimulated eating behaviour and excessive weight gain. In particular, stress can enhance the propensity to eat high calorie palatable food via its interaction with central reward pathways. Activation of this circuitry can also interact with the HPA axis to suppress its further activation, meaning not only can stress encourage eating behaviour, but eating can suppress the HPA axis and the feeling of stress. In this review we will explore the theme of eating behaviour and stress and how these can modulate one another. We will address the interactions between the HPA axis and eating, introducing a potential integrative role for the orexigenic hormone, ghrelin. We will also examine early life and epigenetic modulation of the HPA axis and how this can influence eating behaviour. Finally, we will investigate the clinical implications of changes to HPA axis function and how this may be contributing to obesity in our society.

On the generation of short-axis and radial long-axis slices in thallium-201 myocardial perfusion single-photon emission tomography

International Nuclear Information System (INIS)

Hastenberg, R.P.J.M. van; Eindhoven Univ. of Technology; Kemernik, G.J.; Hasman, A.

1996-01-01

We tried to develop fully automatic reorientation algorithms in thallium-201 myocardial perfusion single-photon emission tomography, and tested a method to evaluate the quality of reorientation. The left ventricle was automatically segmented using count density information, contours generated with Laplacian operators in both transaxial and sagittal slices, and morphological and positional characteristics of the contours. Reorientation was automatically performed based on knowledge of the long axis of a second degree surface fitted to the myocardial wall. We tried to achieve improvement in reorientation without relying on any functional description of left ventricular shape. Quality of reorientation was evaluated and improved using interactive tools in combination with radial long-axis slices. Two groups of 50 patients, after stress and rest, were analysed using the traditional manual and the fully automatic procedures. Automatic segmentation was successful in 98 out of 100 cases, and automatic reorientation was of reasonable quality. Reorientation obtained with the radial long-axis slices tool was better than after traditional manual or automatic reorientation. Automatic reorientation based on second degree surface fitting was in our hands less successful than reported in the literature. The tool using radial long-axis slices provides a better standard for testing reorientation algorithms than the traditional manual method. (orig.)

The stress-buffering effect of acute exercise: Evidence for HPA axis negative feedback.

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Zschucke, Elisabeth; Renneberg, Babette; Dimeo, Fernando; Wüstenberg, Torsten; Ströhle, Andreas

2015-01-01

According to the cross-stressor adaptation hypothesis, physically trained individuals show lower physiological and psychological responses to stressors other than exercise, e.g. psychosocial stress. Reduced stress reactivity may constitute a mechanism of action for the beneficial effects of exercise in maintaining mental health. With regard to neural and psychoneuroendocrine stress responses, the acute stress-buffering effects of exercise have not been investigated yet. A sample of highly trained (HT) and sedentary (SED) young men was randomized to either exercise on a treadmill at moderate intensity (60-70% VO2max; AER) for 30 min, or to perform 30 min of "placebo" exercise (PLAC). 90 min later, an fMRI experiment was conducted using an adapted version of the Montreal Imaging Stress Task (MIST). The subjective and psychoneuroendocrine (cortisol and α-amylase) changes induced by the exercise intervention and the MIST were assessed, as well as neural activations during the MIST. Finally, associations between the different stress responses were analysed. Participants of the AER group showed a significantly reduced cortisol response to the MIST, which was inversely related to the previous exercise-induced α-amylase and cortisol fluctuations. With regard to the sustained BOLD signal, we found higher bilateral hippocampus (Hipp) activity and lower prefrontal cortex (PFC) activity in the AER group. Participants with a higher aerobic fitness showed lower cortisol responses to the MIST. As the Hipp and PFC are brain structures prominently involved in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis, these findings indicate that the acute stress-buffering effect of exercise relies on negative feedback mechanisms. Positive affective changes after exercise appear as important moderators largely accounting for the effects related to physical fitness. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-term effects of early parental loss due to divorce on the HPA axis.

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Bloch, Miki; Peleg, Ido; Koren, Danny; Aner, Hamotal; Klein, Ehud

2007-04-01

We investigated the long-term effects of divorce and early separation from one parent on HPA axis reactivity, in young adults without psychopathology. Participants were 44 young subjects, 22 whose parents divorced before they reached age 10, and 22 controls. Psychiatric symptomatology was measured with the Brief Symptom Inventory (BSI), family perceived stress by the Dyadic Adjustment Scale (DAS), and bonding by the Parental Bonding Instrument (PBI). Assessment of HPA axis function included baseline morning cortisol and ACTH and cortisol response to a CRH stimulation test. No baseline or stimulated group differences were observed for ACTH. Cortisol levels were consistently but insignificantly lower in the divorce group throughout the CRH stimulation reaching statistical significance only at 5 min (p<0.03). Group by time effect reached a trend level (p<0.06). A correlation was found between psychiatric symptomatology and PBI scores; however, both parameters did not correlate with HPA axis activity. A significant correlation was found between DAS scores and ACTH. A regression model revealed a contributing effect for both family stress and child-parent bonding to stimulated ACTH levels. These preliminary findings suggest that even in the absence of adult psychopathology, a history of childhood separation from one parent due to divorce may lead to detectable, albeit mild, long-term alterations in HPA axis activity. Furthermore, they suggest that level of stress at home and parental bonding are important determinants of this effect. It is likely that divorce has significant and sustained effects on children's HPA axis only in the context of a traumatic separation.

Deposition of stress free c-axis oriented LiNbO{sub 3} thin film grown on (002) ZnO coated Si substrate

Energy Technology Data Exchange (ETDEWEB)

Shandilya, Swati; Gupta, Vinay [Department of Physics and Astrophysics, University of Delhi, Delhi 110007 (India); Tomar, Monika [Miranda House, University of Delhi, Delhi 110007 (India)

2012-05-15

C-axis oriented lithium niobate thin films have been deposited on Si substrate using RF sputtering technique. A thin buffer layer of c-axis (002) oriented ZnO on Si substrate has been used as a nucleating layer to promote the growth of (006) oriented LiNbO{sub 3} film. The processing gas composition and pressure are found to be very critical in obtaining stress free LiNbO{sub 3} film having desired (006) orientation. The LiNbO{sub 3} films deposited under unique combination of sputtering pressure (10 mTorr) and argon percentage (80%) in reactive gas (Ar + O{sub 2}) composition become almost stress free having lattice parameter (1.3867 A) close to the bulk value. The observed variation in the structural properties and optical phonon modes observed by Raman spectroscopic studies of the oriented LiNbO{sub 3} thin film with stress has been correlated with growth kinetics.

Cannabinoids and glucocorticoids modulate emotional memory after stress.

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Akirav, Irit

2013-12-01

Bidirectional and functional relationships between glucocorticoids and the endocannabinoid system have been demonstrated. Here, I review the interaction between the endocannabinoid and glucocorticoid/stress systems. Specifically, stress is known to produce rapid changes in endocannabinoid signaling in stress-responsive brain regions. In turn, the endocannabinoid system plays an important role in the downregulation and habituation of hypothalamic-pituitary-adrenocortical (HPA) axis activity in response to stress. Glucocorticoids also recruit the endocannabinoid system to exert rapid negative feedback control of the HPA axis during stress. It became increasingly clear, however, that cannabinoid CB1 receptors are also abundantly expressed in the basolateral amygdala (BLA) and other limbic regions where they modulate emotional arousal effects on memory. Enhancing cannabinoids signaling using exogenous CB1 receptor agonists prevent the effects of acute stress on emotional memory. I propose a model suggesting that the ameliorating effects of exogenously administered cannabinoids on emotional learning after acute stress are mediated by the decrease in the activity of the HPA axis via GABAergic mechanisms in the amygdala. Copyright © 2013 Elsevier Ltd. All rights reserved.

Metabolomics analysis identifies sex-associated metabotypes of oxidative stress and the autotaxin–lysoPA axis in COPD

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Naz, Shama; Kolmert, Johan; Yang, Mingxing; Reinke, Stacey N.; Kamleh, Muhammad Anas; Snowden, Stuart; Heyder, Tina; Levänen, Bettina; Erle, David J.; Sköld, C. Magnus; Wheelock, Åsa M.; Wheelock, Craig E.

2017-01-01

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease and a leading cause of mortality and morbidity worldwide. The aim of this study was to investigate the sex dependency of circulating metabolic profiles in COPD. Serum from healthy never-smokers (healthy), smokers with normal lung function (smokers), and smokers with COPD (COPD; Global Initiative for Chronic Obstructive Lung Disease stages I–II/A–B) from the Karolinska COSMIC cohort (n=116) was analysed using our nontargeted liquid chromatography–high resolution mass spectrometry metabolomics platform. Pathway analyses revealed that several altered metabolites are involved in oxidative stress. Supervised multivariate modelling showed significant classification of smokers from COPD (p=2.8×10−7). Sex stratification indicated that the separation was driven by females (p=2.4×10−7) relative to males (p=4.0×10−4). Significantly altered metabolites were confirmed quantitatively using targeted metabolomics. Multivariate modelling of targeted metabolomics data confirmed enhanced metabolic dysregulation in females with COPD (p=3.0×10−3) relative to males (p=0.10). The autotaxin products lysoPA (16:0) and lysoPA (18:2) correlated with lung function (forced expiratory volume in 1 s) in males with COPD (r=0.86; pCOPD, and suggest that sex-enhanced dysregulation in oxidative stress, and potentially the autotaxin–lysoPA axis, are associated with disease mechanisms and/or prevalence. PMID:28642310

Design of a multi-axis implantable MEMS sensor for intraosseous bone stress monitoring

International Nuclear Information System (INIS)

Alfaro, Fernando; Weiss, Lee; Campbell, Phil; Fedder, Gary K; Miller, Mark

2009-01-01

The capability to assess the biomechanical properties of living bone is important for basic research as well as the clinical management of skeletal trauma and disease. Even though radiodensitometric imaging is commonly used to infer bone quality, bone strength does not necessarily correlate well with these non-invasive measurements. This paper reports on the design, fabrication and initial testing of an implantable ultra-miniature multi-axis sensor for directly measuring bone stresses at a micro-scale. The device, which is fabricated with CMOS-MEMS processes, is intended to be permanently implanted within open fractures, or embedded in bone grafts, or placed on implants at the interfaces between bone and prosthetics. The stress sensor comprises an array of piezoresistive pixels to detect a stress tensor at the interfacial area between the MEMS chip and bone, with a resolution to 100 Pa, in 1 s averaging. The sensor system design and manufacture is also compatible with the integration of wireless RF telemetry, for power and data retrieval, all within a 3 mm × 3 mm × 0.3 mm footprint. The piezoresistive elements are integrated within a textured surface to enhance sensor integration with bone. Finite element analysis led to a sensor design for normal and shear stress detection. A wired sensor was fabricated in the Jazz 0.35 µm BiCMOS process and then embedded in mock bone material to characterize its response to tensile and bending loads up to 250 kPa

Psychostimulants and forced swim stress interaction: how activation of the hypothalamic-pituitary-adrenal axis and stress-induced hyperglycemia are affected.

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Gagliano, Humberto; Ortega-Sanchez, Juan Antonio; Nadal, Roser; Armario, Antonio

2017-10-01

We recently reported that simultaneous exposure to amphetamine and various stressors resulted in reduced hypothalamic-pituitary-adrenal (HPA) and glycemic responses to the stressors. Since this is a new and relevant phenomenon, we wanted to further explore this interaction. This study aims (i) to characterize the effect of various doses of amphetamine on the physiological response to a predominantly emotional stressor (forced swim) when the drug was given immediately before stress; (ii) to study if an interaction appears when the drug was given 30 min or 7 days before swim; and (iii) to know whether cocaine causes similar effects when given just before stress. Adult male rats were used and plasma levels of ACTH, corticosterone, and glucose were the outcomes. Amphetamine caused a dose-dependent activation of the HPA axis, but all doses reduced HPA and glycemic responses to swim when given just before the stressor. Importantly, during the post-swim period, the stressor potently inhibited the ACTH response to amphetamine, demonstrating mutual inhibition between the two stimuli. The highest dose of amphetamine also reduced the response to swim when given 30 min before stress, whereas it caused HPA sensitization when given 7 days before. Cocaine also reduced stress-induced HPA activation when given just before swim. The present results demonstrate a negative synergy between psychostimulants (amphetamine and cocaine) and stress regarding HPA and glucose responses when rats were exposed simultaneously to both stimuli. The inhibitory effect of amphetamine is also observed when given shortly before stress, but not some days before.

Interindividual differences in stress sensitivity: basal and stress-induced cortisol levels differentially predict neural vigilance processing under stress.

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Henckens, Marloes J A G; Klumpers, Floris; Everaerd, Daphne; Kooijman, Sabine C; van Wingen, Guido A; Fernández, Guillén

2016-04-01

Stress exposure is known to precipitate psychological disorders. However, large differences exist in how individuals respond to stressful situations. A major marker for stress sensitivity is hypothalamus-pituitary-adrenal (HPA)-axis function. Here, we studied how interindividual variance in both basal cortisol levels and stress-induced cortisol responses predicts differences in neural vigilance processing during stress exposure. Implementing a randomized, counterbalanced, crossover design, 120 healthy male participants were exposed to a stress-induction and control procedure, followed by an emotional perception task (viewing fearful and happy faces) during fMRI scanning. Stress sensitivity was assessed using physiological (salivary cortisol levels) and psychological measures (trait questionnaires). High stress-induced cortisol responses were associated with increased stress sensitivity as assessed by psychological questionnaires, a stronger stress-induced increase in medial temporal activity and greater differential amygdala responses to fearful as opposed to happy faces under control conditions. In contrast, high basal cortisol levels were related to relative stress resilience as reflected by higher extraversion scores, a lower stress-induced increase in amygdala activity and enhanced differential processing of fearful compared with happy faces under stress. These findings seem to reflect a critical role for HPA-axis signaling in stress coping; higher basal levels indicate stress resilience, whereas higher cortisol responsivity to stress might facilitate recovery in those individuals prone to react sensitively to stress. © The Author (2015). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Predicting mental disorders from hypothalamic-pituitary-adrenal axis functioning: a 3-year follow-up in the TRAILS study.

Science.gov (United States)

Nederhof, E; van Oort, F V A; Bouma, E M C; Laceulle, O M; Oldehinkel, A J; Ormel, J

2015-08-01

Hypothalamic-pituitary-adrenal axis functioning, with cortisol as its major output hormone, has been presumed to play a key role in the development of psychopathology. Predicting affective disorders from diurnal cortisol levels has been inconclusive, whereas the predictive value of stress-induced cortisol concentrations has not been studied before. The aim of this study was to predict mental disorders over a 3-year follow-up from awakening and stress-induced cortisol concentrations. Data were used from 561 TRAILS (TRacking Adolescents' Individual Lives Survey) participants, a prospective cohort study of Dutch adolescents. Saliva samples were collected at awakening and half an hour later and during a social stress test at age 16. Mental disorders were assessed 3 years later with the Composite International Diagnostic Interview (CIDI). A lower cortisol awakening response (CAR) marginally significantly predicted new disorders [odds ratio (OR) 0.77, p = 0.06]. A flat recovery slope predicted disorders with a first onset after the experimental session (OR 1.27, p = 0.04). Recovery revealed smaller, non-significant ORs when predicting new onset affective or anxiety disorders, major depressive disorder, or dependence disorders in three separate models, corrected for all other new onsets. Our results suggest that delayed recovery and possibly reduced CAR are indicators of a more general risk status and may be part of a common pathway to psychopathology. Delayed recovery suggests that individuals at risk for mental disorders perceived the social stress test as less controllable and less predictable.

Effects of early childhood trauma on hypothalamic-pituitary-adrenal (HPA) axis function in patients with Chronic Fatigue Syndrome.

Science.gov (United States)

Kempke, Stefan; Luyten, Patrick; De Coninck, Sarah; Van Houdenhove, Boudewijn; Mayes, Linda C; Claes, Stephan

2015-02-01

There is a paucity of studies that have investigated the assumption that early childhood trauma is associated with hypothalamic-pituitary-adrenal (HPA) axis dysfunction in Chronic Fatigue Syndrome (CFS). The current study is the first to simultaneously investigate relationships among early childhood trauma, cortisol activity, and cortisol stress reactivity to psychosocial stress in a sample of well-screened CFS patients. We also examined whether self-critical perfectionism (SCP) plays a mediating role in the potential relationship between early trauma and neurobiological stress responses. A total of 40 female patients diagnosed with CFS were asked to provide morning saliva cortisol samples (after awakening, 30min later, and 1h later) for seven consecutive days as a measure of cortisol activity. In addition, patients were exposed to the Trier Social Stress Test, a well-validated stress test, to investigate the relationship between early childhood trauma and cortisol stress reactivity. Before the start of the study, patients completed the Childhood Trauma Questionnaire-Short form (CTQ-SF) as a measure of early childhood trauma (i.e. sexual, physical and emotional traumatic experiences). SCP was measured with the Depressive Experiences Questionnaire (DEQ). Data were analyzed by calculating several indices of cortisol secretion (i.e. Cortisol Awakening Response and Area Under the Curve). There was no association between early childhood trauma and cortisol as measured over the 7-day period. However, emotional neglect was significantly negatively related to cortisol reactivity in the TSST. SCP did not significantly mediate this association. Findings of this study suggest that emotional neglect is associated with blunted HPA axis reactivity, congruent with the assumption that CFS may reflect loss of adaptability of the neuroendocrine stress response system in at least a subgroup of patients. Copyright © 2014 Elsevier Ltd. All rights reserved.

Investigating the effect of acute sleep deprivation on hypothalamic-pituitary-adrenal-axis response to a psychosocial stressor.

Science.gov (United States)

Vargas, Ivan; Lopez-Duran, Nestor

2017-05-01

The hypothalamic-pituitary-adrenal (HPA) axis has been previously identified as one potential mechanism that may explain the link between sleep deprivation and negative health outcomes. However, few studies have examined the direct association between sleep deprivation and HPA-axis functioning, particularly in the context of stress. Therefore, the aim of the current study was to investigate the relationship between acute sleep deprivation and HPA-axis reactivity to a psychosocial stressor. Participants included 40 healthy, young adults between the ages of 18-29. The current protocol included spending two nights in the laboratory. After an adaptation night (night 1), participants were randomized into either a sleep deprivation condition (29 consecutive hours awake) or a control condition (night 2). Following the second night, all participants completed the Trier Social Stress Test (TSST). Salivary cortisol was collected before, during, and after the TSST. Results indicated that there were significant group differences in cortisol stress reactivity. Specifically, compared to participants in the control condition, participants in the sleep deprivation condition had greater baseline (i.e., pre-stress) cortisol, yet a blunted cortisol response to the TSST. Taken together, a combination of elevated baseline cortisol (and its subsequent effect on HPA-axis regulatory processes) and a relative 'ceiling' on the amount of cortisol a laboratory stressor can produce may explain why participants in the sleep deprivation condition demonstrated blunted cortisol responses. Copyright © 2017 Elsevier Ltd. All rights reserved.

Neuropsychological and hypothalamic-pituitary-axis function in female patients with melancholic and non-melancholic depression.

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Michopoulos, Ioannis; Zervas, Iannis M; Pantelis, Chris; Tsaltas, Eleftheria; Papakosta, Vassiliki-Maria; Boufidou, Fotini; Nikolaou, Chrissoula; Papageorgiou, Charalambos; Soldatos, Costas R; Lykouras, Lefteris

2008-06-01

Executive function deficits in depression implicate involvement of frontal-striatal circuits. However, studies of hypothalamic-pituitary-axis (HPA) function suggest that stress-related brain changes of hippocampus may also implicate prefrontal-hippocampal circuits, which may explain the profile of both executive dysfunction and memory deficits. In this study we examined the performance of patients with major depressive disorder (MDD) on tasks of memory and executive function in relation to melancholic features and to cortisol levels. Our hypothesis was that raised cortisol levels in melancholic patients would correlate with these deficits. Forty female MDD patients, 20 having melancholic features (MEL vs. Non-MEL), and 20 sex-age- and education-matched normal controls were investigated using the Cambridge neuropsychological test automated battery (CANTAB), to assess memory (paired associative learning, PAL; short-term recognition memory, SRM) and executive (intradimensional/extradimensional set-shifting, ID/ED; Stockings of Cambridge, SOC) functions. Plasma and salivary cortisol levels were measured. The MDD patients performed worse than controls on PAL and both executive tasks. The MEL group differed from controls on all tests, and differed from the non-MEL only at the ED stage of the ID/ED task. Patient cortisol levels were within the normal range and did not correlate with neuropsychological performance for any group. MDD patients showed neuropsychological deficits on tasks of executive function and memory, supporting the model of frontal-temporal dysfunction. MEL vs. non-MEL performed worse overall and demonstrated a qualitative difference in set shifting, perhaps implicating more extensive prefrontal involvement. Cortisol levels did not correlate with depression severity or the observed deficits.

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

Science.gov (United States)

Belda, Xavier; Nadal, Roser; Armario, Antonio

2016-08-11

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

Axi-symmetric generalized thermoelastic diffusion problem with two-temperature and initial stress under fractional order heat conduction

International Nuclear Information System (INIS)

Deswal, Sunita; Kalkal, Kapil Kumar; Sheoran, Sandeep Singh

2016-01-01

A mathematical model of fractional order two-temperature generalized thermoelasticity with diffusion and initial stress is proposed to analyze the transient wave phenomenon in an infinite thermoelastic half-space. The governing equations are derived in cylindrical coordinates for a two dimensional axi-symmetric problem. The analytical solution is procured by employing the Laplace and Hankel transforms for time and space variables respectively. The solutions are investigated in detail for a time dependent heat source. By using numerical inversion method of integral transforms, we obtain the solutions for displacement, stress, temperature and diffusion fields in physical domain. Computations are carried out for copper material and displayed graphically. The effect of fractional order parameter, two-temperature parameter, diffusion, initial stress and time on the different thermoelastic and diffusion fields is analyzed on the basis of analytical and numerical results. Some special cases have also been deduced from the present investigation.

Gradient COUP-TFI Expression Is Required for Functional Organization of the Hippocampal Septo-Temporal Longitudinal Axis.

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Flore, Gemma; Di Ruberto, Giuseppina; Parisot, Joséphine; Sannino, Sara; Russo, Fabio; Illingworth, Elizabeth A; Studer, Michèle; De Leonibus, Elvira

2017-02-01

The hippocampus (HP), a medial cortical structure, is subdivided into a distinct dorsal (septal) and ventral (temporal) portion, which is separated by an intermediate region lying on a longitudinal curvature. While the dorsal portion is more dedicated to spatial navigation and memory, the most ventral part processes emotional information. Genetic factors expressed in gradient during development seem to control the size and correct positioning of the HP along its longitudinal axis; however, their roles in regulating differential growth and in supporting its anatomical and functional dissociation remain unexplored. Here, we challenge the in vivo function of the nuclear receptor COUP-TFI (chicken ovalbumin upstream promoter transcription factor 1) in controlling the hippocampal, anatomical, and functional properties along its longitudinal axis. Loss of cortical COUP-TFI function results in a dysmorphic HP with altered shape, volume, and connectivity, particularly in its dorsal and intermediate regions. Notably, topographic inputs from the entorhinal cortex are strongly impaired in the dorsal portion of COUP-TFI mutants. These severe morphological changes are associated with selective spatial learning and memory impairment. These findings identify a novel transcriptional regulator required in the functional organization along the hippocampal septo-temporal axis supporting a genetic basis of the hippocampal volumetric growth with its final shape, circuit, and type of memory function. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Gut Microbiota-brain Axis

Institute of Scientific and Technical Information of China (English)

Hong-Xing Wang; Yu-Ping Wang

2016-01-01

Objective:To systematically review the updated information about the gut microbiota-brain axis.Data Sources:All articles about gut microbiota-brain axis published up to July 18,2016,were identified through a literature search on PubMed,ScienceDirect,and Web of Science,with the keywords of"gut microbiota","gut-brain axis",and "neuroscience".Study Selection:All relevant articles on gut microbiota and gut-brain axis were included and carefully reviewed,with no limitation of study design.Results:It is well-recognized that gut microbiota affects the brain's physiological,behavioral,and cognitive functions although its precise mechanism has not yet been fully understood.Gut microbiota-brain axis may include gut microbiota and their metabolic products,enteric nervous system,sympathetic and parasympathetic branches within the autonomic nervous system,neural-immune system,neuroendocrine system,and central nervous system.Moreover,there may be five communication routes between gut microbiota and brain,including the gut-brain's neural network,neuroendocrine-hypothalamic-pituitary-adrenal axis,gut immune system,some neurotransmitters and neural regulators synthesized by gut bacteria,and barrier paths including intestinal mucosal barrier and blood-brain barrier.The microbiome is used to define the composition and functional characteristics of gut microbiota,and metagenomics is an appropriate technique to characterize gut microbiota.Conclusions:Gut microbiota-brain axis refers to a bidirectional information network between the gut microbiota and the brain,which may provide a new way to protect the brain in the near future.

Food and the circadian activity of the hypothalamic-pituitary-adrenal axis

Directory of Open Access Journals (Sweden)

A.M.O. Leal

1997-12-01

Full Text Available Temporal organization is an important feature of biological systems and its main function is to facilitate adaptation of the organism to the environment. The daily variation of biological variables arises from an internal time-keeping system. The major action of the environment is to synchronize the internal clock to a period of exactly 24 h. The light-dark cycle, food ingestion, barometric pressure, acoustic stimuli, scents and social cues have been mentioned as synchronizers or" zeitgebers". The circadian rhythmicity of plasma corticosteroids has been well characterized in man and in rats and evidence has been accumulated showing daily rhythmicity at every level of the hypothalamic-pituitary-adrenal (HPA axis. Studies of restricted feeding in rats are of considerable importance because they reveal feeding as a major synchronizer of rhythms in HPA axis activity. The daily variation of the HPA axis stress response appears to be closely related to food intake as well as to basal activity. In humans, the association of feeding and HPA axis activity has been studied under physiological and pathological conditions such as anorexia nervosa, bulimia, malnutrition, obesity, diabetes mellitus and Cushing's syndrome. Complex neuroanatomical pathways and neurochemical circuitry are involved in feeding-associated HPA axis modulation. In the present review we focus on the interaction among HPA axis rhythmicity, food ingestion, and different nutritional and endocrine states

Biological and psychological markers of stress in humans: focus on the Trier Social Stress Test.

Science.gov (United States)

Allen, Andrew P; Kennedy, Paul J; Cryan, John F; Dinan, Timothy G; Clarke, Gerard

2014-01-01

Validated biological and psychological markers of acute stress in humans are an important tool in translational research. The Trier Social Stress Test (TSST), involving public interview and mental arithmetic performance, is among the most popular methods of inducing acute stress in experimental settings, and reliably increases hypothalamic-pituitary-adrenal axis activation. However, although much research has focused on HPA axis activity, the TSST also affects the sympathetic-adrenal-medullary system, the immune system, cardiovascular outputs, gastric function and cognition. We critically assess the utility of different biological and psychological markers, with guidance for future research, and discuss factors which can moderate TSST effects. We outline the effects of the TSST in stress-related disorders, and if these responses can be abrogated by pharmacological and psychological treatments. Modified TSST protocols are discussed, and the TSST is compared to alternative methods of inducing acute stress. Our analysis suggests that multiple readouts are necessary to derive maximum information; this strategy will enhance our understanding of the psychobiology of stress and provide the means to assess novel therapeutic agents. Copyright © 2013 Elsevier Ltd. All rights reserved.

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

Science.gov (United States)

Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

2016-06-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of Local Vibration and Passive Exercise on the Hormones and Neurotransmitters of Hypothalamic-Pituitary-Adrenal Axis in Hindlimb Unloading Rats

Science.gov (United States)

Luan, Huiqin; Huang, Yunfei; Li, Jian; Sun, Lianwen; Fan, Yubo

2018-04-01

Astronauts are severely affected by spaceflight-induced bone loss. Mechanical stimulation through exercise inhibits bone resorption and improves bone formation. Exercise and vibration can prevent the degeneration of the musculoskeletal system in tail-suspended rats, and long-term exercise stress will affect endocrine and immune systems that are prone to fatigue. However, the mechanisms through which exercise and vibration affect the endocrine system remain unknown. This study mainly aimed to investigate the changes in the contents of endocrine axis-related hormones and the effects of local vibration and passive exercise on hypothalamic-pituitary-adrenal (HPA) axis-related hormones in tail-suspended rats. A total of 32 Sprague-Dawley rats were randomly distributed into four groups (n = 8 per group): tail suspension (TS), TS + 35Hz vibration, TS + passive exercise, and control. The rats were placed on a passive exercise and local vibration regimen for 21 days. On day 22 of the experiment, the contents of corticotrophin-releasing hormone, adrenocorticotropic hormone, cortisol, and 5-hydroxytryptamine in the rats were quantified with kits in accordance with the manufacturer's instructions. Histomorphometry was applied to evaluate histological changes in the hypothalamus. Results showed that 35Hz local vibration cannot cause rats to remain in a stressed state and that it might not inhibit the function of the HPA axis. Therefore, we speculate that this local vibration intensity can protect the function of the HPA axis and helps tail-suspended rats to transition from stressed to adaptive state.

Expression and Function of Xmsx-2B in Dorso-Ventral Axis Formation in Gastrula Embryos.

Science.gov (United States)

Onitsuka, I; Takeda, M; Maéno, M

2000-11-01

Msx is a homeodomain-containing transcriptional factor that plays an essential role in pattern formation in vertebrata and invertebrata embryos. In Xenopus laevis, two msx genes have been identified (Xmsx-1 and Xmsx-2). In the present study, we attempted to elucidate the expression and function of Xmsx-2B (formerly designated as Xhox7.1') in early embryogenesis. Whole mount in situ hybridization analyses showed that the expression pattern of Xmsx-2B at gastrula and neurula stages was very similar to that of Xmsx-1: the transcript of Xmsx-2B was observed in ventral and lateral sides of the embryo. At the tailbud stage, however, the expression pattern of Xmsx-2B in neural tissues was distinct from that of Xmsx-1. An RNA injection experiment revealed that, like BMP-4, Xmsx-2B has a strong ventralizing activity. In the Xmsx-2B -injected embryos, differentiation of axial structures such as the notochord, muscle, and neural tissue was completely suppressed, whereas alpha-globin mRNA, a blood cell marker, was highly expressed. Simultaneous injection of Xmsx-1 and Xmsx-2B RNAs showed that they function in an additive manner. It was also shown that coinjection of Xmsx-2B with a dominant-negative BMP-4 receptor (tBR), which can induce formation of secondary axis when injected alone in ventral blastomeres, suppressed secondary axis formation. Furthermore, Xmsx-2B also suppressed secondary axis formation, which was induced by a dominant-negative form of Xmsx-1 (VP16/msx-1). Therefore, like Xmsx-1, Xmsx-2B is a downstream nuclear factor of the BMP-4-derived ventralizing signal, and these two factors probably share the same target molecules. In conclusion, Xmsx-1 and Xmsx-2B function in dorso-ventral axis formation in early Xenopus laevis development.

Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System.

Science.gov (United States)

Burford, Natalie G; Webster, Natalia A; Cruz-Topete, Diana

2017-10-16

The collective of endocrine organs acting in homeostatic regulation-known as the hypothalamic-pituitary-adrenal (HPA) axis-comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

Stress, memory, and the hippocampus.

Science.gov (United States)

Wingenfeld, Katja; Wolf, Oliver T

2014-01-01

Stress hormones, i.e. cortisol in human and cortisone in rodents, influence a wide range of cognitive functions, including hippocampus-based declarative memory performance. Cortisol enhances memory consolidation, but impairs memory retrieval. In this context glucocorticoid receptor sensitivity and hippocampal integrity play an important role. This review integrates findings on the relationships between the hypothalamus-pituitary-adrenal (HPA) axis, one of the main coordinators of the stress response, hippocampus, and memory. Findings obtained in healthy participants will be compared with selected mental disorders, including major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and borderline personality disorder (BPD). These disorders are characterized by alterations of the HPA axis and hippocampal dysfunctions. Interestingly, the acute effects of stress hormones on memory in psychiatric patients are different from those found in healthy humans. While cortisol administration has failed to affect memory retrieval in patients with MDD, patients with PTSD and BPD have been found to show enhanced rather than impaired memory retrieval after hydrocortisone. This indicates an altered sensitivity to stress hormones in these mental disorders. © 2014 S. Karger AG, Basel

Interoception and Stress

Directory of Open Access Journals (Sweden)

André eSchulz

2015-07-01

Full Text Available Afferent neural signals are continuously transmitted from visceral organs to the brain. Interoception refers to the processing of visceral-afferent neural signals by the central nervous system, which can finally result in the conscious perception of bodily processes. Interoception can, therefore, be described as a prominent example of information processing on the ascending branch of the brain-body axis. Stress responses involve a complex neuro-behavioral cascade, which is elicited when the organism is confronted with a potentially harmful stimulus. As this stress cascade comprises a range of neural and endocrine pathways, stress can be conceptualized as a communication process on the descending branch of the brain-body axis. Interoception and stress are, therefore, associated via the bi-directional transmission of information on the brain-body axis. It could be argued that excessive and/or enduring activation (e.g. by acute or chronic stress of neural circuits, which are responsible for successful communication on the brain-body axis, induces malfunction and dysregulation of these information processes. As a consequence, interoceptive signal processing may be altered, resulting in physical symptoms contributing to the development and/or maintenance of body-related mental disorders, which are associated with stress. In the current paper, we summarize findings on psychobiological processes underlying acute and chronic stress and their interaction with interoception. While focusing on the role of the physiological stress axes (HPA axis and autonomic nervous system, psychological factors in acute and chronic stress are also discussed. We propose a feed-forward model involving stress (in particular early life or chronic stress, as well as major adverse events, the dysregulation of physiological stress axes, altered perception of bodily sensations, and the generation of physical symptoms, which may in turn facilitate stress.

Energetic stress: The reciprocal relationship between energy availability and the stress response.

Science.gov (United States)

Harrell, C S; Gillespie, C F; Neigh, G N

2016-11-01

The worldwide epidemic of metabolic syndromes and the recognized burden of mental health disorders have driven increased research into the relationship between the two. A maladaptive stress response is implicated in both mental health disorders and metabolic disorders, implicating the hypothalamic-pituitary-adrenal (HPA) axis as a key mediator of this relationship. This review explores how an altered energetic state, such as hyper- or hypoglycemia, as may be manifested in obesity or diabetes, affects the stress response and the HPA axis in particular. We propose that changes in energetic state or energetic demands can result in "energetic stress" that can, if prolonged, lead to a dysfunctional stress response. In this review, we summarize the role of the hypothalamus in modulating energy homeostasis and then briefly discuss the relationship between metabolism and stress-induced activation of the HPA axis. Next, we examine seven mechanisms whereby energetic stress interacts with neuroendocrine stress response systems, including by glucocorticoid signaling both within and beyond the HPA axis; by nutrient-induced changes in glucocorticoid signaling; by impacting the sympathetic nervous system; through changes in other neuroendocrine factors; by inducing inflammatory changes; and by altering the gut-brain axis. Recognizing these effects of energetic stress can drive novel therapies and prevention strategies for mental health disorders, including dietary intervention, probiotics, and even fecal transplant. Copyright © 2015 Elsevier Inc. All rights reserved.

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

Science.gov (United States)

Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

2016-01-01

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that

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

Science.gov (United States)

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

Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

Science.gov (United States)

Jiang, Sunny Zhihong; Eiden, Lee E

2016-07-01

We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

Development of the adrenal axis in the neonatal rat

Energy Technology Data Exchange (ETDEWEB)

Guillet, Ronnie [Univ. of Rochester, NY (United States)

1977-01-01

Plasma corticosterone and ACTH concentrations were determined in neonatal rats 1, 7, 14, and 21 days old, under a variety of experimental conditions, to obtain more information on the postnatal development of the rat hypothalamo-adrenal (HHA) axis. The results indicate that: (1) there is a diminution followed by an increase in responsiveness of the adrenal gland, but the pituitary response to direct hormonal stimulation is unchanged during the first three postnatal weeks; (2) continued stimulation of the adrenal by ACTH or of the central nervous system (CNS) or hypothalamus by corticosterone is necessary during early postnatal development to allow normal maturation of the HHA axis; and (3) feedback inhibition is operative by birth, at least to a moderate degree. Taken together, the studies suggest that both the adrenal and pituitary glands are potentially functional at birth, but that the hypothalamic and CNS mediators of the stress response are not mature until at least the second or third postnatal week. (ERB)

Salivary cortisol and dehydroepiandrosterone sulfate in adolescent rape victims with post traumatic stress disorder

NARCIS (Netherlands)

Bicanic, Iva A. E.; Postma, Riemke M.; Sinnema, Gerben; de Roos, Carlijn; Olff, Miranda; van Wesel, Floryt; van de Putte, Elise M.

2013-01-01

In chronic sexual abuse victims with post traumatic stress disorder (PTSD), the hypothalamic pituitary adrenal (HPA) axis can be dysregulated. In single rape victims, PTSD symptoms are hypothesized to function as a chronic stressor leading to similar HPA-axis dysregulation. The objective of the

C-axis orientated AlN films deposited using deep oscillation magnetron sputtering

International Nuclear Information System (INIS)

Lin, Jianliang; Chistyakov, Roman

2017-01-01

Highlights: • Highly orientated AlN films were deposited by DOMS technique. • Controlled ion flux bombardment improved the texture and crystalline quality. • Excessive ion bombardment showed a detrimental effect on the c-axis orientation growth. • Improved c-axis alignment accompanied with stress relaxation with increasing film thickness. - Abstract: Highly c-axis orientated aluminum nitride (AlN) films were deposited on silicon (100) substrates by reactive deep oscillation magnetron sputtering (DOMS). No epitaxial favored bond layer and substrate heating were applied for assisting texture growth. The effects of the peak target current density (varied from 0.39 to 0.8 Acm"−"2) and film thickness (varied from 0.25 to 3.3 μm) on the c-axis orientation, microstructure, residual stress and mechanical properties of the AlN films were investigated by means of X-ray diffraction rocking curve methodology, transmission electron microscopy, optical profilometry, and nanoindentation. All AlN films exhibited a preferred orientation and compressive residual stresses. At similar film thicknesses, an increase in the peak target current density to 0.53 Acm"−"2 improved the orientation. Further increasing the peak target current density to above 0.53 Acm"−"2 showed limited contribution to the texture development. The study also showed that an increase in the thickness of the AlN films deposited by DOMS improved the c-axis alignment accompanied with a reduction in the residual stress.

C-axis orientated AlN films deposited using deep oscillation magnetron sputtering

Energy Technology Data Exchange (ETDEWEB)

Lin, Jianliang, E-mail: Jianliang.lin@swri.org [Southwest Research Institute, San Antonio, TX 78238 (United States); Chistyakov, Roman [Zpulser LLC, Mansfield, MA 02048 (United States)

2017-02-28

Highlights: • Highly <0001> orientated AlN films were deposited by DOMS technique. • Controlled ion flux bombardment improved the <0001> texture and crystalline quality. • Excessive ion bombardment showed a detrimental effect on the c-axis orientation growth. • Improved c-axis alignment accompanied with stress relaxation with increasing film thickness. - Abstract: Highly <0001> c-axis orientated aluminum nitride (AlN) films were deposited on silicon (100) substrates by reactive deep oscillation magnetron sputtering (DOMS). No epitaxial favored bond layer and substrate heating were applied for assisting texture growth. The effects of the peak target current density (varied from 0.39 to 0.8 Acm{sup −2}) and film thickness (varied from 0.25 to 3.3 μm) on the c-axis orientation, microstructure, residual stress and mechanical properties of the AlN films were investigated by means of X-ray diffraction rocking curve methodology, transmission electron microscopy, optical profilometry, and nanoindentation. All AlN films exhibited a <0001> preferred orientation and compressive residual stresses. At similar film thicknesses, an increase in the peak target current density to 0.53 Acm{sup −2} improved the <0001> orientation. Further increasing the peak target current density to above 0.53 Acm{sup −2} showed limited contribution to the texture development. The study also showed that an increase in the thickness of the AlN films deposited by DOMS improved the c-axis alignment accompanied with a reduction in the residual stress.

Use of cognitive behavior therapy for functional hypothalamic amenorrhea.

Science.gov (United States)

Berga, Sarah L; Loucks, Tammy L

2006-12-01

Behaviors that chronically activate the hypothalamic-pituitary-adrenal (HPA) axis and/or suppress the hypothalamic-pituitary-thyroidal (HPT) axis disrupt the hypothalamic-pituitary-gonadal axis in women and men. Individuals with functional hypothalamic hypogonadism typically engage in a combination of behaviors that concomitantly heighten psychogenic stress and increase energy demand. Although it is not widely recognized clinically, functional forms of hypothalamic hypogonadism are more than an isolated disruption of gonadotropin-releasing hormone (GnRH) drive and reproductive compromise. Indeed, women with functional hypothalamic amenorrhea display a constellation of neuroendocrine aberrations that reflect allostatic adjustments to chronic stress. Given these considerations, we have suggested that complete neuroendocrine recovery would involve more than reproductive recovery. Hormone replacement strategies have limited benefit because they do not ameliorate allostatic endocrine adjustments, particularly the activation of the adrenal and the suppression of the thyroidal axes. Indeed, the rationale for the use of sex steroid replacement is based on the erroneous assumption that functional forms of hypothalamic hypogonadism represent only or primarily an alteration in the hypothalamic-pituitary-gonadal axis. Potential health consequences of functional hypothalamic amenorrhea, often termed stress-induced anovulation, may include an increased risk of cardiovascular disease, osteoporosis, depression, other psychiatric conditions, and dementia. Although fertility can be restored with exogenous administration of gonadotropins or pulsatile GnRH, fertility management alone will not permit recovery of the adrenal and thyroidal axes. Initiating pregnancy with exogenous means without reversing the hormonal milieu induced by chronic stress may increase the likelihood of poor obstetrical, fetal, or neonatal outcomes. In contrast, behavioral and psychological interventions that

Metabotropic glutamate receptor subtype 7 ablation causes dysregulation of the HPA axis and increases hippocampal BDNF protein levels: implications for stress-related psychiatric disorders.

Science.gov (United States)

Mitsukawa, Kayo; Mombereau, Cedric; Lötscher, Erika; Uzunov, Doncho P; van der Putten, Herman; Flor, Peter J; Cryan, John F

2006-06-01

Regulation of neurotransmission via group-III metabotropic glutamate receptors (mGluR4, -6, -7, and -8) has recently been implicated in the pathophysiology of affective disorders, such as major depression and anxiety. For instance, mice with a targeted deletion of the gene for mGluR7 (mGluR7-/-) showed antidepressant and anxiolytic-like effects in a variety of stress-related paradigms, including the forced swim stress and the stress-induced hyperthermia tests. Deletion of mGluR7 reduces also amygdala- and hippocampus-dependent conditioned fear and aversion responses. Since the hypothalamic-pituitary-adrenal (HPA) axis regulates the stress response we investigate whether parameters of the HPA axis at the levels of selected mRNA transcripts and endocrine hormones are altered in mGluR7-deficient mice. Over all, mGluR7-/- mice showed only moderately lower serum levels of corticosterone and ACTH compared with mGluR7+/+ mice. More strikingly however, we found strong evidence for upregulated glucocorticoid receptor (GR)-dependent feedback suppression of the HPA axis in mice with mGluR7 deficiency: (i) mRNA transcripts of GR were significantly upregulated in the hippocampus of mGluR7-/- animals, (ii) similar increases were seen with 5-HT1A receptor transcripts, which are thought to be directly controlled by the transcription factor GR and finally (iii) mGluR7-/- mice showed elevated sensitivity to dexamethasone-induced suppression of serum corticosterone when compared with mGluR7+/+ animals. These results indicate that mGluR7 deficiency causes dysregulation of HPA axis parameters, which may account, at least in part, for the phenotype of mGluR7-/- mice in animal models for anxiety and depression. In addition, we present evidence that protein levels of brain-derived neurotrophic factor are also elevated in the hippocampus of mGluR7-/- mice, which we discuss in the context of the antidepressant-like phenotype found in those animals. We conclude that genetic ablation of m

Evidence against a critical role of CB1 receptors in adaptation of the hypothalamic-pituitary-adrenal axis and other consequences of daily repeated stress.

Science.gov (United States)

Rabasa, Cristina; Pastor-Ciurana, Jordi; Delgado-Morales, Raúl; Gómez-Román, Almudena; Carrasco, Javier; Gagliano, Humberto; García-Gutiérrez, María S; Manzanares, Jorge; Armario, Antonio

2015-08-01

There is evidence that endogenous cannabinoids (eCBs) play a role in the control of the hypothalamic-pituitary-adrenal (HPA) axis, although they appear to have dual, stimulatory and inhibitory, effects. Recent data in rats suggest that eCBs, acting through CB1 receptors (CB1R), may be involved in adaptation of the HPA axis to daily repeated stress. In the present study we analyze this issue in male mice and rats. Using a knock-out mice for the CB1 receptor (CB1-/-) we showed that mutant mice presented similar adrenocorticotropic hormone (ACTH) response to the first IMO as wild-type mice. Daily repeated exposure to 1h of immobilization reduced the ACTH response to the stressor, regardless of the genotype, demonstrating that adaptation occurred to the same extent in absence of CB1R. Prototypical changes observed after repeated stress such as enhanced corticotropin releasing factor (CRH) gene expression in the paraventricular nucleus of the hypothalamus, impaired body weight gain and reduced thymus weight were similarly observed in both genotypes. The lack of effect of CB1R in the expression of HPA adaptation to another similar stressor (restraint) was confirmed in wild-type CD1 mice by the lack of effect of the CB1R antagonist AM251 just before the last exposure to stress. Finally, the latter drug did not blunt the HPA, glucose and behavioral adaptation to daily repeated forced swim in rats. Thus, the present results indicate that CB1R is not critical for overall effects of daily repeated stress or proper adaptation of the HPA axis in mice and rats. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

The role of BDNF and HPA axis in the neurobiology of burnout syndrome.

Science.gov (United States)

Onen Sertoz, Ozen; Tolga Binbay, Ibrahim; Koylu, Ersin; Noyan, Aysin; Yildirim, Emre; Elbi Mete, Hayriye

2008-08-01

Chronic stress is known to affect the HPA axis. The few clinical studies which have been conducted on HPA-axis function in burnout have produced inconsistent results. The etiological relationship between sBDNF and burnout has not yet been studied. The aim of the current study was to investigate the role of BDNF and HPA axis in the neurobiology of burnout. In the current study 37 clinically diagnosed burnout participants were compared with 35 healthy controls in terms of BDNF, HPA axis, burnout symptoms, depression, anxiety and psychosomatic complaints. Basal serum cortisol, sBDNF and cortisol level after 1 mg DST was sampled. We found no significant differences in terms of HPA-axis function (for basal serum cortisol, p=0.592; for cortisol level after 1 mg DST, p=0.921), but we did find lowered sBDNF levels in burnout group (88.66+/-18.15 pg/ml) as compared to healthy controls (102.18+/-20.92 pg/ml) and the difference was statistically significant (p=0.005). Logistic Regression Analysis revealed that emotional exhaustion (p=0.05), depersonalization (p=0.005) and depression (p=0.025) were significantly associated with burnout. sBDNF levels correlated negatively with emotional exhaustion (r=-,268, p=0.026), depersonalization (r=-,333, p=0.005) and correlated positively with competence (r=0.293, p=0.015) sub-scales of burnout inventory. However, there were no significant relationships between cortisol levels and sBDNF levels (r=0.80, p=0.51), depression, anxiety, psychosomatic complaints and burnout inventory. Our results suggest that low BDNF might contribute to the neurobiology of burnout syndrome and it seems to be associated with burnout symptoms including altered mood and cognitive functions.

Frequent cellular phone use modifies hypothalamic-pituitary-adrenal axis response to a cellular phone call after mental stress in healthy children and adolescents: A pilot study.

Science.gov (United States)

Geronikolou, Styliani A; Chamakou, Aikaterini; Mantzou, Aimilia; Chrousos, George; KanakaGantenbein, Christina

2015-12-01

The hypothalamic-pituitary-adrenal (HPA) axis is the main "gate-keeper" of the organism's response to every somatic or mental stress. This prospective study aims to investigate the HPA-axis response to a cellular phone call exposure after mental stress in healthy children and adolescents and to assess the possible predictive role of baseline endocrine markers to this response. Two groups of healthy school-age children aged 11-14 (12.5±1.5) years were included in the study, the one comprising those who are occasional users of a cellular phone (Group A) while the second those who do regularly use one (Group B). Blood samples were obtained from all participants at 8.00 am after a 12-hour overnight fasting for thyroid hormone, glucose, insulin, and cortisol levels determination. The participants performed the Trier Social Stress Test for Children (TSST-C) (5 minoral task followed by 5 min arithmetic task). Salivary cortisol samples were obtained at baseline, 10' and 20' min after the TSST-C and 10' and 20' after a 5 minute cellular phone call. Significant changes in the salivary cortisol levels were noted between 10' and 20' mins after the cellular phone call with different responses between the two groups. Baseline thyroid hormone levels seem to predict the cortisol response to mental stress mainly in group A, while HOMA had no impact on salivary cortisol response at any phase of the test, in either group. HPA axis response to cellular phone after mental stress in children and adolescents follow a different pattern in frequent users than in occasional users that seems to be influenced by the baseline thyroid hormone levels. Copyright © 2015 Elsevier B.V. All rights reserved.

Hypothalamic–pituitary–adrenal and hypothalamic–pituitary–gonadal axes: sex differences in regulation of stress responsivity

Science.gov (United States)

Oyola, Mario G.; Handa, Robert J.

2018-01-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic–pituitary–adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism’s response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic–pituitary–gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life. PMID:28859530

Hypothalamic-pituitary-adrenal and hypothalamic-pituitary-gonadal axes: sex differences in regulation of stress responsivity.

Science.gov (United States)

Oyola, Mario G; Handa, Robert J

2017-09-01

Gonadal hormones play a key role in the establishment, activation, and regulation of the hypothalamic-pituitary-adrenal (HPA) axis. By influencing the response and sensitivity to releasing factors, neurotransmitters, and hormones, gonadal steroids help orchestrate the gain of the HPA axis to fine-tune the levels of stress hormones in the general circulation. From early life to adulthood, gonadal steroids can differentially affect the HPA axis, resulting in sex differences in the responsivity of this axis. The HPA axis influences many physiological functions making an organism's response to changes in the environment appropriate for its reproductive status. Although the acute HPA response to stressors is a beneficial response, constant activation of this circuitry by chronic or traumatic stressful episodes may lead to a dysregulation of the HPA axis and cause pathology. Compared to males, female mice and rats show a more robust HPA axis response, as a result of circulating estradiol levels which elevate stress hormone levels during non-threatening situations, and during and after stressors. Fluctuating levels of gonadal steroids in females across the estrous cycle are a major factor contributing to sex differences in the robustness of HPA activity in females compared to males. Moreover, gonadal steroids may also contribute to epigenetic and organizational influences on the HPA axis even before puberty. Correspondingly, crosstalk between the hypothalamic-pituitary-gonadal (HPG) and HPA axes could lead to abnormalities of stress responses. In humans, a dysregulated stress response is one of the most common symptoms seen across many neuropsychiatric disorders, and as a result, such interactions may exacerbate peripheral pathologies. In this review, we discuss the HPA and HPG axes and review how gonadal steroids interact with the HPA axis to regulate the stress circuitry during all stages in life.

Dynamic transitions in a model of the hypothalamic-pituitary-adrenal axis

Science.gov (United States)

Čupić, Željko; Marković, Vladimir M.; Maćešić, Stevan; Stanojević, Ana; Damjanović, Svetozar; Vukojević, Vladana; Kolar-Anić, Ljiljana

2016-03-01

Dynamic properties of a nonlinear five-dimensional stoichiometric model of the hypothalamic-pituitary-adrenal (HPA) axis were systematically investigated. Conditions under which qualitative transitions between dynamic states occur are determined by independently varying the rate constants of all reactions that constitute the model. Bifurcation types were further characterized using continuation algorithms and scale factor methods. Regions of bistability and transitions through supercritical Andronov-Hopf and saddle loop bifurcations were identified. Dynamic state analysis predicts that the HPA axis operates under basal (healthy) physiological conditions close to an Andronov-Hopf bifurcation. Dynamic properties of the stress-control axis have not been characterized experimentally, but modelling suggests that the proximity to a supercritical Andronov-Hopf bifurcation can give the HPA axis both, flexibility to respond to external stimuli and adjust to new conditions and stability, i.e., the capacity to return to the original dynamic state afterwards, which is essential for maintaining homeostasis. The analysis presented here reflects the properties of a low-dimensional model that succinctly describes neurochemical transformations underlying the HPA axis. However, the model accounts correctly for a number of experimentally observed properties of the stress-response axis. We therefore regard that the presented analysis is meaningful, showing how in silico investigations can be used to guide the experimentalists in understanding how the HPA axis activity changes under chronic disease and/or specific pharmacological manipulations.

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats

Energy Technology Data Exchange (ETDEWEB)

Sena, Gabriela C.; Freitas-Lima, Leandro C.; Merlo, Eduardo; Podratz, Priscila L.; Araújo, Julia F.P. de [Department of Morphology, Federal University of Espírito Santo (Brazil); Brandão, Poliane A.A.; Carneiro, Maria T.W.D. [Department of Chemistry, Federal University of Espírito Santo (Brazil); Zicker, Marina C. [Department of Food Science, Faculty of Pharmacy, Federal University of Minas Gerais (Brazil); Ferreira, Adaliene V.M. [Department of Basic Nursing, Nursing School, Federal University of Minas Gerais (Brazil); Takiya, Christina M.; Lemos Barbosa, Carolina M. de; Morales, Marcelo M. [Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (Brazil); Santos-Silva, Ana Paula [Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro (Brazil); Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (Brazil); Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro (Brazil); Miranda-Alves, Leandro [Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro (Brazil); Postgraduate Program in Endocrinology, School of Medicine, Federal University of Rio de Janeiro (Brazil); Silva, Ian V. [Department of Morphology, Federal University of Espírito Santo (Brazil); Graceli, Jones B., E-mail: jbgraceli@gmail.com [Department of Morphology, Federal University of Espírito Santo (Brazil)

2017-03-15

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats

International Nuclear Information System (INIS)

Sena, Gabriela C.; Freitas-Lima, Leandro C.; Merlo, Eduardo; Podratz, Priscila L.; Araújo, Julia F.P. de; Brandão, Poliane A.A.; Carneiro, Maria T.W.D.; Zicker, Marina C.; Ferreira, Adaliene V.M.; Takiya, Christina M.; Lemos Barbosa, Carolina M. de; Morales, Marcelo M.; Santos-Silva, Ana Paula; Miranda-Alves, Leandro; Silva, Ian V.; Graceli, Jones B.

2017-01-01

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100 ng/kg/day) for 15 days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may

Elastic-plastic analysis of an axi-symmetric problem by a finite element method

International Nuclear Information System (INIS)

Isozaki, Toshikuni

1984-06-01

Generally speaking, many structures are designed and fabricated on the basis of an axi-symmetric structure. Finite Element Method is the capable method to solve these axi-symmetric problems beyond the elastic limit. As the first step to solve these problems, the computer program for the elastic-plastic analysis of the axi-symmetric problem is composed. The basic program is based upon that described in Zienkiewicz's text book to solve the elastic plane stress problem, taking the plastic stress matrix by Yamada's method into consideration and it is converted to solve the axi-symmetric problem. For the verification of the program, the plane strain problem of a cylindrical tube under internal pressure was solved. The computed results were compared with those shown in ADINA's user's manual. They showed close agreement. (author)

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

Science.gov (United States)

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

2016-01-01

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

Measurement of residual stresses using fracture mechanics weight functions

International Nuclear Information System (INIS)

Fan, Y.

2000-01-01

A residual stress measurement method has been developed to quantify through-the-thickness residual stresses. Accurate measurement of residual stresses is crucial for many engineering structures. Fabrication processes such as welding and machining generate residual stresses that are difficult to predict. Residual stresses affect the integrity of structures through promoting failures due to brittle fracture, fatigue, stress corrosion cracking, and wear. In this work, the weight function theory of fracture mechanics is used to measure residual stresses. The weight function theory is an important development in computational fracture mechanics. Stress intensity factors for arbitrary stress distribution on the crack faces can be accurately and efficiently computed for predicting crack growth. This paper demonstrates that the weight functions are equally useful in measuring residual stresses. In this method, an artificial crack is created by a thin cut in a structure containing residual stresses. The cut relieves the residual stresses normal to the crack-face and allows the relieved residual stresses to deform the structure. Strain gages placed adjacent to the cut measure the relieved strains corresponding to incrementally increasing depths of the cut. The weight functions of the cracked body relate the measured strains to the residual stresses normal to the cut within the structure. The procedure details, such as numerical integration of the singular functions in applying the weight function method, will be discussed

Measurement of residual stresses using fracture mechanics weight functions

International Nuclear Information System (INIS)

Fan, Y.

2001-01-01

A residual stress measurement method has been developed to quantify through-the-thickness residual stresses. Accurate measurement of residual stresses is crucial for many engineering structures. Fabrication processes such as welding and machining generate residual stresses that are difficult to predict. Residual stresses affect the integrity of structures through promoting failures due to brittle fracture, fatigue, stress corrosion cracking, and wear. In this work, the weight function theory of fracture mechanics is used to measure residual stresses. The weight function theory is an important development in computational fracture mechanics. Stress intensity factors for arbitrary stress distribution on the crack faces can be accurately and efficiently computed for predicting crack growth. This paper demonstrates that the weight functions are equally useful in measuring residual stresses. In this method, an artificial crack is created by a thin cut in a structure containing residual stresses. The cut relieves the residual stresses normal to the crack-face and allows the relieved residual stresses to deform the structure. Strain gages placed adjacent to the cut measure the relieved strains corresponding to incrementally increasing depths of the cut. The weight functions of the cracked body relate the measured strains to the residual stresses normal to the cut within the structure. The procedure details, such as numerical integration of the singular functions in applying the weight function method, will be discussed. (author)

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

NARCIS (Netherlands)

Dieleman, G.C.; Huizink, A.C.; Tulen, J.H.M.; Utens, E.M.W.J.; Creemers, H.E.; van der Ende, J.; Verhulst, F.C.

2015-01-01

Background: It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different

Alterations in HPA-axis and autonomic nervous system functioning in childhood anxiety disorders point to a chronic stress hypothesis

NARCIS (Netherlands)

Dieleman, Gwendolyn C.; Huizink, Anja C.; Tulen, Joke H. M.; Utens, Elisabeth M. W. J.; Creemers, Hanneke E.; van der Ende, Jan; Verhulst, Frank C.

2015-01-01

It is of debate whether or not childhood anxiety disorders (AD) can be captured by one taxonomic construct. This study examined whether perceived arousal (PA), autonomic nervous system (ANS) and hypothalamic-pituitary-adrenal (HPA) axis measures can distinguish children with different primary

Effects of in-plane compressive stress on electrical properties of (Ba,Sr)TiO3 thin film capacitors prepared by on- and off-axis rf magnetron sputtering

International Nuclear Information System (INIS)

Park, Woo Young; Ahn, Kun Ho; Hwang, Cheol Seong

2003-01-01

This study investigated the structural and electrical properties of (Ba,Sr)TiO 3 (BST) thin film capacitors with thicknesses ranging from 18 to 215 nm, which were prepared by on- and off-axis rf magnetron sputtering technique on Pt/SiO 2 /Si substrates. The deposition rate and cation composition ratios of the films were controlled to be the same regardless of the sputtering geometry. All the films show elongations in the out-of-plane lattice spacing, suggesting the presence of compressive stress with a smaller value by on-axis sputtering than by the off-axis system. There was no thickness dependence of the strain in the polycrystalline BST films. The BST films deposited using the on-axis system showed a higher bulk dielectric constant with a higher interfacial capacitance and a lower leakage current level than the films produced by the off-axis system. The strain effect was proposed to explain the correlations between the structural and electrical properties

Racism-Related Stress, General Life Stress, and Psychological Functioning among Black American Women

Science.gov (United States)

Pieterse, Alex L.; Carter, Robert T.; Ray, Kilynda V.

2013-01-01

The relationship between general life stress, perceived racism, and psychological functioning was explored in a sample of 118 Black American women. Findings indicate that racism-related stress was not a significant predictor of psychological functioning when controlling for general life stress. Perceived racism was positively associated with…

Measurement of multiaxial ply strength by an off-axis flexure test

Science.gov (United States)

Crews, John H., Jr.; Naik, Rajiv A.

1992-01-01

An off-axis flexure (OAF) test was performed to measure ply strength under multiaxial stress states. This test involves unidirectional off-axis specimens loaded in bending, using an apparatus that allows these anisotropic specimens to twist as well as flex without the complications of a resisting torque. A 3D finite element stress analysis verified that simple beam theory could be used to compute the specimen bending stresses at failure. Unidirectional graphite/epoxy specimens with fiber angles ranging from 90 deg to 15 deg have combined normal and shear stresses on their failure planes that are typical of 45 deg plies in structural laminates. Tests for a range of stress states with AS4/3501-6 specimens showed that both normal and shear stresses on the failure plane influenced cracking resistance. This OAF test may prove to be useful for generating data needed to predict ply cracking in composite structures and may also provide an approach for studying fiber-matrix interface failures under stress states typical of structures.

Recovery of HPA Axis Function After Successful Gonadotropin-Induced Pregnancy and Delivery in a Woman With Panhypopituitarism: Case Report and Review.

Science.gov (United States)

Wang, Yi; Zhang, Qiongyue; Yang, Jianzhi; Zhao, Xiaolong; He, Min; Shou, Xuefei; Li, Shiqi; Li, Yiming; Wang, Yongfei; Ye, Hongying

2015-09-01

Hypopituitarism is defined as the partial or complete defect of anterior pituitary hormone secretion. Patients with hypopituitarism usually need life-long hormone replacement therapy. However, in this case, we report a patient with panhypopituitarism whose hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered after pregnancy and delivery. In this case study, we reported the case management and conducted a review of literature to identify the possible mechanism of pituitary function recovery. The patient who suffered from secondary amenorrhea was found a nonfunctioning pituitary macroadenoma, and the hormone test showed serum cortisol, FT3, FT4, thyrotropic hormone, and prolactin were at normal range. After surgical removal of the tumor which invasion in the sellar region, the patient had panhypopituitarism confirmed by the routine hormone test. Though spontaneous pregnancy is impossible in female patients with panhypopituitarism, the patient was restored fertility by the help of artificial reproductive techniques. After the confirmation of the pregnancy, levothyroixine was increased to 75 μg daily and readjusted to 150 μg daily before delivery according to the monthly measurement thyroid function. Hydrocortisone 10 mg daily replaced cortisone acetate; the dose was increased according to the symptoms of morning sickness. A single stress dose of hydrocortisone (200 mg) was used before elective cesarean delivery and was tapered to the dose of 10 mg per day in 1 week. Levothyroixine was reduced to 75 μg daily after delivery. During follow-up, her hypothalamus-pituitary-adrenal (HPA) axis function was completely recovered. The peak serum cortisol level could increase to 19.08 μg/dL by insulin-induced hypoglycemia. However, growth hormone remained unresponsive to the insulin-tolerance test, and thyroid hormone still needed exogenous supplementation. Hormone replacement therapy needed closely followed by endocrinologist and multidisciplinary

Taurine and pioglitazone attenuate diabetes-induced testicular damage by abrogation of oxidative stress and up-regulation of the pituitary-gonadal axis.

Science.gov (United States)

Abd El-Twab, Sanaa M; Mohamed, Hanaa M; Mahmoud, Ayman M

2016-06-01

Chronic hyperglycemia is associated with impairment of testicular function. The current study aimed to investigate the protective effects and the possible mechanisms of taurine and pioglitazone against diabetes-induced testicular dysfunction in rats. Diabetes was induced by streptozotocin injection. Both normal and diabetic rats received taurine (100 mg/kg) or pioglitazone (10 mg/kg) orally and daily for 6 weeks. Diabetic rats showed a significant (P Taurine and pioglitazone alleviated hyperglycemia, decreased pro-inflammatory cytokines, and increased circulating levels of insulin, testosterone, LH, and FSH. Gene and protein expression of LH and FSH receptors and cytochrome P450 17α-hydroxylase (CYP17) was significantly (P taurine and pioglitazone. In addition, taurine and pioglitazone significantly decreased lipid peroxidation and DNA damage, and enhanced activity of the antioxidant enzymes in testes of diabetic rats. In conclusion, taurine and pioglitazone exerted protective effects against diabetes-induced testicular damage through attenuation of hyperglycemia, inflammation, oxidative stress and DNA damage, and up-regulation of the pituitary/gonadal axis.

Effect of Heat Stress on the Expression of GABA Receptor mRNA in the HPG Axis of Wenchang Chickens

Directory of Open Access Journals (Sweden)

LJ Xie

Full Text Available ABSTRACT We investigated the effect of heat stress (HS on the expression of the GABA receptor in the hypothalamic-pituitary-gonadal (HPG axis of Wenchang chickens. Real-time quantitative RT-PCR (qRT-PCR was used to quantify the GABA receptor mRNA levels along the HPG axis of chickens under HS (40±0.5 °C for 1-6 weeks. Our results showed that the expression of GABAA and GABAB receptor at the mRNAs levels in the tissues of HPG axis exhibited fluctuation and variability. After HS, the mRNA level of GABAA receptor was significantly reduced in the hypothalamus of 1-week-old and in the pituitary of 3-week-old chickens, but significantly increased in the pituitary of 1-, 4-, and 5-week-old chickens. The GABAB receptor mRNA level significantly declined in the hypothalamus of 1-week-old and in the pituitary of 3-week-old chickens, but was significantly upregulated in the pituitary and testis of 1- and 2-week-old chickens. At other time points, the expressions of GABAA receptor and GABAB receptor showed no significant differences compared with control group. These results indicated that the levels of GABAA receptor and GABAB receptor mRNAs varied in different tissues of the HPG axis in chickens of different ages, displaying temporal and spatial variations. GABA receptor behaved as a positively-regulated gene by HS, i.e., its mRNA was increased by HS; similarly, it was a negatively-regulated gene by HS, when its expression was reduced by HS.

Stress and visceral pain: focusing on irritable bowel syndrome.

Science.gov (United States)

Fukudo, Shin

2013-12-01

Recent advances in brain science have shown that the brain function encoding emotion depends on interoceptive signals such as visceral pain. Visceral pain arose early in our evolutionary history. Bottom-up processing from gut-to-brain and top-down autonomic/neuroendocrine mechanisms in brain-to-gut signaling constitute a circuit. Brain imaging techniques have enabled us to depict the visceral pain pathway as well as the related emotional circuit. Irritable bowel syndrome (IBS) is characterized by chronic recurrent abdominal pain or abdominal discomfort associated with bowel dysfunction. It is also thought to be a disorder of the brain-gut link associated with an exaggerated response to stress. Corticotropin-releasing hormone (CRH), a major mediator of the stress response in the brain-gut axis, is an obvious candidate in the pathophysiology of IBS. Indeed, administration of CRH has been shown to aggravate the visceral sensorimotor response in IBS patients, and the administration of peptidergic CRH antagonists seems to alleviate IBS pathophysiology. Serotonin (5-HT) is another likely candidate associated with brain-gut function in IBS, as 5-HT3 antagonists, 5-HT4 agonists, and antidepressants were demonstrated to regulate 5-HT neurotransmission in IBS patients. Autonomic nervous system function, the neuroimmune axis, and the brain-gut-microbiota axis show specific profiles in IBS patients. Further studies on stress and visceral pain neuropathways in IBS patients are warranted. Copyright © 2013 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Hypothalamic-Pituitary-Adrenal Axis Modulation of Glucocorticoids in the Cardiovascular System

Directory of Open Access Journals (Sweden)

Natalie G. Burford

2017-10-01

Full Text Available The collective of endocrine organs acting in homeostatic regulation—known as the hypothalamic-pituitary-adrenal (HPA axis—comprises an integration of the central nervous system as well as peripheral tissues. These organs respond to imminent or perceived threats that elicit a stress response, primarily culminating in the release of glucocorticoids into the systemic circulation by the adrenal glands. Although the secretion of glucocorticoids serves to protect and maintain homeostasis in the typical operation at baseline levels, inadequate regulation can lead to physiologic and psychologic pathologies. The cardiovascular system is especially susceptible to prolonged dysregulation of the HPA axis and glucocorticoid production. There is debate about whether cardiovascular health risks arise from the direct detrimental effects of stress axis activation or whether pathologies develop secondary to the accompanying metabolic strain of excess glucocorticoids. In this review, we will explore the emerging research that indicates stress does have direct effects on the cardiovascular system via the HPA axis activation, with emphasis on the latest research on the impact of glucocorticoids signaling in the vasculature and the heart.

Cushing's Syndrome and Hypothalamic-Pituitary-Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy.

Science.gov (United States)

van Haalen, Femke M; van Dijk, Elon H C; Dekkers, Olaf M; Bizino, Maurice B; Dijkman, Greet; Biermasz, Nienke R; Boon, Camiel J F; Pereira, Alberto M

2018-01-01

Central serous chorioretinopathy (CSC), a specific form of macular degeneration, has been reported as presenting manifestation of Cushing's syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing's syndrome. It is important to know whether CSC patients should be screened for Cushing's syndrome. Although hypothalamic-pituitary-adrenal (HPA) axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing's syndrome prevalence is increased among chronic CSC (cCSC) patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis. Cross-sectional study. 86 cCSC patients and 24 controls. Prevalence of Cushing's syndrome, HPA axis activity. None of the cCSC patients met the clinical or biochemical criteria of Cushing's syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires. No case of Cushing's syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing's syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

Perceived stress and cognitive function in older adults: which aspect of perceived stress is important?

Science.gov (United States)

Korten, Nicole C M; Comijs, Hannie C; Penninx, Brenda W J H; Deeg, Dorly J H

2017-04-01

Few studies examined the association between perceived stress and cognitive function in older adults. This study will examine which aspects of perceived stress especially impact cognitive function. Cross-sectional data of 1099 older adults between 64 and 100 years from the Longitudinal Aging Study Amsterdam were used. Perceived stress and its subscales perceived helplessness and perceived self-efficacy were measured with the Perceived Stress Scale. Cognitive function was assessed regarding memory, processing speed and executive function. Univariate and multivariate linear regression analyses were performed between the stress measures and the domains of cognitive function. Perceived stress was associated with worse processing speed, direct and delayed recall, semantic fluency and digit span backwards (range β = -0.10; -0.11; p cognitive function, also after adjustment for depressive symptoms or sense of mastery (range β = 0.10; 0.18; p cognitive functions. Perceived self-efficacy might be an important factor in reducing stress and the prevention of cognitive decline. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

[Kennedy V Axis assessment in an Italian outpatient and inpatient population].

Science.gov (United States)

Mundo, Emanuela; Bonalume, Laura; Del Corno, Franco; Madeddu, Fabio; Lang, Margherita

2010-01-01

Kennedy Axis V or K Axis acts is an alternative tool to the DSM-IVTR Global Assessment of Functioning (GAF) Scale, that many researchers describe as a scale with poor inter-rater reliability and clinical utility. Unlike the GAF scale, K Axis provides a multidimensional and multiaxial approach to measure personal, social and interpersonal functioning in psychiatric outpatients and inpatients. In this study, we examined K Axis's inter-raters reliability by using it with an Italian clinical population. Clinicians used Kennedy Axis V to assess global functioning among 180 inpatients, in 9 psychiatric services in Lombardia and Piemonte. Patients were divided into 4 different diagnostic groups, according to the DSM-IV-TR criteria. Intraclass correlations between two independent raters's scores reveal high level of interrater reliability for all K Axis scales (0,633 < ICC < 0,813). Highly significant results in the Kruskal-Wallis test demonstrate that the patient diagnosis influence all the scales scores. Significant differences in patients functioning profiles in all K Axis scales, apart from Violence one, were noted between different diagnosis groups. In this study high level of raters agreement was noted, even if K Axis scales were used in different mental health services from different clinicians. K Axis scales provide a useful profile of patient global functioning, in line with the specific pathology.

Acetyl-L-carnitine (ALC) administration positively affects reproductive axis in hypogonadotropic women with functional hypothalamic amenorrhea.

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Genazzani, A D; Lanzoni, C; Ricchieri, F; Santagni, S; Rattighieri, E; Chierchia, E; Monteleone, P; Jasonni, V M

2011-04-01

Hypothalamic amenorrhea (HA) is characterized by neuroendocrine impairment that, in turn, negatively modulates endocrine function, mainly within the reproductive axis. HA presents with hypo-LH, hypoestrogenism and, until now, a definite therapeutic strategy has not yet been found. The aim of the following study was to test the efficacy of acetyl-L-carnitine (ALC) administration in HA-affected subjects. Twenty-four patients affected by stress-induced HA were divided into two groups according to LH plasma levels: group A, hypo-LH (LH≤3 mIU/ml; no.=16), and group B, normo-LH (LH>3 mIU/ml; no.=8), were treated with ALC (1 g/day, per os) for 16 weeks. Patients underwent baseline hormonal assessment, pulsatility test (for LH and FSH), naloxone test (for LH, FSH and cortisol) both before and after 16 weeks of treatment. Under ALC administration hypo-LH patients showed a significant increase in LH plasma levels (from 1.4±0.3 to 3.1±0.5 mIU/ml, p<0.01) and in LH pulse amplitude (p<0.001). No changes were observed in the normo-LH group. LH response to naloxone was restored under ALC therapy. Maximal LH response and area under the curve under naloxone were significantly increased (p<0.05 and p<0.01, respectively). No changes were observed in the normo-LH patients. Our data support the hypothesis of a specific role of ALC on counteracting the stress-induced abnormalities in hypo-LH patients affected by hypothalamic amenorrhea.

Association of HPA axis hormones with copeptin after psychological stress differs by sex.

Science.gov (United States)

Spanakis, Elias K; Wand, Gary S; Ji, Nan; Golden, Sherita Hill

2016-01-01

Copeptin levels are elevated in severe medical conditions, an effect that is attributed to elevated arginine vasopressin (AVP) levels in response to physiological stress, resulting in activation of hypothalamus-pituitary-adrenal (HPA) axis. In the current study, we wanted to determine if copeptin is responsive to psychological stress, correlates with cortisol and adrenocorticotropin hormone (ACTH), and if associations differed by sex. In a cross-sectional study that included 100 healthy men (41%) and women (59%) (aged 18-30 years; mean 24.6 ± 3 years), who underwent the Trier Social Stress Test (TSST), we examined the association between percent change (peak-baseline/baseline) in copeptin levels and percent change in log ACTH and cortisol. Three baselines samples were drawn followed by blood sampling at 20, 35, 50, 65 and 85 min after TSST. There was a significant positive association between the percent change in copeptin and the percent change in log-transformed salivary cortisol (β-coefficient=0.95; p=0.02). The association between percent change in copeptin and log-transformed serum cortisol was not statistically significant in the overall population. There was a trend for a non-significant association between percent change in copeptin and percent change in log-transformed ACTH (β-coefficient=1.14; p=0.06). In males, there was a significant positive association between the percent change in copeptin levels and log-transformed salivary (β-coefficient=1.33, p=0.016) and serum cortisol (β-coefficient=0.69, p=0.01), whereas in women there was no statistically significant association. We found a significant positive association between percent change in copeptin and percent change in salivary and serum cortisol among males only. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of denial of reward through maternal contact in the neonatal period on adult hypothalamic-pituitary-adrenal axis function in the rat.

Science.gov (United States)

Diamantopoulou, Anastasia; Raftogianni, Androniki; Stamatakis, Antonios; Oitzl, Melly S; Stylianopoulou, Fotini

2013-06-01

Emotional behavioral traits associated with stress response are well documented to be affected by early life events. In the present work, we used a novel paradigm of neonatal experience, in which pups were trained in a T-maze and either received (RER rats) or were denied (DER) the reward of maternal contact, during postnatal days 10-13. We then evaluated stress coping and key factors controlling the function of the hypothalamic-pituitary-adrenal axis in adulthood. Adult male DER rats exposed to a single session of forced swim stress (FSS) showed increased immobility, while RER rats exhibited increased escape attempts. The corticosterone response following this stressor was higher although not prolonged in the DER rats. Their CRH mRNA levels in the PVN were increased up to 2h after the forced swim. However, basal levels of these hormones did not differ among groups. In addition, the DER neonatal experience induced an increase in hippocampal GR but a decrease in CRH-R1 immunopositive cells in the CA1 area of the hippocampus and the central amygdala. Overall, these data show a distinct stress response profile in the DER male rats, characterized by passive coping during the forced swim, increased hormonal response following stress, increased inhibitory control through GR and an indirect contribution of CRH-R1, the latter two factors resulting in a modified regulation of the response termination. It thus appears that DER rats have an enhanced potential for appropriate reactivity upon an incoming challenge, while maintaining in parallel an adequate control of the duration of their stress responses. Copyright © 2012 Elsevier Ltd. All rights reserved.

[The hypothalamic-pituitary-adrenal axis and depressive disorder: recent progress].

Science.gov (United States)

Kunugi, Hiroshi; Hori, Hiroaki; Numakawa, Tadahiro; Ota, Miho

2012-08-01

Depression is a stress-induced disorder and there is compelling evidence for the involvement of hypothalamic-pituitary-adrenal (HPA) axis abnormalities in the disease. Chronic hyperactivity of the HPA axis and resultant excessive glucocorticoid (hypercortisolism) may be causal to depression. We demonstrated that the dexamethasone (DEX)/CRH test is a sensitive state-dependent marker to monitor HPA axis abnormalities. Restoration from HPA axis abnormalities occurs with clinical responses to treatment. Brain-derived neurotrophic factor (BDNF) has also been implicated in depression. We found that glucocorticoid (DEX) suppresses BDNF-induced dendrite outgrowth and synaptic formation via blocking the MAPK pathway in early-developing cultured hippocampal neurons. Furthermore, we demonstrated that glucocorticoid receptor (GR) and TrkB (a specific receptor of BDNF) interact and that DEX acutely suppresses BDNF-induced glutamate release by affecting the PLC-gamma pathway in cultured cortical neurons, indicating a mechanism underlying the effect of excessive glucocorticoid on BDNF function and resultant damage in cortical neurons. In a macroscopic view using magnetic resonance imaging (MRI), we found that individuals with hypercortisolism detected by the DEX/CRH test demonstrated volume loss in gray matter and reduced neural network assessed with diffusion tensor imaging in several brain regions. Finally, we observed that individuals with hypocortisolism detected by the DEX/CRH test tend to present more distress symptoms, maladaptive coping styles, and schizotypal personality traits than their counterparts, which points to the important role of hypocortisolism as well as hypercortisolism in depression spectrum disorders.

Common functional mineralocorticoid receptor polymorphisms modulate the cortisol awakening response : Interaction with SSRIs

NARCIS (Netherlands)

Klok, Melanie D.; Vreeburg, Sophie A.; Penninx, Brenda W. J. H.; Zitman, Frans G.; de Kloet, E. Ron; DeRijk, Roel H.

Background: Cortisol controls the activity of the hypothalamic pituitary adrenal (HPA) axis during stress and during the circadian cycle through central mineralocorticoid (MR) and glucocorticoid receptors (GR). Changes in MR and GR functioning, therefore, may affect HPA axis activity. In this study

Maternal Cortisol Mediates Hypothalamus-Pituitary-Interrenal Axis Development in Zebrafish

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Nesan, Dinushan; Vijayan, Mathilakath M.

2016-01-01

In zebrafish (Danio rerio), de novo synthesis of cortisol in response to stressor exposure commences only after hatch. Maternally deposited cortisol is present during embryogenesis, but a role for this steroid in early development is unclear. We tested the hypothesis that maternal cortisol is essential for the proper development of hypothalamus-pituitary-interrenal (HPI) axis activity and the onset of the stressor-induced cortisol response in larval zebrafish. In this study, zygotic cortisol content was manipulated by microinjecting antibody to sequester this steroid, thereby making it unavailable during embryogenesis. This was compared with embryos containing excess cortisol by microinjection of exogenous steroid. The resulting larval phenotypes revealed distinct treatment effects, including deformed mesoderm structures when maternal cortisol was unavailable and cardiac edema after excess cortisol. Maternal cortisol unavailability heightened the cortisol stress response in post-hatch larvae, whereas excess cortisol abolished the stressor-mediated cortisol elevation. This contrasting hormonal response corresponded with altered expression of key HPI axis genes, including crf, 11B hydroxylase, pomca, and star, which were upregulated in response to reduced cortisol availability and downregulated when embryos had excess cortisol. These findings for the first time underscore a critical role for maternally deposited cortisol in programming HPI axis development and function in zebrafish. PMID:26940285

STRESS AS PREDISPOSING FACTOR OF SOME CHRONIC DISEASES INCLUDING PERIODONTAL DISEASE

Directory of Open Access Journals (Sweden)

Dewi-Nurul M Dewi-Nurul

2006-04-01

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

Cortisol dysregulation: the bidirectional link between stress, depression, and type 2 diabetes mellitus.

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Joseph, Joshua J; Golden, Sherita H

2017-03-01

Controversy exists over the role of stress and depression in the pathophysiology of type 2 diabetes mellitus. Depression has been shown to increase the risk for progressive insulin resistance and incident type 2 diabetes mellitus in multiple studies, whereas the association of stress with diabetes is less clear, owing to differences in study designs and in forms and ascertainment of stress. The biological systems involved in adaptation that mediate the link between stress and physiological functions include the hypothalamic-pituitary-adrenal (HPA) axis and the autonomic nervous and immune systems. The HPA axis is a tightly regulated system that represents one of the body's mechanisms for responding to acute and chronic stress. Depression is associated with cross-sectional and longitudinal alterations in the diurnal cortisol curve, including a blunted cortisol awakening response and flattening of the diurnal cortisol curve. Flattening of the diurnal cortisol curve is also associated with insulin resistance and type 2 diabetes mellitus. In this article, we review and summarize the evidence supporting HPA axis dysregulation as an important biological link between stress, depression, and type 2 diabetes mellitus. © 2016 New York Academy of Sciences.

The stress response and the hypothalamic-pituitary-adrenal axis: from molecule to melancholia.

LENUS (Irish Health Repository)

O'Connor, T M

2012-02-03

Organisms survive by maintaining equilibrium with their environment. The stress system is critical to this homeostasis. Glucocorticoids modulate the stress response at a molecular level by altering gene expression, transcription, and translation, among other pathways. The effect is the inhibition of the functions of inflammatory cells, predominantly mediated through inhibition of cytokines, such as IL-1, IL-6, and TNF-alpha. The central effectors of the stress response are the corticotrophin-releasing hormone (CRH) and locus coeruleus-norepinephrine (LC-NE)\\/sympathetic systems. The CRH system activates the stress response and is subject to modulation by cytokines, hormones, and neurotransmitters. Glucocorticoids also modulate the growth, reproductive and thyroid axes. Abnormalities of stress system activation have been shown in inflammatory diseases such as rheumatoid arthritis, as well as behavioural syndromes such as melancholic depression. These disorders are comparable to those seen in rats whose CRH system is genetically abnormal. Thus, the stress response is central to resistance to inflammatory and behavioural syndromes. In this review, we describe the response to stress at molecular, cellular, neuroendocrine and behavioural levels, and discuss the disease processes that result from a dysregulation of this response, as well as recent developments in their treatment.

Emotional exhaustion and overcommitment to work are differentially associated with hypothalamus-pituitary-adrenal (HPA) axis responses to a low-dose ACTH1-24 (Synacthen) and dexamethasone-CRH test in healthy school teachers.

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Wolfram, Maren; Bellingrath, Silja; Feuerhahn, Nicolas; Kudielka, Brigitte M

2013-01-01

Evidence for a detrimental impact of chronic work stress on health has accumulated in epidemiological research. Recent studies indicate altered hypothalamus-pituitary-adrenal (HPA) axis regulation as a possible biological pathway underlying the link between stress and disease. However, the direction of dysregulation remains unclear, with reported HPA hyper- or hyporeactivity. To disentangle potential effects on different functional levels in the HPA axis, we examined responses using two pharmacological stimulation tests in 53 healthy teachers (31 females, 22 males; mean age: 49.3 years; age range: 30-64 years): a low-dose adrenocorticotrophic hormone (ACTH(1-24), Synacthen) test was used to assess adrenal cortex sensitivity and the combined dexamethasone-corticotropin releasing hormone (DEX-CRH) test to examine pituitary and adrenal cortex reactivity. Blood and saliva samples were collected at - 1,+15,+30,+45,+60,+90,+120 min. Emotional exhaustion (EE), the core dimension of burnout, was measured with the Maslach Burnout Inventory. Overcommitment (OC) was assessed according to Siegrist's effort-reward-imbalance model. We found a significant association between EE and higher plasma cortisol profiles after Synacthen (p = 0.045). By contrast, OC was significantly associated with attenuated ACTH (p = 0.045), plasma cortisol (p = 0.005), and salivary cortisol (p = 0.023) concentrations following DEX-CRH. Results support the notion of altered HPA axis regulation in chronically work-stressed teachers, with differential patterns of hyper- and hyporeactivity depending on individual stress condition and the tested functional level of the HPA axis.

Stress-induced alterations in estradiol sensitivity increase risk for obesity in women.

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Michopoulos, Vasiliki

2016-11-01

The prevalence of obesity in the United States continues to rise, increasing individual vulnerability to an array of adverse health outcomes. One factor that has been implicated causally in the increased accumulation of fat and excess food intake is the activity of the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the face of relentless stressor exposure. However, translational and clinical research continues to understudy the effects sex and gonadal hormones and LHPA axis dysfunction in the etiology of obesity even though women continue to be at greater risk than men for stress-induced disorders, including depression, emotional feeding and obesity. The current review will emphasize the need for sex-specific evaluation of the relationship between stress exposure and LHPA axis activity on individual risk for obesity by summarizing data generated by animal models currently being leveraged to determine the etiology of stress-induced alterations in feeding behavior and metabolism. There exists a clear lack of translational models that have been used to study female-specific risk. One translational model of psychosocial stress exposure that has proven fruitful in elucidating potential mechanisms by which females are at increased risk for stress-induced adverse health outcomes is that of social subordination in socially housed female macaque monkeys. Data from subordinate female monkeys suggest that increased risk for emotional eating and the development of obesity in females may be due to LHPA axis-induced changes in the behavioral and physiological sensitivity of estradiol. The lack in understanding of the mechanisms underlying these alterations necessitate the need to account for the effects of sex and gonadal hormones in the rationale, design, implementation, analysis and interpretation of results in our studies of stress axis function in obesity. Doing so may lead to the identification of novel therapeutic targets with which to combat stress-induced obesity

Stress-stress correlator in ϕ 4 theory: poles or a cut?

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Moore, Guy D.

2018-05-01

We explore the analytical properties of the traceless stress tensor 2-point function at zero momentum and small frequency (relevant for shear viscosity and hydrodynamic response) in hot, weakly coupled λ ϕ 4 theory. We show that, rather than one or a small number of poles, the correlator has a cut along the negative imaginary frequency axis. We briefly discuss this result's relevance for constructing 2'nd order hydrodynamic models of hot relativistic field theories.

A psychology of the human brain–gut–microbiome axis

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Allen, Andrew P.; Dinan, Timothy G.; Clarke, Gerard

2017-01-01

Abstract In recent years, we have seen increasing research within neuroscience and biopsychology on the interactions between the brain, the gastrointestinal tract, the bacteria within the gastrointestinal tract, and the bidirectional relationship between these systems: the brain–gut–microbiome axis. Although research has demonstrated that the gut microbiota can impact upon cognition and a variety of stress‐related behaviours, including those relevant to anxiety and depression, we still do not know how this occurs. A deeper understanding of how psychological development as well as social and cultural factors impact upon the brain–gut–microbiome axis will contextualise the role of the axis in humans and inform psychological interventions that improve health within the brain–gut–microbiome axis. Interventions ostensibly aimed at ameliorating disorders in one part of the brain–gut–microbiome axis (e.g., psychotherapy for depression) may nonetheless impact upon other parts of the axis (e.g., microbiome composition and function), and functional gastrointestinal disorders such as irritable bowel syndrome represent a disorder of the axis, rather than an isolated problem either of psychology or of gastrointestinal function. The discipline of psychology needs to be cognisant of these interactions and can help to inform the future research agenda in this emerging field of research. In this review, we outline the role psychology has to play in understanding the brain–gut–microbiome axis, with a focus on human psychology and the use of research in laboratory animals to model human psychology. PMID:28804508

Left ventricular long axis function assessed during cine-cardiovascular magnetic resonance is an independent predictor of adverse cardiac events.

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Rangarajan, Vibhav; Chacko, Satish Jacob; Romano, Simone; Jue, Jennifer; Jariwala, Nikhil; Chung, Jaehoon; Farzaneh-Far, Afshin

2016-06-07

Left ventricular pump function requires a complex interplay involving myocardial fibers orientated in the longitudinal, oblique and circumferential directions. Long axis dysfunction appears to be an early marker for a number of pathological states. We hypothesized that mitral annular plane systolic excursion (MAPSE) measured during cine-cardiovascular magnetic resonance (CMR) reflects changes in long axis function and may be an early marker for adverse cardiovascular outcomes. The aims of this study were therefore: 1) To assess the feasibility and reproducibility of MAPSE measurements during routine cine-CMR; and 2) To assess whether MAPSE, as a surrogate for long axis function, is a predictor of major adverse cardiovascular events (MACE). Four hundred consecutive patients undergoing CMR were prospectively enrolled. MAPSE was measured in the 4-chamber cine view. Patients were prospectively followed for major adverse cardiac events (MACE) - death, non-fatal myocardial infarction, hospitalization for heart failure or unstable angina, and late revascularization. Cox proportional hazards regression modeling was used to identify factors independently associated with MACE. Net reclassification improvement (NRI) was calculated to assess whether addition of MAPSE resulted in improved risk reclassification of MACE. Seventy-two MACE occurred during a median follow-up of 14.5 months. By Kaplan-Meier analysis, patients with lateral MAPSE cine-CMR is an independent predictor of MACE.

Executive function in cancer patients with posttraumatic stress disorder.

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Yang, Juan; Guo, Juncheng; Jiang, Xiangling

2017-03-01

Background Cancer patients with posttraumatic stress disorder can lead to their noncompliant behaviors. However, less is known about the neurocognitive functioning of posttraumatic stress disorder in general cancer types or patient populations. The current study attempted to examine the prevalence of posttraumatic stress disorder and their relationships with executive function in individuals with cancer. Methods A total of 285 cancer patients with posttraumatic stress disorder and 150 healthy individuals were recruited for the present study. The Clinician Administered PTSD Scale, Tower of Hanoi, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale-Revised Chinese revision were administered to all participants. Results Significant differences in the score of Tower of Hanoi, Wisconsin Card Sorting Test, and Wechsler Adult Intelligence Scale-Revised Chinese revision were observed between the posttraumatic stress disorder group and the healthy control group ( p posttraumatic stress disorder symptoms and executive function. Conclusions These findings suggest that individuals with cancer-related posttraumatic stress disorder exhibit more severe impairment in executive function than healthy controls do.

Associations between circadian and stress response cortisol in children

OpenAIRE

Simons, S.S.H.; Cillessen, A.H.N.; Weerth, C. de

2017-01-01

Hypothalamic-pituitary-adrenal (HPA) axis functioning is characterized by the baseline production of cortisol following a circadian rhythm, as well as by the superimposed production of cortisol in response to a stressor. However, it is relatively unknown whether the basal cortisol circadian rhythm is associated with the cortisol stress response in children. Since alterations in cortisol stress responses have been associated with mental and physical health, this study investigated whether the ...

Effects of resistance exercise on the HPA axis response to psychological stress during short-term smoking abstinence in men.

Science.gov (United States)

Ho, Jen-Yu; Kraemer, William J; Volek, Jeff S; Vingren, Jakob L; Fragala, Maren S; Flanagan, Shawn D; Maladouangdock, Jesse; Szivak, Tunde K; Hatfield, Disa L; Comstock, Brett A; Dunn-Lewis, Courtenay; Ciccolo, Joseph T; Maresh, Carl M

2014-03-01

The purpose of this study was to examine the effects of resistance exercise on the hypothalamic-pituitary-adrenal axis (HPA) response to mental challenge, withdrawal symptoms, urge to smoke, and cognitive stress during 24-hour smoking abstinence. 8 sedentary smokers (mean±SD age: 20.1±1.7y; height: 171.6±10.8cm; body mass: 70.4±12.0kg; smoking history: 2.9±0.8y) completed a 24-hour ad libitum smoking trial (SMO) followed by two 24-hour smoking abstinence trials. During abstinence trials, participants performed six whole body resistance exercises (EX) or a control condition (CON) in the morning, followed by mental challenge tasks in the afternoon. Plasma adrenocorticotropin hormone (ACTH), and salivary and serum cortisol were measured during each visit at rest (REST), and then before (PRE-EX), immediately after (IP-EX), and 30min after exercise (30-EX); and before (PRE-MC), immediately after (IP-MC), and 30min after mental challenge (30-MC). Resistance exercise significantly (p≤0.05) elevated plasma ACTH and serum cortisol at IP-EX during EX compared with SMO and CON trials. Resting ACTH, salivary and serum cortisol concentrations at Pre-MC did not differ between EX and CON trials. The HPA axis response to mental challenge was similar after EX and CON trials. Finally, resistance exercise did not reduce withdrawal symptoms, urge to smoke, or stress. Resistance exercise did not substantially alter resting HPA hormones or the HPA response to mental challenge tasks during 24h of smoking abstinence. © 2013.

Early-life adversity programs emotional functions and the neuroendocrine stress system: the contribution of nutrition, metabolic hormones and epigenetic mechanisms.

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Yam, Kit-Yi; Naninck, Eva F G; Schmidt, Mathias V; Lucassen, Paul J; Korosi, Aniko

2015-01-01

Clinical and pre-clinical studies have shown that early-life adversities, such as abuse or neglect, can increase the vulnerability to develop psychopathologies and cognitive decline later in life. Remarkably, the lasting consequences of stress during this sensitive period on the hypothalamic-pituitary-adrenal axis and emotional function closely resemble the long-term effects of early malnutrition and suggest a possible common pathway mediating these effects. During early-life, brain development is affected by both exogenous factors, like nutrition and maternal care as well as by endogenous modulators including stress hormones. These elements, while mostly considered for their independent actions, clearly do not act alone but rather in a synergistic manner. In order to better understand how the programming by early-life stress takes place, it is important to gain further insight into the exact interplay of these key elements, the possible common pathways as well as the underlying molecular mechanisms that mediate their effects. We here review evidence that exposure to both early-life stress and early-life under-/malnutrition similarly lead to life-long alterations on the neuroendocrine stress system and modify emotional functions. We further discuss how the different key elements of the early-life environment interact and affect one another and next suggest a possible role for the early-life adversity induced alterations in metabolic hormones and nutrient availability in shaping later stress responses and emotional function throughout life, possibly via epigenetic mechanisms. Such knowledge will help to develop intervention strategies, which gives the advantage of viewing the synergistic action of a more complete set of changes induced by early-life adversity.

Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats.

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Sena, Gabriela C; Freitas-Lima, Leandro C; Merlo, Eduardo; Podratz, Priscila L; de Araújo, Julia F P; Brandão, Poliane A A; Carneiro, Maria T W D; Zicker, Marina C; Ferreira, Adaliene V M; Takiya, Christina M; de Lemos Barbosa, Carolina M; Morales, Marcelo M; Santos-Silva, Ana Paula; Miranda-Alves, Leandro; Silva, Ian V; Graceli, Jones B

2017-03-15

Tributyltin chloride (TBT) is a xenobiotic used as a biocide in antifouling paints that has been demonstrated to induce endocrine-disrupting effects, such as obesity and reproductive abnormalities. An integrative metabolic control in the hypothalamus-pituitary-gonadal (HPG) axis was exerted by leptin. However, studies that have investigated the obesogenic TBT effects on the HPG axis are especially rare. We investigated whether metabolic disorders as a result of TBT are correlated with abnormal hypothalamus-pituitary-gonadal (HPG) axis function, as well as kisspeptin (Kiss) action. Female Wistar rats were administered vehicle and TBT (100ng/kg/day) for 15days via gavage. We analyzed their effects on the tin serum and ovary accumulation (as biomarker of TBT exposure), estrous cyclicity, surge LH levels, GnRH expression, Kiss action, fertility, testosterone levels, ovarian apoptosis, uterine inflammation, fibrosis, estrogen negative feedback, body weight gain, insulin, leptin, adiponectin levels, as well as the glucose tolerance (GTT) and insulin sensitivity tests (IST). TBT led to increased serum and ovary tin levels, irregular estrous cyclicity, and decreased surge LH levels, GnRH expression and Kiss responsiveness. A strong negative correlation between the serum and ovary tin levels with lower Kiss responsiveness and GnRH mRNA expression was observed in TBT rats. An increase in the testosterone levels, ovarian and uterine fibrosis, ovarian apoptosis, and uterine inflammation and a decrease in fertility and estrogen negative feedback were demonstrated in the TBT rats. We also identified an increase in the body weight gain and abnormal GTT and IST tests, which were associated with hyperinsulinemia, hyperleptinemia and hypoadiponectinemia, in the TBT rats. TBT disrupted proper functioning of the HPG axis as a result of abnormal Kiss action. The metabolic dysfunctions co-occur with the HPG axis abnormalities. Hyperleptinemia as a result of obesity induced by TBT may be

Cushing’s Syndrome and Hypothalamic–Pituitary–Adrenal Axis Hyperactivity in Chronic Central Serous Chorioretinopathy

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Femke M. van Haalen

2018-02-01

Full Text Available ObjectiveCentral serous chorioretinopathy (CSC, a specific form of macular degeneration, has been reported as presenting manifestation of Cushing’s syndrome. Furthermore, CSC has been associated with both exogenous hypercortisolism and endogenous Cushing’s syndrome. It is important to know whether CSC patients should be screened for Cushing’s syndrome. Although hypothalamic-pituitary-adrenal (HPA axis hyperactivity in CSC has been suggested, no detailed evaluation of the HPA axis has been performed in a large cohort of CSC patients. This study aimed to investigate whether Cushing’s syndrome prevalence is increased among chronic CSC (cCSC patients and whether detailed endocrinological phenotyping indicates hyperactivity of the HPA axis.DesignCross-sectional study.Patients86 cCSC patients and 24 controls.MeasurementsPrevalence of Cushing’s syndrome, HPA axis activity.ResultsNone of the cCSC patients met the clinical or biochemical criteria of Cushing’s syndrome. However, compared to controls, HPA axis activity was increased in cCSC patients, reflected by higher 24 h urinary free cortisol, and accompanying higher waist circumference and diastolic blood pressure, whereas circadian cortisol rhythm and feedback were not different. Chronic CSC patients did not report more stress or stress-related problems on questionnaires.ConclusionNo case of Cushing’s syndrome was revealed in a large cohort of cCSC patients. Therefore, we advise against screening for Cushing’s syndrome in CSC patients, unless additional clinical features are present. However, our results indicate that cCSC is associated with hyperactivity of the HPA axis, albeit not accompanied with perception of more psychosocial stress.

Adaptation of the hypothalamus-pituitary-adrenal axis to daily repeated stress does not follow the rules of habituation: A new perspective.

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Rabasa, Cristina; Gagliano, Humberto; Pastor-Ciurana, Jordi; Fuentes, Silvia; Belda, Xavier; Nadal, Roser; Armario, Antonio

2015-09-01

Repeated exposure to a wide range of stressors differing in nature and intensity results in a reduced response of prototypical stress markers (i.e. plasma levels of ACTH and adrenaline) after an acute challenge with the same (homotypic) stressor. This reduction has been considered to be a habituation-like phenomenon. However, direct experimental evidence for this assumption is scarce. In the present work we demonstrate in adult male rats that adaptation of the hypothalamus-pituitary-adrenal (HPA) axis to repeated stress does not follow some of the critical rules of habituation. Briefly, adaptation was stronger and faster with more severe stressors, maximally observed even with a single exposure to severe stressors, extremely long-lasting, negatively related to the interval between the exposures and positively related to the length of daily exposure. We offer a new theoretical view to explain adaptation to daily repeated stress. Copyright © 2015 Elsevier Ltd. All rights reserved.

Salivary cortisol: a possible biomarker in evaluating stress and effects of interventions in young foster children?

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van Andel, Hans W H; Jansen, Lucres M C; Grietens, Hans; Knorth, Erik J; van der Gaag, Rutger Jan

2014-01-01

Young foster children undergo an early separation from their caregiver(s) and often experience severe stress before placement. However, a considerable part of the children do not show apparent signs of distress, making it difficult for the foster carer to be aware of the amount of stress in their foster child. Potential evidence for using salivary cortisol levels as a dimension to evaluate the amount of stress in young foster children is reviewed. Moreover, the applicability of salivary cortisol in the evaluation of stress-reducing interventions for young foster children is discussed. A systematic review was performed using the databases Medline, Psychinfo, Embase, Ebscohost, and Academic Search Premier. Nine studies were traced in which salivary cortisol was used to measure stress in children placed in family foster care or in adoptive families. Stress in general but also neglect, early loss of a caregiver, a younger age at first placement, and a higher number of placements were associated with an altered hypothalamic-pituitary-adrenal (HPA) axis function in foster children. Moreover, four studies on the effect of stress-reducing interventions on HPA-axis functioning of young foster children were found. These studies suggest that caregiver-based interventions can actually help to normalize the HPA-axis function in foster children, and that such changes co-occur with improved behavioral functioning. Although the results from the papers discussed in this review suggest that diurnal cortisol with a wake up and a bedtime measurement may be a relevant tool to evaluate stress in young foster children, this cannot yet be concluded from the present studies, because statistical data from the studies on foster care and adoption in this review were not robust and researchers used different methods to collect the salivary cortisol. Still, it is noteworthy that all studies did find the same pattern of reduced levels in relation to chronic stress (caused by maltreatment and

Patient specific modeling of the HPA axis related to clinical diagnosis of depression

DEFF Research Database (Denmark)

Bangsgaard, Elisabeth; Ottesen, Johnny T.

2017-01-01

A novel model of the hypothalamic-pituitary-adrenal axis is presented. The axis is an endocrine system responsible for coping with stress and it is likely to be involved in depression. The dynamics of the system is studied and existence, uniqueness and positivity of the solution and the existence...... of an attracting trapping region are proved. The model is calibrated and compared to data for healthy and depressed subjects. A sensitivity analysis resulting in a set of identifiable physiological parameters is provided. A subset is selected for parameter estimation and a reduced version of the model is stated...... and an approximated version is discussed. The model is physiologically based, thus parameters are representative for gland functions or elimination processes. Hence the model may be used for pointing out pathologies by parameter estimation and hypothesis testing whereby it may be used as an objective and refined...

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

Science.gov (United States)

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.

Antagonistic interplay between hypocretin and leptin in the lateral hypothalamus regulates stress responses.

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Bonnavion, Patricia; Jackson, Alexander C; Carter, Matthew E; de Lecea, Luis

2015-02-19

The hypothalamic-pituitary-adrenal (HPA) axis functions to coordinate behavioural and physiological responses to stress in a manner that depends on the behavioural state of the organism. However, the mechanisms through which arousal and metabolic states influence the HPA axis are poorly understood. Here using optogenetic approaches in mice, we show that neurons that produce hypocretin (Hcrt)/orexin in the lateral hypothalamic area (LHA) regulate corticosterone release and a variety of behaviours and physiological hallmarks of the stress response. Interestingly, we found that Hcrt neuronal activity and Hcrt-mediated stress responses were inhibited by the satiety hormone leptin, which acts, in part, through a network of leptin-sensitive neurons in the LHA. These data demonstrate how peripheral metabolic signals interact with hypothalamic neurons to coordinate stress and arousal and suggest one mechanism through which hyperarousal or altered metabolic states may be linked with abnormal stress responses.

miR-181c-BRK1 axis plays a key role in actin cytoskeleton-dependent T cell function.

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Lim, Shok Ping; Ioannou, Nikolaos; Ramsay, Alan G; Darling, David; Gäken, Joop; Mufti, Ghulam J

2018-05-01

MicroRNAs are short endogenous noncoding RNAs that play pivotal roles in a diverse range of cellular processes. The miR-181 family is important in T cell development, proliferation, and activation. In this study, we have identified BRK1 as a potential target of miR-181c using a dual selection functional assay and have showed that miR-181c regulates BRK1 by translational inhibition. Given the importance of miR-181 in T cell function and the potential role of BRK1 in the involvement of WAVE2 complex and actin polymerization in T cells, we therefore investigated the influence of miR-181c-BRK1 axis in T cell function. Stimulation of PBMC derived CD3 + T cells resulted in reduced miR-181c expression and up-regulation of BRK1 protein expression, suggesting that miR-181c-BRK1 axis is important in T cell activation. We further showed that overexpression of miR-181c or suppression of BRK1 resulted in inhibition of T cell activation and actin polymerization coupled with defective lamellipodia generation and immunological synapse formation. Additionally, we found that BRK1 silencing led to reduced expressions of other proteins in the WAVE2 complex, suggesting that the impairment of T cell actin dynamics was a result of the instability of the WAVE2 complex following BRK1 depletion. Collectively, we demonstrated that miR-181c reduces BRK1 protein expression level and highlighted the important role of miR-181c-BRK1 axis in T cell activation and actin polymerization-mediated T cell functions. ©2018 Society for Leukocyte Biology.

Estresse e função reprodutiva feminina Stress and female reproductive function

Directory of Open Access Journals (Sweden)

Simone da Nóbrega Tomaz Moreira

2005-03-01

Full Text Available Este artigo discute a relação do estresse sobre a função reprodutiva, considerando que a infertilidade pode ter causas psicológicas (hipótese da psicogênese ou pode ser a origem do estresse psicológico. A presença do estresse tem o potencial de ativar o eixo hipotálamo-hipófise-adrenal, o qual, inibe o eixo hipotálamo-hipófise-ovariano, levando à paralisação temporária das menstruações. Esse processo pode resultar em infertilidade transitória para as mulheres. Os autores enfatizam a necessidade de uma abordagem psicológica nos serviços de reprodução, objetivando trabalhar as tensões e frustrações advindas da infertilidade e do seu tratamento.This article discusses the relationship between stress and reproduction considering that infertility could bear psychological causes (psychogenesis hypothesis or could be caused by psychological stress. Stress has the potential of activating the hypothalamus-hypophisis-adrenal axis inhibiting the hypothalamus-hypophisis-ovarian axis leading to temporary menstruation paralysis. This process could result in a transitory infertility of women. The authors emphasize the need of a psychological approach in reproduction services with the objective of treating tensions and frustrations derived from infertility and its treatment.

Oxidative Stress/Angiotensinogen/Renin-Angiotensin System Axis in Patients with Diabetic Nephropathy

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Masumi Kamiyama

2013-11-01

Full Text Available Although recent studies have proven that renin-angiotensin system (RAS blockades retard the progression of diabetic nephropathy, the detailed mechanisms of their reno-protective effects on the development of diabetic nephropathy remain uncertain. In rodent models, it has been reported that reactive oxygen species (ROS are important for intrarenal angiotensinogen (AGT augmentation in the progression of diabetic nephropathy. However, no direct evidence is available to demonstrate that AGT expression is enhanced in the kidneys of patients with diabetes. To examine whether the expression levels of ROS- and RAS-related factors in kidneys are increased with the progression of diabetic nephropathy, biopsied samples from 8 controls and 27 patients with type 2 diabetes were used. After the biopsy, these patients were diagnosed with minor glomerular abnormality or diabetes mellitus by clinical and pathological findings. The intensities of AGT, angiotensin II (Ang II, 4-hydroxy-2-nonenal (4-HNE, and heme oxygenase-1 (HO-1 were examined by fluorescence in situ hybridization and/or immunohistochemistry. Expression levels were greater in patients with diabetes than in control subjects. Moreover, the augmented intrarenal AGT mRNA expression paralleled renal dysfunction in patients with diabetes. These data suggest the importance of the activated oxidative stress/AGT/RAS axis in the pathogenesis of diabetic nephropathy.

Better executive function under stress mitigates the effects of recent life stress exposure on health in young adults.

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Shields, Grant S; Moons, Wesley G; Slavich, George M

2017-01-01

Executive function is a neuropsychological construct that enables controlled cognitive processing, which has been hypothesized to enhance individuals' resilience to stress. However, little empirical work has directly examined how executive function under different conditions mitigates the negative effects of stress exposure on health. To address this issue, we recruited 110 healthy young adults and assessed their recent life stress exposure, executive function in either a stressful or non-stressful context, and current health complaints. Based on existing research, we hypothesized that individuals exhibiting better executive function following a laboratory-based stressor (but not a control task) would demonstrate weaker associations between recent stress exposure and health because they perceived recent life stressors as being less severe. Consistent with this hypothesis, better executive function during acute stress, but not in the absence of stress, was associated with an attenuated link between participants' recent life stress exposure and their current health complaints. Moreover, this attenuating effect was mediated by lesser perceptions of stressor severity. Based on these data, we conclude that better executive function under stress is associated with fewer health complaints and that these effects may occur by reducing individuals' perceptions of stressor severity. The data thus suggest the possibility of reducing stress-related health problems by enhancing executive function.

Effects of an Off-Axis Pivoting Elliptical Training Program on Gait Function in Persons With Spastic Cerebral Palsy: A Preliminary Study.

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Tsai, Liang-Ching; Ren, Yupeng; Gaebler-Spira, Deborah J; Revivo, Gadi A; Zhang, Li-Qun

2017-07-01

This preliminary study examined the effects of off-axis elliptical training on reducing transverse-plane gait deviations and improving gait function in 8 individuals with cerebral palsy (CP) (15.5 ± 4.1 years) who completed an training program using a custom-made elliptical trainer that allows transverse-plane pivoting of the footplates during exercise. Lower-extremity off-axis control during elliptical exercise was evaluated by quantifying the root-mean-square and maximal angular displacement of the footplate pivoting angle. Lower-extremity pivoting strength was assessed. Gait function and balance were evaluated using 10-m walk test, 6-minute-walk test, and Pediatric Balance Scale. Toe-in angles during gait were quantified. Participants with CP demonstrated a significant decrease in the pivoting angle (root mean square and maximal angular displacement; effect size, 1.00-2.00) and increase in the lower-extremity pivoting strength (effect size = 0.91-1.09) after training. Reduced 10-m walk test time (11.9 ± 3.7 seconds vs. 10.8 ± 3.0 seconds; P = 0.004; effect size = 1.46), increased Pediatric Balance Scale score (43.6 ± 12.9 vs. 45.6 ± 10.8; P = 0.042; effect size = 0.79), and decreased toe-in angle (3.7 ± 10.5 degrees vs. 0.7 ± 11.7 degrees; P = 0.011; effect size = 1.22) were observed after training. We present an intervention to challenge lower-extremity off-axis control during a weight-bearing and functional activity for individuals with CP. Our preliminary findings suggest that this intervention was effective in enhancing off-axis control, gait function, and balance and reducing in-toeing gait in persons with CP.

Stress and the gut: pathophysiology, clinical consequences, diagnostic approach and treatment options.

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Konturek, Peter C; Brzozowski, T; Konturek, S J

2011-12-01

Stress, which is defined as an acute threat to homeostasis, shows both short- and long-term effects on the functions of the gastrointestinal tract. Exposure to stress results in alterations of the brain-gut interactions ("brain-gut axis") ultimately leading to the development of a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases, food antigen-related adverse responses, peptic ulcer and gastroesophageal reflux disease (GERD). The major effects of stress on gut physiology include: 1) alterations in gastrointestinal motility; 2) increase in visceral perception; 3) changes in gastrointestinal secretion; 4) increase in intestinal permeability; 5) negative effects on regenerative capacity of gastrointestinal mucosa and mucosal blood flow; and 6) negative effects on intestinal microbiota. Mast cells (MC) are important effectors of brain-gut axis that translate the stress signals into the release of a wide range of neurotransmitters and proinflammatory cytokines, which may profoundly affect the gastrointestinal physiology. IBS represents the most important gastrointestinal disorder in humans, and is characterized by chronic or recurrent pain associated with altered bowel motility. The diagnostic testing for IBS patients include routine blood tests, stool tests, celiac disease serology, abdominal sonography, breath testing to rule out carbohydrate (lactose, fructose, etc.) intolerance and small intestinal bacterial overgrowth. Colonoscopy is recommended if alarming symptoms are present or to obtain colonic biopsies especially in patients with diarrhoea predominant IBS. The management of IBS is based on a multifactorial approach and includes pharmacotherapy targeted against the predominant symptom, behavioural and psychological treatment, dietary alterations, education, reassurance and effective patient-physician relationship. When evaluating for the stress

Evidence for Ancestral Programming of Resilience in a Two-Hit Stress Model

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Jamshid Faraji

2017-05-01

Full Text Available In a continuously stressful environment, the effects of recurrent prenatal stress (PS may accumulate across generations and alter stress vulnerability and resilience. Here, we report in female rats that a family history of recurrent ancestral PS facilitates certain aspects of movement performance, and that these benefits are abolished by the experience of a second hit, induced by a silent ischemia during adulthood. Female F4-generation rats with and without a family history of cumulative multigenerational PS (MPS were tested for skilled motor function before and after the induction of a minor ischemic insult by endothelin-1 infusion into the primary motor cortex. MPS resulted in improved skilled motor abilities and blunted hypothalamic-pituitary-adrenal (HPA axis function compared to non-stressed rats. Deep sequencing revealed downregulation of miR-708 in MPS rats along with upregulation of its predicted target genes Mapk10 and Rasd2. Through miR-708 stress may regulate mitogen-activated protein kinase (MAPK pathway activity. Hair trace elemental analysis revealed an increased Na/K ratio, which suggests a chronic shift in adrenal gland function. The ischemic lesion activated the HPA axis in MPS rats only; the lesion, however, abolished the advantage of MPS in skilled reaching. The findings indicate that MPS generates adaptive flexibility in movement, which is challenged by a second stressor, such as a neuropathological condition. Thus, a second “hit” by a stressor may limit behavioral flexibility and neural plasticity associated with ancestral stress.

A low cortisol response to acute stress is related to worse basal memory performance in older people

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Mercedes eAlmela

2014-07-01

Full Text Available Age-related memory decline has been associated with a faulty regulation of the hypothalamus-pituitary-adrenal axis (HPA-axis. The aim of this study was to investigate whether the magnitude of the stress-induced cortisol increase is related to memory performance when memory is measured in non-stressful conditions. To do so, declarative and working memory performance were measured in 31 men and 35 women between 55 and 77 years of age. On a different day, the magnitude of their cortisol response to acute psychosocial stress was measured. The relationship between the cortisol response and memory performance was U shaped: a low cortisol response to stress was related to poorer declarative and working memory performance, whereas those who did not increase their cortisol levels and those who had the largest cortisol increase had better declarative and working memory capabilities. Sex did not moderate these relationships. These results suggest that a low cortisol response to stress could reflect a defective HPA-axis response to stressors that is accompanied by poorer memory performance. Conversely, a high cortisol response seems to reflect a correct functioning of the HPA-axis and may protect against memory deficits in the later stages of human life.

Stress and the Adolescent Brain: Plasticity of Reproductive Behaviors in Female

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Farideh Zafari Zangeneh

2009-03-01

Full Text Available Early life events influence life-long patterns of emotionality and stress responsiveness and alter the rate of brain and body aging.  Much research attention has focused on the programming effects of the hypothalamus pituitary axis (HPA in early life and on understanding HPA function in response to stressors in adulthood. In comparison, there has been relatively little research on adolescence, a time of significant brain development particularly in the frontal lobe and a time which is of great importance for mental and physical health. The hippocampus, amygdala, and prefrontal cortex undergo stress-induced structural remodeling, which alters behavioral and physiological responses. During adolescence, HPA function is characterized by a prolonged activation in response to stressors compared to adulthood, which may render ongoing development of the brain vulnerable. Stress reactivity is markedly influenced by both the pubertal maturation and the experience of the individual. The frequency of the pulses is increased in chronic stress, since the neuroendocrine system is such a good candidate for mediators of many diseases linked to chronic stress. The activity of HPA axis  in life time of female,  sex maturity, pregnancy or lactation is a plasticity of the diurnal rhythm of pulse amplitude; chronic stress can change this program for   formation disorder in behavioral and physiological responses.

A high-order boundary integral method for surface diffusions on elastically stressed axisymmetric rods.

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Li, Xiaofan; Nie, Qing

2009-07-01

Many applications in materials involve surface diffusion of elastically stressed solids. Study of singularity formation and long-time behavior of such solid surfaces requires accurate simulations in both space and time. Here we present a high-order boundary integral method for an elastically stressed solid with axi-symmetry due to surface diffusions. In this method, the boundary integrals for isotropic elasticity in axi-symmetric geometry are approximated through modified alternating quadratures along with an extrapolation technique, leading to an arbitrarily high-order quadrature; in addition, a high-order (temporal) integration factor method, based on explicit representation of the mean curvature, is used to reduce the stability constraint on time-step. To apply this method to a periodic (in axial direction) and axi-symmetric elastically stressed cylinder, we also present a fast and accurate summation method for the periodic Green's functions of isotropic elasticity. Using the high-order boundary integral method, we demonstrate that in absence of elasticity the cylinder surface pinches in finite time at the axis of the symmetry and the universal cone angle of the pinching is found to be consistent with the previous studies based on a self-similar assumption. In the presence of elastic stress, we show that a finite time, geometrical singularity occurs well before the cylindrical solid collapses onto the axis of symmetry, and the angle of the corner singularity on the cylinder surface is also estimated.

Microstructural stress relaxation mechanics in functionally different tendons.

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Screen, H R C; Toorani, S; Shelton, J C

2013-01-01

Tendons experience widely varying loading conditions in vivo. They may be categorised by their function as either positional tendons, which are used for intricate movements and experience lower stress, or as energy storage tendons which act as highly stressed springs during locomotion. Structural and compositional differences between tendons are thought to enable an optimisation of their properties to suit their functional environment. However, little is known about structure-function relationships in tendon. This study adopts porcine flexor and extensor tendon fascicles as examples of high stress and low stress tendons, comparing their mechanical behaviour at the micro-level in order to understand their stress relaxation response. Stress-relaxation was shown to occur predominantly through sliding between collagen fibres. However, in the more highly stressed flexor tendon fascicles, more fibre reorganisation was evident when the tissue was exposed to low strains. By contrast, the low load extensor tendon fascicles appears to have less capacity for fibre reorganisation or shearing than the energy storage tendon, relying more heavily on fibril level relaxation. The extensor fascicles were also unable to sustain loads without rapid and complete stress relaxation. These findings highlight the need to optimise tendon repair solutions for specific tendons, and match tendon properties when using grafts in tendon repairs. Copyright © 2012 IPEM. Published by Elsevier Ltd. All rights reserved.

Neurobiological Interactions Between Stress and the Endocannabinoid System.

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Morena, Maria; Patel, Sachin; Bains, Jaideep S; Hill, Matthew N

2016-01-01

Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes. A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response. In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling have with respect to many of the effects of stress. Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels. Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a downregulation or loss of cannabinoid type 1 (CB1) receptors. With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception, memory and synaptic plasticity. More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and posttraumatic stress disorder. Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.

Exposure to severe stressors causes long-lasting dysregulation of resting and stress-induced activation of the hypothalamic-pituitary-adrenal axis.

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Belda, Xavier; Rotllant, David; Fuentes, Silvia; Delgado, Raúl; Nadal, Roser; Armario, Antonio

2008-12-01

Exposure to some predominantly emotional (electric shock) and systemic (interleukin-1beta) stressors has been found to induce long-term sensitization of the hypothalamic-pituitary-adrenal (HPA) responsiveness to further superimposed stressors. Since exposure to immobilization on wooden boards (IMO) is a severe stressor and may have interest regarding putative animal models of post-traumatic stress disorders (PTSD), we have characterized long-lasting effects of a single exposure to IMO and other stressors on the HPA response to the same (homotypic) and to novel (heterotypic) stressors and the putative mechanisms involved. A single exposure to IMO caused a long-lasting reduction of peripheral and central responses of the HPA axis, likely to be mediated by some brain areas, such as the lateral septum and the medial amygdala. This desensitization is not explained by changes in negative glucocorticoid feedback, and, surprisingly, it is positively related to the intensity of the stressors. In contrast, the HPA response to heterotypic stressors (novel environments) was enhanced, with maximal sensitization on the day after IMO. Sensitization progressively vanished over the course of 1-2 weeks and was not modulated by IMO-induced corticosterone release. Moreover, it could not be explained by changes in the sensitivity of the HPA axis to fast or intermediate/delayed negative feedback, as evaluated 1 week after exposure to IMO, using shock as the heterotypic stressor. Long-lasting stress-induced behavioral changes reminiscent of enhanced anxiety and HPA sensitization are likely to be parallel but partially independent phenomena, the former being apparently not related to the intensity of stressors.

Family history study of the familial coaggregation of borderline personality disorder with axis I and nonborderline dramatic cluster axis II disorders.

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Zanarini, Mary C; Barison, Leah K; Frankenburg, Frances R; Reich, D Bradford; Hudson, James I

2009-08-01

The purpose of this study was to assess the familial coaggregation of borderline personality disorder (BPD) with a full array of axis I disorders and four axis II disorders (antisocial personality disorder, histrionic personality disorder, narcissistic personality disorder, and sadistic personality disorder) in the first-degree relatives of borderline probands and axis II comparison subjects. Four hundred and forty-five inpatients were interviewed about familial psychopathology using the Revised Family History Questionnaire-a semistructured interview of demonstrated reliability. Of these 445 subjects, 341 met both DIB-R and DSM-III-R criteria for BPD and 104 met DSM-III-R criteria for another type of personality disorder (and neither criteria set for BPD). The psychopathology of 1,580 first-degree relatives of borderline probands and 472 relatives of axis II comparison subjects was assessed. Using structural models for familial coaggregation, it was found that BPD coaggregates with major depression, dysthymic disorder, bipolar I disorder, alcohol abuse/dependence, drug abuse/dependence, panic disorder, social phobia, obsessive-compulsive disorder, generalized anxiety disorder, posttraumatic stress disorder, somatoform pain disorder, and all four axis II disorders studied. Taken together, the results of this study suggest that common familial factors, particularly in the areas of affective disturbance and impulsivity, contribute to borderline personality disorder.

Modeling and design of a two-axis elliptical notch flexure hinge

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Wu, Jianwei; Zhang, Yin; Lu, Yunfeng; Wen, Zhongpu; Bin, Deer; Tan, Jiubin

2018-04-01

As an important part of the joule balance system, the two-axis elliptical notch flexure hinge (TENFH) which typically consists of two single-axis elliptical notch flexure hinges was studied. First, a 6 degrees of freedom (6-DOF) compliance model was established based on the coordinate transformation method. In addition, the maximum stress of the TENFH was derived. The compliance and maximum stress model was verified using finite element analysis simulation. To decouple the attitude of the suspended coil system and reduce the offset between the centroid of the suspended coil mechanism and the mass comparator in the joule balance system, a new mechanical structure of TENFH was designed based on the compliance model and stress model proposed in this paper. The maximum rotation range is up to 10°, and the axial load is more than 5 kg, which meets the requirements of the system. The compliance model was also verified by deformation experimentation with the designed TENFH.

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2012-01-01

Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2015-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

NARCIS (Netherlands)

Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

2017-01-01

Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

Effect study of multi-bubbles on stress distribution of fuel particle

International Nuclear Information System (INIS)

Zhao Yi; Wang Xiaomin; Long Chongsheng

2015-01-01

The finite element model was proposed to simulate the process of the UO_2 dispersion fuel particle sustaining the internal pressure of multi-bubbles, and the stress distribution of fuel particle with intra-bubbles was calculated. The results show that when the bubbles line equidistantly along x axis, the max normal stress along y axis increases with the number of bubbles, meanwhile, the increment of the normal stress gradually decreases. There is a limit that the effect of bubble's number imposes on the max normal stress in the fuel particle. When multi-column of bubbles exist, the max normal stress along x axis in the fuel particle increases, and the max normal stress along y axis decreases with the increase of the number of bubble column. The stress concentration in the fuel particle decreases with the spacing radius ratio increasing. (authors)

From Malthus to motive: how the HPA axis engineers the phenotype, yoking needs to wants

NARCIS (Netherlands)

Pecoraro, Norman; Dallman, Mary F.; Warne, James P.; Ginsberg, Abigail B.; Laugero, Kevin D.; la Fleur, Susanne E.; Houshyar, Hani; Gomez, Francisca; Bhargava, Aditi; Akana, Susan F.

2006-01-01

The hypothalamo-pituitary-adrenal (HPA) axis is the critical mediator of the vertebrate stress response system, responding to environmental stressors by maintaining internal homeostasis and coupling the needs of the body to the wants of the mind. The HPA axis has numerous complex drivers and highly

Hypothalamic Pituitary Adrenal Axis Functioning in Reactive and Proactive Aggression in Children

Science.gov (United States)

Lopez-Duran, Nestor L.; Olson, Sheryl L.; Hajal, Nastassia J.; Felt, Barbara T.; Vazquez, Delia M.

2009-01-01

The purpose of this study was to examine the association between hypothalamic-pituitary-adrenal axis (HPA-axis) reactivity and proactive and reactive aggression in pre-pubertal children. After a 30-min controlled base line period, 73 7-year-old children (40 males and 33 females) were randomly assigned to one of two experimental tasks designed to…

Occlusion and brain function: mastication as a prevention of cognitive dysfunction.

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Ono, Y; Yamamoto, T; Kubo, K-ya; Onozuka, M

2010-08-01

Research in animals and humans has shown that mastication maintains cognitive function in the hippocampus, a brain area important for learning and memory. Reduced mastication, an epidemiological risk factor for the development of dementia in humans, attenuates spatial memory and causes hippocampal neurons to deteriorate morphologically and functionally, especially in aged animals. Active mastication rescues the stress-attenuated hippocampal memory process in animals and attenuates the perception of stress in humans by suppressing endocrinological and autonomic stress responses. Active mastication further improves the performance of sustained cognitive tasks by increasing the activation of the hippocampus and the prefrontal cortex, the brain regions that are essential for cognitive processing. Abnormal mastication caused by experimental occlusal disharmony in animals produces chronic stress, which in turn suppresses spatial learning ability. The negative correlation between mastication and corticosteroids has raised the hypothesis that the suppression of the hypothalamic-pituitary-adrenal (HPA) axis by masticatory stimulation contributes, in part, to preserving cognitive functions associated with mastication. In the present review, we examine research pertaining to the mastication-induced amelioration of deficits in cognitive function, its possible relationship with the HPA axis, and the neuronal mechanisms that may be involved in this process in the hippocampus.

Mitochondrial–Lysosomal Axis in Acetaminophen Hepatotoxicity

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Anna Moles

2018-05-01

Full Text Available Acetaminophen (APAP toxicity is the most common cause of acute liver failure and a major indication for liver transplantion in the United States and Europe. Although significant progress has been made in understanding the molecular mechanisms underlying APAP hepatotoxicity, there is still an urgent need to find novel and effective therapies against APAP-induced acute liver failure. Hepatic APAP metabolism results in the production of the reactive metabolite N-acetyl-p-benzoquinone imine (NAPQI, which under physiological conditions is cleared by its conjugation with glutathione (GSH to prevent its targeting to mitochondria. APAP overdose or GSH limitation leads to mitochondrial NAPQI-protein adducts formation, resulting in oxidative stress, mitochondrial dysfunction, and necrotic cell death. As mitochondria are a major target of APAP hepatotoxicity, mitochondrial quality control and clearance of dysfunctional mitochondria through mitophagy, emerges as an important strategy to limit oxidative stress and the engagement of molecular events leading to cell death. Recent evidence has indicated a lysosomal–mitochondrial cross-talk that regulates APAP hepatotoxicity. Moreover, as lysosomal function is essential for mitophagy, impairment in the fusion of lysosomes with autophagosomes-containing mitochondria may compromise the clearance of dysfunctional mitochondria, resulting in exacerbated APAP hepatotoxicity. This review centers on the role of mitochondria in APAP hepatotoxicity and how the mitochondrial/lysosomal axis can influence APAP-induced liver failure.

A smoothing spline that approximates Laplace transform functions only known on measurements on the real axis

International Nuclear Information System (INIS)

D’Amore, L; Campagna, R; Murli, A; Galletti, A; Marcellino, L

2012-01-01

The scientific and application-oriented interest in the Laplace transform and its inversion is testified by more than 1000 publications in the last century. Most of the inversion algorithms available in the literature assume that the Laplace transform function is available everywhere. Unfortunately, such an assumption is not fulfilled in the applications of the Laplace transform. Very often, one only has a finite set of data and one wants to recover an estimate of the inverse Laplace function from that. We propose a fitting model of data. More precisely, given a finite set of measurements on the real axis, arising from an unknown Laplace transform function, we construct a dth degree generalized polynomial smoothing spline, where d = 2m − 1, such that internally to the data interval it is a dth degree polynomial complete smoothing spline minimizing a regularization functional, and outside the data interval, it mimics the Laplace transform asymptotic behavior, i.e. it is a rational or an exponential function (the end behavior model), and at the boundaries of the data set it joins with regularity up to order m − 1, with the end behavior model. We analyze in detail the generalized polynomial smoothing spline of degree d = 3. This choice was motivated by the (ill)conditioning of the numerical computation which strongly depends on the degree of the complete spline. We prove existence and uniqueness of this spline. We derive the approximation error and give a priori and computable bounds of it on the whole real axis. In such a way, the generalized polynomial smoothing spline may be used in any real inversion algorithm to compute an approximation of the inverse Laplace function. Experimental results concerning Laplace transform approximation, numerical inversion of the generalized polynomial smoothing spline and comparisons with the exponential smoothing spline conclude the work. (paper)

Sex, stress, and mood disorders: at the intersection of adrenal and gonadal hormones.

Science.gov (United States)

Fernández-Guasti, A; Fiedler, J L; Herrera, L; Handa, R J

2012-07-01

The risk for neuropsychiatric illnesses has a strong sex bias, and for major depressive disorder (MDD), females show a more than 2-fold greater risk compared to males. Such mood disorders are commonly associated with a dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis. Thus, sex differences in the incidence of MDD may be related with the levels of gonadal steroid hormone in adulthood or during early development as well as with the sex differences in HPA axis function. In rodents, organizational and activational effects of gonadal steroid hormones have been described for the regulation of HPA axis function and, if consistent with humans, this may underlie the increased risk of mood disorders in women. Other developmental factors, such as prenatal stress and prenatal overexposure to glucocorticoids can also impact behaviors and neuroendocrine responses to stress in adulthood and these effects are also reported to occur with sex differences. Similarly, in humans, the clinical benefits of antidepressants are associated with the normalization of the dysregulated HPA axis, and genetic polymorphisms have been found in some genes involved in controlling the stress response. This review examines some potential factors contributing to the sex difference in the risk of affective disorders with a focus on adrenal and gonadal hormones as potential modulators. Genetic and environmental factors that contribute to individual risk for affective disorders are also described. Ultimately, future treatment strategies for depression should consider all of these biological elements in their design. © Georg Thieme Verlag KG Stuttgart · New York.

Prenatal bisphenol a exposure and dysregulation of infant hypothalamic-pituitary-adrenal axis function: findings from the APrON cohort study.

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Giesbrecht, Gerald F; Ejaredar, Maede; Liu, Jiaying; Thomas, Jenna; Letourneau, Nicole; Campbell, Tavis; Martin, Jonathan W; Dewey, Deborah

2017-05-19

Animal models show that prenatal bisphenol A (BPA) exposure leads to sexually dimorphic disruption of the neuroendocrine system in offspring, including the hypothalamic-pituitary-adrenal (HPA) neuroendocrine system, but human data are lacking. In humans, prenatal BPA exposure is associated with sex-specific behavioural problems in children, and HPA axis dysregulation may be a biological mechanism. The objective of the current study was to examine sex differences in associations between prenatal maternal urinary BPA concentration and HPA axis function in 3 month old infants. Mother-infant pairs (n = 132) were part of the Alberta Pregnancy Outcomes and Nutrition study, a longitudinal birth cohort recruited (2010-2012) during pregnancy. Maternal spot urine samples collected during the 2nd trimester were analyzed for total BPA and creatinine. Infant saliva samples collected prior to and after a blood draw were analyzed for cortisol. Linear growth curve models were used to characterize changes in infant cortisol as a function of prenatal BPA exposure. Higher maternal BPA was associated with increases in baseline cortisol among females (β = 0.13 log μg/dL; 95% CI: 0.01, 0.26), but decreases among males (β = -0.22 log μg/dL; 95% CI: -0.39, -0.05). In contrast, higher BPA was associated with increased reactivity in males (β = .30 log μg/dL; 95% CI: 0.04, 0.56) but decreased reactivity in females (β = -0.15 log μg/dL; 95% CI: -0.35, 0.05). Models adjusting for creatinine yielded similar results. Prenatal BPA exposure is associated with sex-specific changes in infant HPA axis function. The biological plausibility of these findings is supported by their consistency with evidence in rodent models. Furthermore, these data support the hypotheses that sexually dimorphic changes in children's behaviour following prenatal BPA exposure are mediated by sexually dimorphic changes in HPA axis function.

Irritable bowel syndrome, the microbiota and the gut-brain axis

DEFF Research Database (Denmark)

Raskov, Hans; Burcharth, Jakob; Pommergaard, Hans-Christian

2016-01-01

Irritable bowel syndrome is a common functional gastrointestinal disorder and it is now evident that irritable bowel syndrome is a multi-factorial complex of changes in microbiota and immunology. The bidirectional neurohumoral integrated communication between the microbiota and the autonomous...... nervous system is called the gut-brain-axis, which integrates brain and GI functions, such as gut motility, appetite and weight. The gut-brain-axis has a central function in the perpetuation of irritable bowel syndrome and the microbiota plays a critical role. The purpose of this article is to review...... recent research concerning the epidemiology of irritable bowel syndrome, influence of microbiota, probiota, gut-brain-axis, and possible treatment modalities on irritable bowel syndrome....

Obesity and the hypothalamic-pituitary-adrenal axis in adolescent girls.

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Hillman, Jennifer B; Dorn, Lorah D; Loucks, Tammy L; Berga, Sarah L

2012-03-01

Stress and stress-related concomitants, including hypothalamic-pituitary-adrenal (HPA) axis activation, are implicated in obesity and its attendant comorbidities. Little is known about this relationship in adolescents. To begin to address this important knowledge gap, we studied HPA axis activity in 262 healthy adolescent girls aged 11, 13, 15, and 17 years. We hypothesized that obesity would be correlated with increased HPA axis activity and reactivity. Measures of HPA axis activity included 3 blood samples obtained midday (between 1:00 and 2:00 pm) over the course of 40 minutes; overnight urine free cortisol; and cortisol levels 0, 20, and 40 minutes after venipuncture (cortisol reactivity). Measures of adiposity included body mass index (BMI), BMI z score (BMI-Z), percentage body fat, and fat distribution (central adiposity) assessed by dual-energy x-ray absorptiometry. Daytime levels of serum cortisol were inversely associated with BMI-Z and central adiposity (P cortisol excretion rate was positively correlated with BMI, BMI-Z, and central adiposity. There was blunting of cortisol response to venipuncture with increasing adiposity. Our results suggest that there may be reduced cortisol levels during the day and increased levels at night with increasing degree of adiposity. This study provides preliminary findings indicating an alteration of the circadian rhythm of cortisol with obesity. We conclude that obesity is associated with altered HPA activity in adolescent girls. The clinical implications of our findings require further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

HPA axis hyperactivity as suicide predictor in elderly mood disorder inpatients.

Science.gov (United States)

Jokinen, Jussi; Nordström, Peter

2008-11-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis function is associated with suicidal behaviour and age-associated alterations in HPA axis functioning may render elderly individuals more susceptible to HPA dysregulation related to mood disorders. Research on HPA axis function in suicide prediction in elderly mood disorder patients is sparse. The study sample consisted of 99 depressed elderly inpatients 65 years of age or older admitted to the department of Psychiatry at the Karolinska University Hospital between 1980 and 2000. The hypothesis was that elderly mood disorder inpatients who fail to suppress cortisol in the dexamethasone suppression test (DST) are at higher risk of suicide. The DST non-suppression distinguished between suicides and survivors in elderly depressed inpatients and the suicide attempt at the index episode was a strong predictor for suicide. Additionally, the DST non-suppression showed higher specificity and predictive value in the suicide attempter group. Due to age-associated alterations in HPA axis functioning, the optimal cut-off for DST non-suppression in suicide prediction may be higher in elderly mood disorder inpatients. These data demonstrate the importance of attempted suicide and DST non-suppression as predictors of suicide risk in late-life depression and suggest the use for neuroendocrine testing of HPA axis functioning as a complementary tool in suicide prevention.

Magnetic property variation in carbon steel and chrome-molybdenum steel as a function of uniaxial stress noncoaxial with the magnetic field (abstract)

International Nuclear Information System (INIS)

Sablik, M.J.; Kaminski, D.A.; Jiles, D.C.; Biner, S.B.

1993-01-01

Magnescope 1 magnetic measurements were made on carbon steel specimens ranging from 0.1--0.8 wt %C and on chrome-molybdenum steel specimens cut from electric power plant pipes previously in service. The carbon steel specimens were heat-treated using three procedures: (1) spheroidization, (2) quenching, and (3) quench and tempering. The specimens were subjected to uniaxial tension up to 40 ksi. The inspection head was aligned so that the magnetic field was oriented at different angles with respect to the stress axis. Magnetic properties (such as coercivity and maximum differential permeability) were extracted from digitized magnetic hysteresis loop measurements. Magnetic properties were studied as a function of stress at each angle of stress-field orientation. To our knowledge, such a comprehensive study of noncoaxial stress and field effects has never been accomplished before for such a wide variety of steel specimens. Results for the various materials are presented for different orientation angles and compared to numerical results from the noncoaxial magnetomechanical hysteresis model of Sablik et al. 2

Prenatal stress alters amygdala functional connectivity in preterm neonates.

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Scheinost, Dustin; Kwon, Soo Hyun; Lacadie, Cheryl; Sze, Gordon; Sinha, Rajita; Constable, R Todd; Ment, Laura R

2016-01-01

Exposure to prenatal and early-life stress results in alterations in neural connectivity and an increased risk for neuropsychiatric disorders. In particular, alterations in amygdala connectivity have emerged as a common effect across several recent studies. However, the impact of prenatal stress exposure on the functional organization of the amygdala has yet to be explored in the prematurely-born, a population at high risk for neuropsychiatric disorders. We test the hypothesis that preterm birth and prenatal exposure to maternal stress alter functional connectivity of the amygdala using two independent cohorts. The first cohort is used to establish the effects of preterm birth and consists of 12 very preterm neonates and 25 term controls, all without prenatal stress exposure. The second is analyzed to establish the effects of prenatal stress exposure and consists of 16 extremely preterm neonates with prenatal stress exposure and 10 extremely preterm neonates with no known prenatal stress exposure. Standard resting-state functional magnetic resonance imaging and seed connectivity methods are used. When compared to term controls, very preterm neonates show significantly reduced connectivity between the amygdala and the thalamus, the hypothalamus, the brainstem, and the insula (p amygdala and the thalamus, the hypothalamus, and the peristriate cortex (p amygdala connectivity associated with preterm birth. Functional connectivity from the amygdala to other subcortical regions is decreased in preterm neonates compared to term controls. In addition, these data, for the first time, suggest that prenatal stress exposure amplifies these decreases.

A self-medication hypothesis for increased vulnerability to drug abuse in prenatally restraint stressed rats.

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Reynaert, Marie-Line; Marrocco, Jordan; Gatta, Eleonora; Mairesse, Jérôme; Van Camp, Gilles; Fagioli, Francesca; Maccari, Stefania; Nicoletti, Ferdinando; Morley-Fletcher, Sara

Stress-related events that occur in the perinatal period can permanently change brain and behavior of the developing individual and there is increasing evidence that early-life adversity is a contributing factor in the etiology of drug abuse and mood disorders. Neural adaptations resulting from early-life stress may mediate individual differences in novelty responsiveness and in turn contribute to drug abuse vulnerability. Prenatal restraint stress (PRS) in rats is a well-documented model of early stress known to induce long-lasting neurobiological and behavioral alterations including impaired feedback mechanisms of the HPA axis, enhanced novelty seeking, and increased sensitiveness to psychostimulants as well as anxiety/depression-like behavior. Together with the HPA axis, functional alterations of the mesolimbic dopamine system and of the metabotropic glutamate receptors system appear to be involved in the addiction-like profile of PRS rats.

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study.

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Aydemir, Ömer; Çubukçuoğlu, Zeynep; Erdin, Soner; Taş, Cumhur; Onur, Ece; Berk, Michael

2014-01-01

This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502); household activities and superoxide dismutase (r = 0.501); participation in social activities and nitric oxide (r = 0.414); hobbies and leisure time activities and total glutathione (r = -0.567), superoxide dismutase (r = 0.667), and neurotrophin 4 (r = 0.450); and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597). There was no correlation between other domains of psychosocial functioning and oxidative stress markers. These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

Oxidative stress markers, cognitive functions, and psychosocial functioning in bipolar disorder: an empirical cross-sectional study

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Ömer Aydemir

2014-12-01

Full Text Available Objective: This study aimed to evaluate the relationship between oxidative stress markers and cognitive functions and domains of psychosocial functioning in bipolar disorder. Methods: Oxidative stress markers, cognitive functions, and domains of psychosocial functioning were evaluated in 51 patients with bipolar disorder who were in remission. Correlation analyses between these parameters were calculated with data controlled for duration of illness and number of episodes. Results: There was no statistically significant correlation between oxidative stress markers and cognitive functions. In terms of psychosocial functioning, significant correlations were found between malondialdehyde and sense of stigmatization (r = -0.502; household activities and superoxide dismutase (r = 0.501; participation in social activities and nitric oxide (r = 0.414; hobbies and leisure time activities and total glutathione (r = -0.567, superoxide dismutase (r = 0.667, and neurotrophin 4 (r = 0.450; and taking initiative and self-sufficiency and superoxide dismutase (r = 0.597. There was no correlation between other domains of psychosocial functioning and oxidative stress markers. Conclusion: These results imply that oxidative stress markers do not appear to correlate clearly with cognitive impairment and reduced psychosocial functioning. However, there were some associations between selected oxidative markers and activity-oriented functional markers. This may represent a true negative association, or may be an artifact of oxidative stress being a state rather than a trait marker.

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

Directory of Open Access Journals (Sweden)

Li-Li Wu

2016-01-01

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

Gut-Microbiota-Brain Axis and Its Effect on Neuropsychiatric Disorders With Suspected Immune Dysregulation.

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Petra, Anastasia I; Panagiotidou, Smaro; Hatziagelaki, Erifili; Stewart, Julia M; Conti, Pio; Theoharides, Theoharis C

2015-05-01

Gut microbiota regulate intestinal function and health. However, mounting evidence indicates that they can also influence the immune and nervous systems and vice versa. This article reviews the bidirectional relationship between the gut microbiota and the brain, termed the microbiota-gut-brain (MGB) axis, and discusses how it contributes to the pathogenesis of certain disorders that may involve brain inflammation. Articles were identified with a search of Medline (starting in 1980) by using the key words anxiety, attention-deficit hypersensitivity disorder (ADHD), autism, cytokines, depression, gut, hypothalamic-pituitary-adrenal (HPA) axis, inflammation, immune system, microbiota, nervous system, neurologic, neurotransmitters, neuroimmune conditions, psychiatric, and stress. Various afferent or efferent pathways are involved in the MGB axis. Antibiotics, environmental and infectious agents, intestinal neurotransmitters/neuromodulators, sensory vagal fibers, cytokines, and essential metabolites all convey information to the central nervous system about the intestinal state. Conversely, the hypothalamic-pituitary-adrenal axis, the central nervous system regulatory areas of satiety, and neuropeptides released from sensory nerve fibers affect the gut microbiota composition directly or through nutrient availability. Such interactions seem to influence the pathogenesis of a number of disorders in which inflammation is implicated, such as mood disorder, autism-spectrum disorders, attention-deficit hypersensitivity disorder, multiple sclerosis, and obesity. Recognition of the relationship between the MGB axis and the neuroimmune systems provides a novel approach for better understanding and management of these disorders. Appropriate preventive measures early in life or corrective measures such as use of psychobiotics, fecal microbiota transplantation, and flavonoids are discussed. Copyright © 2015 Elsevier HS Journals, Inc. All rights reserved.

Personality traits in rats predict vulnerability and resilience to developing stress-induced depression-like behaviors, HPA axis hyper-reactivity and brain changes in pERK1/2 activity

DEFF Research Database (Denmark)

Castro, Jorge E; Diessler, Shanaz; Varea, Emilio

2012-01-01

Emerging evidence indicates that certain behavioral traits, such as anxiety, are associated with the development of depression-like behaviors after exposure to chronic stress. However, single traits do not explain the wide variability in vulnerability to stress observed in outbred populations. We...... hypothesized that a combination of behavioral traits might provide a better characterization of an individual's vulnerability to prolonged stress. Here, we sought to determine whether the characterization of relevant behavioral traits in rats could aid in identifying individuals with different vulnerabilities...... to developing stress-induced depression-like behavioral alterations. We also investigated whether behavioral traits would be related to the development of alterations in the hypothalamic-pituitary-adrenal axis and in brain activity - as measured through phosphorylation of extracellular signal-regulated kinase 1...

Mastication as a Stress-Coping Behavior.

Science.gov (United States)

Kubo, Kin-ya; Iinuma, Mitsuo; Chen, Huayue

2015-01-01

Exposure to chronic stress induces various physical and mental effects that may ultimately lead to disease. Stress-related disease has become a global health problem. Mastication (chewing) is an effective behavior for coping with stress, likely due to the alterations chewing causes in the activity of the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Mastication under stressful conditions attenuates stress-induced increases in plasma corticosterone and catecholamines, as well as the expression of stress-related substances, such as neurotrophic factors and nitric oxide. Further, chewing reduces stress-induced changes in central nervous system morphology, especially in the hippocampus and hypothalamus. In rodents, chewing or biting on wooden sticks during exposure to various stressors reduces stress-induced gastric ulcer formation and attenuates spatial cognitive dysfunction, anxiety-like behavior, and bone loss. In humans, some studies demonstrate that chewing gum during exposure to stress decreases plasma and salivary cortisol levels and reduces mental stress, although other studies report no such effect. Here, we discuss the neuronal mechanisms that underline the interactions between masticatory function and stress-coping behaviors in animals and humans.

Regulatory landscape of AGE-RAGE-oxidative stress axis and its modulation by PPARγ activation in high fructose diet-induced metabolic syndrome.

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Cannizzaro, Luca; Rossoni, Giuseppe; Savi, Federica; Altomare, Alessandra; Marinello, Cristina; Saethang, Thammakorn; Carini, Marina; Payne, D Michael; Pisitkun, Trairak; Aldini, Giancarlo; Leelahavanichkul, Asada

2017-01-01

The AGE-RAGE-oxidative stress (AROS) axis is involved in the onset and progression of metabolic syndrome induced by a high-fructose diet (HFD). PPARγ activation is known to modulate metabolic syndrome; however a systems-level investigation looking at the protective effects of PPARγ activation as related to the AROS axis has not been performed. The aim of this work is to simultaneously characterize multiple molecular parameters within the AROS axis, using samples taken from different body fluids and tissues of a rat model of HFD-induced metabolic syndrome, in the presence or absence of a PPARγ agonist, Rosiglitazone (RGZ). Rats were fed with 60% HFD for the first half of the treatment duration (21 days) then continued with either HFD alone or HFD plus RGZ for the second half. Rats receiving HFD alone showed metabolic syndrome manifestations including hypertension, dyslipidemia, increased glucose levels and insulin resistance, as well as abnormal kidney and inflammatory parameters. Systolic blood pressure, plasma triglyceride and glucose levels, plasma creatinine, and albuminuria were significantly improved in the presence of RGZ. The following molecular parameters of the AROS axis were significantly upregulated in our rat model: carboxymethyl lysine (CML) in urine and liver; carboxyethyl lysine (CEL) in urine; advanced glycation end products (AGEs) in plasma; receptor for advanced glycation end products (RAGE) in liver and kidney; advanced oxidation protein products (AOPP) in plasma; and 4-hydroxynonenal (HNE) in plasma, liver, and kidney. Conversely, with RGZ administration, the upregulation of AOPP and AGEs in plasma, CML and CEL in urine, RAGE in liver as well as HNE in plasma and liver was significantly counteracted/prevented. Our data demonstrate (i) the systems-level regulatory landscape of HFD-induced metabolic syndrome involving multiple molecular parameters, including HNE, AGEs and their receptor RAGE, and (ii) attenuation of metabolic syndrome by

Suicidal behavior on Axis VI: clinical data supporting a sixth Axis for DSM-V.

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Van Orden, Kimberly A; Witte, Tracy K; Holm-Denoma, Jill; Gordon, Kathryn H; Joiner, Thomas E

2011-01-01

Oquendo and colleagues (Oquendo, Baca-García, Mann, & Giner, 2008; Oquendo & Currier, 2009) recommend that DSM-V emphasize suicide risk assessment on a sixth axis, thereby increasing regularity of suicide risk assessments. We propose that evidence of nonredundancy with Axis V - Global Assessment of Functioning (GAF) is one piece of data that can serve as a starting point for a line of research establishing incremental predictive utility for a separate suicide risk assessment in the DSM framework. A standardized suicide risk assessment protocol, measures of depressive, anxious, and eating disordered symptomatology, as well as an index of comorbidity were administered to a sample of 412 adult outpatients. Our data indicate that data from standardized suicide risk assessments are associated with indices of symptomatology severity as well as comorbidity, controlling for GAF. These results support the nonredundancy of the assessments and suggest the utility of longitudinal investigations of the predictive utility of a sixth DSM axis in the assessment of suicide risk.

Boosting recovery rather than buffering reactivity: Higher stress-induced oxytocin secretion is associated with increased cortisol reactivity and faster vagal recovery after acute psychosocial stress.

Science.gov (United States)

Engert, Veronika; Koester, Anna M; Riepenhausen, Antje; Singer, Tania

2016-12-01

Animal models and human studies using paradigms designed to stimulate endogenous oxytocin release suggest a stress-buffering role of oxytocin. We here examined the involvement of stress-induced peripheral oxytocin secretion in reactivity and recovery phases of the human psychosocial stress response. Healthy male and female participants (N=114) were subjected to a standardized laboratory stressor, the Trier Social Stress Test. In addition to plasma oxytocin, cortisol was assessed as a marker of hypothalamic-pituitary-adrenal (HPA-) axis activity, alpha-amylase and heart rate as markers of sympathetic activity, high frequency heart rate variability as a marker of vagal tone and self-rated anxiety as an indicator of subjective stress experience. On average, oxytocin levels increased by 51% following psychosocial stress. The stress-induced oxytocin secretion, however, did not reduce stress reactivity. To the contrary, higher oxytocin secretion was associated with greater cortisol reactivity and peak cortisol levels in both sexes. In the second phase of the stress response the opposite pattern was observed, with higher oxytocin secretion associated with faster vagal recovery. We suggest that after an early stage of oxytocin and HPA-axis co-activation, the stress-reducing action of oxytocin unfolds. Due to the time lag it manifests as a recovery-boosting rather than a reactivity-buffering effect. By reinforcing parasympathetic autonomic activity, specifically during stress recovery, oxytocin may provide an important protective function against the health-compromising effects of sustained stress. Copyright © 2016 Elsevier Ltd. All rights reserved.

Frequency and Wavevector Dependence of the Atomic Level Stress-Stress Correlation Function in a Model Supercooled Liquid

Science.gov (United States)

Levashov, Valentin A.; Morris, James R.; Egami, Takeshi

2012-02-01

Temporal and spatial correlations among the local atomic level shear stresses were studied for a model liquid iron by molecular dynamics simulation [PRL 106,115703]. Integration over time and space of the shear stress correlation function F(r,t) yields viscosity via Green-Kubo relation. The stress correlation function in time and space F(r,t) was Fourier transformed to study the dependence on frequency, E, and wave vector, Q. The results, F(Q,E), showed damped shear stress waves propagating in the liquid for small Q at high and low temperatures. We also observed additional diffuse feature that appears as temperature is reduced below crossover temperature of potential energy landscape at relatively low frequencies at small Q. We suggest that this additional feature might be related to dynamic heterogeneity and boson peaks. We also discuss a relation between the time-scale of the stress-stress correlation function and the alpha-relaxation time of the intermediate self-scattering function S(Q,E).

Prenatal Maternal Stress Predicts Methylation of Genes Regulating the Hypothalamic-Pituitary-Adrenocortical System in Mothers and Newborns in the Democratic Republic of Congo

Science.gov (United States)

Kertes, Darlene A.; Kamin, Hayley S.; Hughes, David A.; Rodney, Nicole C.; Bhatt, Samarth; Mulligan, Connie J.

2016-01-01

Exposure to stress early in life permanently shapes activity of the hypothalamic-pituitary-adrenocortical (HPA) axis and the brain. Prenatally, glucocorticoids pass through the placenta to the fetus with postnatal impacts on brain development, birth weight (BW), and HPA axis functioning. Little is known about the biological mechanisms by which…

Effects of work stress and home stress on autonomic nervous function in Japanese male workers.

Science.gov (United States)

Maeda, Eri; Iwata, Toyoto; Murata, Katsuyuki

2015-01-01

Autonomic imbalance is one of the important pathways through which psychological stress contributes to cardiovascular diseases/sudden death. Although previous studies have focused mainly on stress at work (work stress), the association between autonomic function and stress at home (home stress) is still poorly understood. The purpose was to clarify the effect of work/home stress on autonomic function in 1,809 Japanese male workers. We measured corrected QT (QTc) interval and QT index on the electrocardiogram along with blood pressure and heart rate. Participants provided self-reported information about the presence/absence of work/home stress and the possible confounders affecting QT indicators. Home stress was related positively to QT index (p=0.040) after adjusting for the possible confounders, though work stress did not show a significant relation to QTc interval or QT index. The odds ratio of home stress to elevated QT index (≥105) was 2.677 (95% CI, 1.050 to 6.822). Work/home stress showed no significant relation to blood pressure or heart rate. These findings suggest that autonomic imbalance, readily assessed by QT indicators, can be induced by home stress in Japanese workers. Additional research is needed to identify different types of home stress that are strongly associated with autonomic imbalance.

Stress og hjerte-kar-sygdom

DEFF Research Database (Denmark)

Ebstrup, Jeanette Frost; Jørgensen, Torben

2012-01-01

and hypothalamic-pituitary-adrenal axis) are also found. Personality and general coping resources influence stress-appraisal, stress-coping and stress-response. Future studies should integrate stress as a cause (stressor), as a subjective reaction (perception), and as a physiological reaction in the same...

Role of the Hypothalamic-Pituitary-Adrenal Axis in Developmental Programming of Health and Disease

Science.gov (United States)

Xiong, Fuxia; Zhang, Lubo

2012-01-01

Adverse environments during the fetal and neonatal development period may permanently program physiology and metabolism, and lead to increased risk of diseases in later life. Programming of the hypothalamic-pituitary-adrenal (HPA) axis is one of the key mechanisms that contribute to altered metabolism and response to stress. Programming of the HPA axis often involves epigenetic modification of the glucocorticoid receptor (GR) gene promoter, which influences tissue-specific GR expression patterns and response to stimuli. This review summarizes the current state of research on the HPA axis and programming of health and disease in the adult, focusing on the epigenetic regulation of GR gene expression patterns in response to fetal and neonatal stress. Aberrant GR gene expression patterns in the developing brain may have a significant negative impact on protection of the immature brain against hypoxic-ischemic encephalopathy in the critical period of development during and immediately after birth. PMID:23200813

Weight functions for the determination of stress intensity factor and T-stress for edge-cracked plates with built-in ends

International Nuclear Information System (INIS)

Li, J.; Wang, X.; Tan, C.L.

2004-01-01

This paper presents the weight functions for the determination of the stress intensity factor and T-stress solutions for edge-cracked plates with built-in ends under complex stress distributions. First, a compliance analysis approach is used to calculate stress intensity factor and T-stress for edge cracks in finite width plates with built-in ends with uniform or linear stress distributions acting on the crack face. The results serve as the reference solutions for the next step in which the approaches of deriving weight functions from reference stress intensity factor and T-stress solutions developed for stress boundary conditions are extended to obtain the corresponding weight functions for edge-cracked plates with built-in ends. Finite element analysis is conducted to validate the derived solutions. The weight functions derived are suitable for obtaining stress intensity factors and T-stress solutions under any complex stress field

Influence of Stress Shape Function on Analysis of Contact Problem Using Hybrid Photoelasticity

International Nuclear Information System (INIS)

Shin, Dongchul; Hawong, Jaisug

2013-01-01

In this research, a study on stress shape functions was conducted to analyze the contact stress problem by using a hybrid photoelasticity. Because the contact stress problem is generally solved as a half-plane problem, the relationship between two analytical stress functions, which are compositions of the Airy stress function, was similar to one of the crack problem. However, this relationship in itself could not be used to solve the contact stress problem (especially one with singular points). Therefore, to analyze the contact stress problem more correctly, stress shape functions based on the condition of two contact end points had to be considered in the form of these two analytical stress functions. The four types of stress shape functions were related to the stress singularities at the two contact end points. Among them, the primary two types used for the analysis of an O-ring were selected, and their validities were verified in this work

The somatotropic axis: Effects on brain and cognitive functions

NARCIS (Netherlands)

Quik, E.H.

2012-01-01

Both hormones of the somatotropic axis, insulin-like growth factor-1 (IGF-1) and growth hormone (GH) can cross the blood-brain barrier and bind to their receptors in neurons and glia throughout the brain. Features of aging resemble those of GHD and aging is also associated with a decline in the

Analytical Calculation of D- and Q-axis Inductance for Interior Permanent Magnet Motors Based on Winding Function Theory

Directory of Open Access Journals (Sweden)

Peixin Liang

2016-07-01

Full Text Available Interior permanent magnet (IPM motors are widely used in electric vehicles (EVs, benefiting from the excellent advantages of a more rational use of energy. For further improvement of energy utilization, this paper presents an analytical method of d- and q-axis inductance calculation for IPM motors with V-shaped rotor in no-load condition. A lumped parameter magnetic circuit model (LPMCM is adopted to investigate the saturation and nonlinearity of the bridge. Taking into account the influence of magnetic field distribution on inductance, the winding function theory (WFT is employed to accurately calculate the armature reaction airgap magnetic field and d- and q-axis inductances. The validity of the analytical technique is verified by the finite element method (FEM.

Nutrient restriction induces failure of reproductive function and molecular changes in hypothalamus-pituitary-gonadal axis in postpubertal gilts.

Science.gov (United States)

Zhou, Dongsheng; Zhuo, Yong; Che, Lianqiang; Lin, Yan; Fang, Zhengfeng; Wu, De

2014-07-01

People on a diet to lose weight may be at risk of reproductive failure. To investigate the effects of nutrient restriction on reproductive function and the underlying mechanism, changes of reproductive traits, hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis were examined in postpubertal gilts at anestrus induced by nutrient restriction. Gilts having experienced two estrus cycles were fed a normal (CON, 2.86 kg/d) or nutrient restricted (NR, 1 kg/d) food regimens to expect anestrus. NR gilts experienced another three estrus cycles, but did not express estrus symptoms at the anticipated fourth estrus. Blood samples were collected at 5 days' interval for consecutive three times for measurement of hormone concentrations at the 23th day of the fourth estrus cycle. Individual progesterone concentrations of NR gilts from three consecutive blood samples were below 1.0 ng/mL versus 2.0 ng/mL in CON gilts, which was considered anestrus. NR gilts had impaired development of reproductive tract characterized by absence of large follicles (diameter ≥ 6 mm), decreased number of corepus lutea and atrophy of uterus and ovary tissues. Circulating concentrations of IGF-I, kisspeptin, estradiol, progesterone and leptin were significantly lower in NR gilts than that in CON gilts. Nutrient restriction down-regulated gene expressions of kiss-1, G-protein coupled protein 54, gonadotropin-releasing hormone, estrogen receptor α, progesterone receptor, leptin receptor, follicle-stimulating hormone and luteinizing hormone and insulin-like growth factor I in hypothalamus-pituitary-gonadal axis of gilts. Collectively, nutrient restriction resulted in impairment of reproductive function and changes of hormone secretions and gene expressions in hypothalamus-pituitary-gonadal axis, which shed light on the underlying mechanism by which nutrient restriction influenced reproductive function.

Germ Cell Origins of Posttraumatic Stress Disorder Risk: The Transgenerational Impact of Parental Stress Experience.

Science.gov (United States)

Rodgers, Ali B; Bale, Tracy L

2015-09-01

Altered stress reactivity is a predominant feature of posttraumatic stress disorder (PTSD) and may reflect disease vulnerability, increasing the probability that an individual will develop PTSD following trauma exposure. Environmental factors, particularly prior stress history, contribute to the developmental programming of the hypothalamic-pituitary-adrenal stress axis. Critically, the consequences of stress experiences are transgenerational, with parental stress exposure impacting stress reactivity and PTSD risk in subsequent generations. Potential molecular mechanisms underlying this transmission have been explored in rodent models that specifically examine the paternal lineage, identifying epigenetic signatures in male germ cells as possible substrates of transgenerational programming. Here, we review the role of these germ cell epigenetic marks, including posttranslational histone modifications, DNA methylation, and populations of small noncoding RNAs, in the development of offspring stress axis sensitivity and disease risk. Copyright © 2015 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Pain-related stress in the Neonatal Intensive Care Unit and salivary cortisol reactivity to socio-emotional stress in 3-month-old very preterm infants.

Science.gov (United States)

Provenzi, Livio; Giusti, Lorenzo; Fumagalli, Monica; Tasca, Hilarj; Ciceri, Francesca; Menozzi, Giorgia; Mosca, Fabio; Morandi, Francesco; Borgatti, Renato; Montirosso, Rosario

2016-10-01

Very preterm (VPT) infants are hospitalized in the Neonatal Intensive Care Unit (NICU) and exposed to varying levels of skin-breaking procedures (pain-related stress), even in absence of severe clinical conditions. Repeated and prolonged pain exposure may alter hypothalamic-pituitary-adrenal (HPA) axis reactivity in VPT infants. During the post-discharge period, altered HPA axis reactivity has been documented in response to non-social stressors, using salivary cortisol as a biomarker. However, little is known about the effects of NICU pain-related stress on subsequent HPA axis reactivity to socio-emotional stress in infants. We examined the relationship between pain-related stress in NICU and HPA axis reactivity (i.e., salivary cortisol reactivity) to an age-appropriate socio-emotional condition in 37 healthy VPT infants compared to 53 full-term (FT) controls. The number of skin-breaking procedures was obtained across NICU stay for VPT infants. At 3 months (corrected age for prematurity), all infants participated in the maternal Face-to-Face Still-Face (FFSF) procedure, in order to assess HPA axis reactivity to socio-emotional stress (i.e., maternal unresponsiveness). VPT infants exhibited a blunted salivary cortisol reactivity, which was associated with the amount of skin-breaking procedures during NICU: greater pain-related stress predicted lower salivary cortisol reactivity, adjusting for neonatal confounders. These findings further advance our knowledge of how early exposure to pain-related stress in NICU contributes to the programming of an altered HPA axis reactivity to socio-emotional stress in 3-month-old VPT infants, even in the absence of major perinatal complications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypothalamic-pituitary-adrenal axis tonus is associated with hippocampal microstructural asymmetry

DEFF Research Database (Denmark)

Madsen, Kathrine Skak; Jernigan, Terry L; Iversen, Pernille

2012-01-01

It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since there is gr......It is well-established that prolonged high levels of cortisol have adverse effects on hippocampal neurons and glial cells. Morphometric studies linking hippocampus volume to basal HPA-axis activity, however, have yielded less consistent results. Asymmetry may also be considered, since....... Observed associations raise a number of possibilities, among them an asymmetric role of the hippocampus on HPA-axis regulation, or conversely, that individual variations in secreted cortisol, perhaps associated with stress, may have lateralized effects on hippocampal microstructure. Our results point...

HPA and SAM axis responses as correlates of self- vs parental ratings of anxiety in boys with an Autistic Disorder.

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Bitsika, Vicki; Sharpley, Christopher F; Sweeney, John A; McFarlane, James R

2014-03-29

Anxiety and Autistic Disorder (AD) are both neurological conditions and both disorders share some features that make it difficult to precisely allocate specific symptoms to each disorder. HPA and SAM axis activities have been conclusively associated with anxiety, and may provide a method of validating anxiety rating scale assessments given by parents and their children with AD about those children. Data from HPA axis (salivary cortisol) and SAM axis (salivary alpha amylase) responses were collected from a sample of 32 high-functioning boys (M age=11yr) with an Autistic Disorder (AD) and were compared with the boys' and their mothers' ratings of the boys' anxiety. There was a significant difference between the self-ratings given by the boys and ratings given about them by their mothers. Further, only the boys' self-ratings of their anxiety significantly predicted the HPA axis responses and neither were significantly related to SAM axis responses. Some boys showed cortisol responses which were similar to that previously reported in children who had suffered chronic and severe anxiety arising from stressful social interactions. As well as suggesting that some boys with an AD can provide valid self-assessments of their anxiety, these data also point to the presence of very high levels of chronic HPA-axis arousal and consequent chronic anxiety in these boys. Copyright © 2014 Elsevier Inc. All rights reserved.

On the stress-free lattice expansion of porous cordierite

International Nuclear Information System (INIS)

Bruno, Giovanni; Efremov, Alexander M.; Clausen, Bjorn; Balagurov, Anatoly M.; Simkin, Valeriy N.; Wheaton, Bryan R.; Webb, James E.; Brown, Donald W.

2010-01-01

An extensive investigation of the lattice expansion (up to 1200 deg. C) of porous synthetic cordierite (obtained by firing a mixture of talc, clay, alumina and silica) was carried out using time-of-flight neutron diffraction at LANSCE, Los Alamos, NM, USA and FNLP, Dubna, Russia. An extruded rod and several powders, with different particle size (dispersity), were studied, with the aim of monitoring the variation of the (lattice) micro-strain as a function of temperature and its influence on the microscopic and macroscopic thermal expansion. Results show a different expansion of the a- and b-axes of the orthorhombic cell (in the rod above 800 deg. C). While the finest powder seems to contract more along the c-axis, thus hinting at the presence of smaller stress, the integral peak width increases as a function of temperature in the intermediate range (300-700 deg. C). This could be explained by the integrity factor modeling in terms of micro-cracking. In polycrystalline cordierite, the model implies tension along the a- and b-axes (positive thermal expansion) accompanied by compression along the c-axis (negative thermal expansion) and a stress release upon cooling, via a thermal micro-cracking mechanism. The calculations of the cordierite macroscopic thermal expansion having as input crystal axial expansions assumed to be stress-free allowed us to conclude that even a fine powder (5 μm particle size) cannot be considered completely stress-free. This conclusion is supported by microstructural observations.

Behavioral and neuroendocrine consequences of juvenile stress combined with adult immobilization in male rats.

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Fuentes, Silvia; Carrasco, Javier; Armario, Antonio; Nadal, Roser

2014-08-01

Exposure to stress during childhood and adolescence increases vulnerability to developing several psychopathologies in adulthood and alters the activity of the hypothalamic-pituitary-adrenal (HPA) axis, the prototypical stress system. Rodent models of juvenile stress appear to support this hypothesis because juvenile stress can result in reduced activity/exploration and enhanced anxiety, although results are not always consistent. Moreover, an in-depth characterization of changes in the HPA axis is lacking. In the present study, the long-lasting effects of juvenile stress on adult behavior and HPA function were evaluated in male rats. The juvenile stress consisted of a combination of stressors (cat odor, forced swim and footshock) during postnatal days 23-28. Juvenile stress reduced the maximum amplitude of the adrenocorticotropic hormone (ACTH) levels (reduced peak at lights off), without affecting the circadian corticosterone rhythm, but other aspects of the HPA function (negative glucocorticoid feedback, responsiveness to further stressors and brain gene expression of corticotrophin-releasing hormone and corticosteroid receptors) remained unaltered. The behavioral effects of juvenile stress itself at adulthood were modest (decreased activity in the circular corridor) with no evidence of enhanced anxiety. Imposition of an acute severe stressor (immobilization on boards, IMO) did not increase anxiety in control animals, as evaluated one week later in the elevated-plus maze (EPM), but it potentiated the acoustic startle response (ASR). However, acute IMO did enhance anxiety in the EPM, in juvenile stressed rats, thereby suggesting that juvenile stress sensitizes rats to the effects of additional stressors. Copyright © 2014 Elsevier Inc. All rights reserved.

Stress effects on mood, HPA axis, and autonomic response: comparison of three psychosocial stress paradigms.

Directory of Open Access Journals (Sweden)

Grace E Giles

Full Text Available Extensive experimental psychology research has attempted to parse the complex relationship between psychosocial stress, mood, cognitive performance, and physiological changes. To do so, it is necessary to have effective, validated methods to experimentally induce psychosocial stress. The Trier Social Stress Test (TSST is the most commonly used method of experimentally inducing psychosocial stress, but it is resource intensive. Less resource intense psychosocial stress tasks include the Socially Evaluative Cold Pressor Task (SECPT and a computerized mental arithmetic task (MAT. These tasks effectively produce a physiological and psychological stress response and have the benefits of requiring fewer experimenters and affording data collection from multiple participants simultaneously. The objective of this study was to compare the magnitude and duration of these three experimental psychosocial stress induction paradigms. On each of four separate days, participants completed either a control non-stressful task or one of the three experimental stressors: the TSST, SECPT, or MAT. We measured mood, working memory performance, salivary cortisol and alpha-amylase (AA, and heart rate. The TSST and SECPT exerted the most robust effects on mood and physiological measures. TSST effects were generally evident immediately post-stress as well as 10- and 20-minutes after stress cessation, whereas SECPT effects were generally limited to the duration of the stressor. The stress duration is a key determinant when planning a study that utilizes an experimental stressor, as researchers may be interested in collecting dependent measures prior to stress cessation. In this way, the TSST would allow the investigator a longer window to administer tasks of interest.

Interplay Between the Gut-Brain Axis, Obesity and Cognitive Function

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Agustí, Ana; García-Pardo, Maria P.; López-Almela, Inmaculada; Campillo, Isabel; Maes, Michael; Romaní-Pérez, Marina; Sanz, Yolanda

2018-01-01

Obesity continues to be one of the major public health problems due to its high prevalence and co-morbidities. Common co-morbidities not only include cardiometabolic disorders but also mood and cognitive disorders. Obese subjects often show deficits in memory, learning and executive functions compared to normal weight subjects. Epidemiological studies also indicate that obesity is associated with a higher risk of developing depression and anxiety, and vice versa. These associations between pathologies that presumably have different etiologies suggest shared pathological mechanisms. Gut microbiota is a mediating factor between the environmental pressures (e.g., diet, lifestyle) and host physiology, and its alteration could partly explain the cross-link between those pathologies. Westernized dietary patterns are known to be a major cause of the obesity epidemic, which also promotes a dysbiotic drift in the gut microbiota; this, in turn, seems to contribute to obesity-related complications. Experimental studies in animal models and, to a lesser extent, in humans suggest that the obesity-associated microbiota may contribute to the endocrine, neurochemical and inflammatory alterations underlying obesity and its comorbidities. These include dysregulation of the HPA-axis with overproduction of glucocorticoids, alterations in levels of neuroactive metabolites (e.g., neurotransmitters, short-chain fatty acids) and activation of a pro-inflammatory milieu that can cause neuro-inflammation. This review updates current knowledge about the role and mode of action of the gut microbiota in the cross-link between energy metabolism, mood and cognitive function. PMID:29615850

Mediterranean coastal dune vegetation: Are disturbance and stress the key selective forces that drive the psammophilous succession?

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Ciccarelli, Daniela

2015-11-01

Plant communities of coastal dunes are distributed along a characteristic sea-inland gradient. Generally, there is a shift from annual and short height species with small leaves in the initial successional stages to perennial tall shrubs with tough leaves in later phases. Assessing the community-weighted mean (CWM) trait values is used in plant ecology to describe ecosystem properties especially during succession. In particular, CSR (Competitive, Stress-tolerant, and Ruderal strategy) classification allows us to explore community functional shifts in terms of disturbance, stress and competition selective forces. The functional basis of the psammophilous succession was studied based on the following questions: (1) Can we circumscribe different functional types among plant species of Mediterranean coastal dunes? (2) How do CWM trait values vary along the environmental sea-inland gradient? (3) What is the relative importance of competition, stress and disturbance in the processes of plant community assembling? (4) Can we postulate that along primary successions there is generally a shift from ruderality to stress-tolerance? An explorative analysis of functional groups was performed by Non-Metric Multidimensional Scaling (NMDS) analysing nine morpho-functional traits measured for 45 taxa from 880 dune plots localised in Tuscany (central Italy, Europe). NMDS ordination showed a scattered distribution of psammophytes that could not be delimited in precise plant functional types. The first NMDS axis has been interpreted as a leaf economics axis because it was correlated to leaf area (LA) and leaf dry matter content (LDMC), while the second one was a plant size axis because of its correlation with canopy height. Along the sea-inland gradient, pioneer plant communities of upper beach were dominated by ruderals (with the lowest values of LDMC and specific leaf area - SLA), well-adapted to the harsh environmental conditions of coastal dunes. More distant from the sea, where

Thermal and mechanical stresses in a functionally graded thick sphere

International Nuclear Information System (INIS)

Eslami, M.R.; Babaei, M.H.; Poultangari, R.

2005-01-01

In this paper, a general solution for the one-dimensional steady-state thermal and mechanical stresses in a hollow thick sphere made of functionally graded material is presented. The temperature distribution is assumed to be a function of radius, with general thermal and mechanical boundary conditions on the inside and outside surfaces of the sphere. The material properties, except Poisson's ratio, are assumed to vary along the radius r according to a power law function. The analytical solution of the heat conduction equation and the Navier equation lead to the temperature profile, radial displacement, radial stress, and hoop stress as a function of radial direction

Characterization of the Hypothalamic-Pituitary-Adrenal-Axis in Familial Longevity under Resting Conditions

DEFF Research Database (Denmark)

Jansen, Steffy W; Roelfsema, Ferdinand; Akintola, Abimbola A

2015-01-01

OBJECTIVE: The hypothalamic-pituitary-adrenal (HPA)-axis is the most important neuro-endocrine stress response system of our body which is of critical importance for survival. Disturbances in HPA-axis activity have been associated with adverse metabolic and cognitive changes. Humans enriched...... for longevity have less metabolic and cognitive disturbances and therefore diminished activity of the HPA axis may be a potential candidate mechanism underlying healthy familial longevity. Here, we compared 24-h plasma ACTH and serum cortisol concentration profiles and different aspects of the regulation...... of the HPA-axis in offspring from long-lived siblings, who are enriched for familial longevity and age-matched controls. DESIGN: Case-control study within the Leiden Longevity study cohort consisting of 20 middle-aged offspring of nonagenarian siblings (offspring) together with 18 partners (controls...

Hypothalamic-pituitary-adrenal axis activity is not elevated in a songbird (Junco hyemalis) preparing for migration.

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Bauer, Carolyn M; Needham, Katie B; Le, Chuong N; Stewart, Emily C; Graham, Jessica L; Ketterson, Ellen D; Greives, Timothy J

2016-06-01

During spring, increasing daylengths stimulate gonadal development in migratory birds. However, late-stage reproductive development is typically postponed until migration has been completed. The hypothalamic-pituitary-adrenal (HPA) axis regulates the secretion of glucocorticoids, which have been associated with pre-migratory hyperphagia and fattening. The HPA-axis is also known to suppress the hypothalamic-pituitary-gonadal (HPG) axis, suggesting the possibility that final transition into the breeding life history stage may be slowed by glucocorticoids. We hypothesized that greater HPA-axis activity in individuals preparing for migration may foster preparation for migration while simultaneously acting as a "brake" on the development of the HPG-axis. To test this hypothesis, we sampled baseline corticosterone (CORT), stress-induced CORT, and negative feedback efficacy of Dark-eyed Juncos (Junco hyemalis) in an overwintering population that included both migratory (J.h. hyemalis) and resident (J.h. carolinensis) individuals. We predicted that compared to residents, migrants would have higher baseline CORT, higher stress-induced CORT, and weaker negative feedback. Juncos were sampled in western Virginia in early March, which was about 2-4wk before migratory departure for migrants and 4-5wk before first clutch initiation for residents. Contrary to our predictions, we found that migrants had lower baseline and stress-induced CORT and similar negative feedback efficacy compared with residents, which suggests that delayed breeding in migrants is influenced by other physiological mechanisms. Our findings also suggest that baseline CORT is not elevated during pre-migratory fattening, as migrants had lower baseline CORT and were fatter than residents. Copyright © 2015 Elsevier Inc. All rights reserved.

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.

Mastication as a Stress-Coping Behavior

Directory of Open Access Journals (Sweden)

Kin-ya Kubo

2015-01-01

Full Text Available Exposure to chronic stress induces various physical and mental effects that may ultimately lead to disease. Stress-related disease has become a global health problem. Mastication (chewing is an effective behavior for coping with stress, likely due to the alterations chewing causes in the activity of the hypothalamic-pituitary-adrenal axis and autonomic nervous system. Mastication under stressful conditions attenuates stress-induced increases in plasma corticosterone and catecholamines, as well as the expression of stress-related substances, such as neurotrophic factors and nitric oxide. Further, chewing reduces stress-induced changes in central nervous system morphology, especially in the hippocampus and hypothalamus. In rodents, chewing or biting on wooden sticks during exposure to various stressors reduces stress-induced gastric ulcer formation and attenuates spatial cognitive dysfunction, anxiety-like behavior, and bone loss. In humans, some studies demonstrate that chewing gum during exposure to stress decreases plasma and salivary cortisol levels and reduces mental stress, although other studies report no such effect. Here, we discuss the neuronal mechanisms that underline the interactions between masticatory function and stress-coping behaviors in animals and humans.

[Immune dysfunction and cognitive deficit in stress and physiological aging. Part II: New approaches to cognitive disorder prevention and treatment ].

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Pukhal'skiĭ, A L; Shmarina, G V; Aleshkin, V A

2014-01-01

Long-term stress as well as physiological aging result in similar immunological and hormonal disturbances including hypothalamic-pituitary-adrenal) axis depletion, aberrant immune response (regulatory T-cells, Tregs, and T(h17)-lymphocyte accumulation) and decreased dehydroepian-drosterone synthesis both in the brain and in the adrenal glands. Since the main mechanisms of inflammation control, "prompt" (stress hormones) and "delayed" (Tregs), are broken, serum cytokine levels increase and become sufficient for blood-brain-barrier disruption. As a result peripheral cytokines penetrate into the brain where they begin to perform new functions. Structural and functional alterations of blood-brain-barrier as well as stress- (or age-) induced neuroinflammation promote influx of bone marrow derived dendritic cells and lymphocyte effectors into the brain parenchyma. Thereafter, mass intrusion ofpro-inflammatory mediators and immune cells having a lot of specific targets alters the brain work that we can observe both in humans and in animal experiments. The concept of stressful cognitive dysfunction, which is under consideration in this review, allows picking out several therapeutic targets: 1) reduction of excessive Treg accumulation; 2) supporting hypothalamic-pituitary-adrenal axis and inflammatory reaction attenuation; 3) recovery of dehydroepiandrosterone level; 4) improvement of blood-brain-barrier function.

Interface between hypothalamic-pituitary-adrenal axis and brain-derived neurotrophic factor in depression.

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Kunugi, Hiroshi; Hori, Hiroaki; Adachi, Naoki; Numakawa, Tadahiro

2010-10-01

Although the pathophysiology of depressive disorder remains elusive, two hypothetical frameworks seem to be promising: the involvement of hypothalamic pituitary-adrenal (HPA) axis abnormalities and brain-derived neurotrophic factor (BDNF) in the pathogenesis and in the mechanism of action of antidepressant treatments. In this review, we focused on research based on these two frameworks in relation to depression and related conditions and tried to formulate an integrated theory of the disorder. Hormonal challenge tests, such as the dexamethasone/corticotropin-releasing hormone test, have revealed elevated HPA activity (hypercortisolism) in at least a portion of patients with depression, although growing evidence has suggested that abnormally low HPA axis (hypocortisolism) has also been implicated in a variety of stress-related conditions. Several lines of evidence from postmortem studies, animal studies, blood levels, and genetic studies have suggested that BDNF is involved in the pathogenesis of depression and in the mechanism of action of biological treatments for depression. Considerable evidence has suggested that stress reduces the expression of BDNF and that antidepressant treatments increase it. Moreover, the glucocorticoid receptor interacts with the specific receptor of BDNF, TrkB, and excessive glucocorticoid interferes with BDNF signaling. Altered BDNF function is involved in the structural changes and possibly impaired neurogenesis in the brain of depressed patients. Based on these findings, an integrated schema of the pathological and recovery processes of depression is illustrated. © 2010 The Authors. Psychiatry and Clinical Neurosciences © 2010 Japanese Society of Psychiatry and Neurology.

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.

Progressive dysregulation of autonomic and HPA axis functions in HIV-1 clade C infection in South India.

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Chittiprol, Seetharamaiah; Kumar, Adarsh M; Satishchandra, P; Taranath Shetty, K; Bhimasena Rao, R S; Subbakrishna, D K; Philip, Mariyamma; Satish, K S; Ravi Kumar, H; Kumar, Mahendra

2008-01-01

Human immunodeficiency virus type 1 (HIV-1) infection causes a wide spectrum of abnormalities in neurological, neuropsychological, and neuroendocrinological functions. Several studies report disturbance in autonomic nervous system (ANS) and hypothalamic pituitary-adrenal (HPA) axis function in HIV-1B infected individuals. However, no such investigations on the effect of HIV-1 clade C infection, particularly during the initial phase of the disease progression, have been reported. The present investigations were carried out longitudinally over a 2-year period at 12 monthly intervals in clinically asymptomatic HIV-1 clade C seropositive patients (n=120) and seronegative control subjects (n=29). We determined both the basal levels and the dynamic changes in plasma levels of norepinephrine (NE), epinephrine (E), adrenocorticotrophic hormone (ACTH) and cortisol (CORT). Studies were also extended longitudinally (at three separate yearly visits of each participant), to evaluate the response of autonomic and HPA axis to mirror star tracing challenge test (MSTCT) and the values were determined as area under the curve (AUC, corrected for baseline levels of NE, E, ACTH, and CORT). The findings show that the values of basal plasma NE levels, as well as NE response to MSTCT (AUC) at the first visit of HIV-1 seropositive individuals did not differ from those found in the control subjects (NE, pg/ml, HIV-1C=313.5+/-12.7 vs. controls=353.0+/-21.3; p=NS; AUC, HIV-1C=225+/-14.75 vs. controls=232.7+/-19.34; p=NS, respectively). At the subsequent two visits of HIV-1 positive patients however, NE response to MSTCT challenge was progressively attenuated (AUC=235+/-19.5 and 162.7+/-13.6; p<0.01 and 0.05, respectively) compared to that found at the first visit. On the other hand, plasma levels of E as well as E response to MSTCT at the first visit were significantly lower in HIV-1C seropositive individuals compared to those in the control subjects (pg/ml, HIV-1C=77.30+/-5.7 vs. controls

Morphological changes in the pituitary-adrenocortical axis in natives of La Paz

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Gosney, John; Heath, Donald; Williams, David; Rios-Dalenz, Jaime

1991-03-01

Increased activity of the hypothalamic-pituitary-adrenocortical axis is part of the response to the stress of initial exposure to hypoxia, but there is evidence to suggest that it persists after homeostatic stability has been regained and acclimatization achieved. The adrenal glands of five lifelong residents of La Paz, Bolivia, who had lived at altitudes in the range 3600 3800 m, were significantly larger than those in age-matched controls from sea level (15.3g vs 10.4g; Ppituitary glands of the highlanders were not significantly different in size from those of the controls (0.67 g vs 0.51 g), but contained larger populations of corticotrophs expressed in terms of the total cell population of their anterior lobes (25.6% vs 19.4%; P<0.001). In conjunction with other studies of this endocrine axis in man and animals exposed to a hypoxic environment, these data suggest that greater amounts of adrenocorticotrophic hormone (ACTH) are required to maintain normal adrenocortical function under such circumstances, probably as a result of hypoxic inhibition of adrenocortical sensitivity to stimulation. Physiological hyperplasia of the adrenal cortex may be common in people living at high altitude.

Salubrious effects of oxytocin on social stress-induced deficits

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Smith, Adam S.; Wang, Zuoxin

2012-01-01

Social relationships are a fundamental aspect of life, affecting social, psychological, physiological, and behavioral functions. While social interactions can attenuate stress and promote health, disruption, confrontations, isolation, or neglect in the social environment can each be major stressors. Social stress can impair the basal function and stress-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis, impairing function of multiple biological systems and posing a risk to mental and physical health. In contrast, social support can ameliorate stress-induced physiological and immunological deficits, reducing the risk of subsequent psychological distress and improving an individual's overall well-being. For better clinical treatment of these physiological and mental pathologies, it is necessary to understand the regulatory mechanisms of stress-induced pathologies as well as determine the underlying biological mechanisms that regulate social buffering of the stress system. A number of ethologically relevant animal models of social stress and species that form strong adult social bonds have been utilized to study the etiology, treatment, and prevention of stress-related disorders. While undoubtedly a number of biological pathways contribute to the social buffering of the stress response, the convergence of evidence denotes the regulatory effects of oxytocin in facilitating social bond-promoting behaviors and their effect on the stress response. Thus, oxytocin may be perceived as a common regulatory element of the social environment, stress response, and stress-induced risks on mental and physical health. PMID:22178036

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.

Active optics: off axis aspherics generation for high contrast imaging

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Hugot, E.; Laslandes, M.; Ferrari, M.; Vives, S.; Moindrot, S.; El Hadi, K.; Dohlen, K.

2017-11-01

Active Optics methods, based on elasticity theory, allow the aspherisation of optical surfaces by stress polishing but also active aspherisation in situ. Researches in this field will impact the final performance and the final cost of any telescope or instrument. The stress polishing method is well suited for the superpolishing of aspheric components for astronomy. Its principle relies on spherical polishing with a full-sized tool of a warped substrate, which becomes aspherical once unwarped. The main advantage of this technique is the very high optical quality obtained either on form or on high spatial frequency errors. Furthermore, the roughness can be decreased down to a few angstroms, thanks the classical polishing with a large pitch tool, providing a substantial gain on the final scientific performance, for instance on the contrast on coronagraphic images, but also on the polishing time and cost. Stress polishing is based on elasticity theory, and requires an optimised deformation system able to provide the right aspherical form on the optical surface during polishing. The optical quality of the deformation is validated using extensive Finite Element Analysis, allowing an estimation of residuals and an optimisation of the warping harness. We describe here the work realised on stress polishing of toric mirrors for VLT-SPHERE and then our actual work on off axis aspherics (OAA) for the ASPIICS-Proba3 mission for solar coronagraphy. The ASPIICS optical design made by Vives et al is a three mirrors anastigmat including a concave off axis hyperboloid and a convex off axis parabola (OAP). We are developing a prototype in order to demonstrate the feasibility of this type of surface, using a multi-mode warping harness (Lemaitre et al). Furthermore, we present our work on variable OAP, meaning the possibility to adjust the shape of a simple OAP in situ with a minimal number of actuators, typically one actuator per optical mode (Focus, Coma and Astigmatism

A randomized trial on mineralocorticoid receptor blockade in men: effects on stress responses, selective attention, and memory.

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Cornelisse, Sandra; Joëls, Marian; Smeets, Tom

2011-12-01

Corticosteroids, released in high amounts after stress, exert their effects via two different receptors in the brain: glucocorticoid receptors (GRs) and mineralocorticoid receptors (MRs). GRs have a role in normalizing stress-induced effects and promoting consolidation, while MRs are thought to be important in determining the threshold for activation of the hypothalamic-pituitary-adrenal (HPA) axis. We investigated the effects of MR blockade on HPA axis responses to stress and stress-induced changes in cognitive function. In a double-blind, placebo-controlled study, 64 healthy young men received 400 mg of the MR antagonist spironolactone or placebo. After 1.5 h, they were exposed to either a Trier Social Stress Test or a non-stressful control task. Responses to stress were evaluated by hormonal, subjective, and physiological measurements. Afterwards, selective attention, working memory, and long-term memory performance were assessed. Spironolactone increased basal salivary cortisol levels as well as cortisol levels in response to stress. Furthermore, spironolactone significantly impaired selective attention, but only in the control group. The stress group receiving spironolactone showed impaired working memory performance. By contrast, long-term memory was enhanced in this group. These data support a role of MRs in the regulation of the HPA axis under basal conditions as well as in response to stress. The increased availability of cortisol after spironolactone treatment implies enhanced GR activation, which, in combination with MR blockade, presumably resulted in a decreased MR/GR activation ratio. This condition influences both selective attention and performance in various memory tasks.

HPA axis reactivity to pharmacologic and psychological stressors in euthymic women with histories of postpartum versus major depression.

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Ferguson, Elizabeth H; Di Florio, Arianna; Pearson, Brenda; Putnam, Karen T; Girdler, Susan; Rubinow, David R; Meltzer-Brody, Samantha

2017-06-01

It is unclear whether women with a history of postpartum depression (PPD) have residual, abnormal hypothalamic-pituitary-adrenal (HPA) axis reactivity, as has been reported in major depression (MDD). Further unclear is whether the abnormalities in HPA axis reactivity associated with MDD represent a stable, underlying predisposition or a state-dependent phenomenon. This study sought the following: (1) to determine if euthymic postpartum women with a history of depression have an abnormal HPA axis reactivity to pharmacologic and psychological challenges and (2) to compare HPA reactivity in women with histories of PPD versus MDD. As a secondary objective, we wanted to determine the influence of trauma history on HPA axis function. Forty-five parous (12-24 months postpartum), euthymic women with history of MDD (n = 15), PPD (n = 15), and controls (n = 15) completed pharmacologic (dexamethasone/corticotropin-releasing hormone (CRH) test [DEX/CRH]) and psychological (Trier social stress test [TSST]) challenges during the luteal phase. Outcome measures were cortisol and adrenocorticotropic hormone (ACTH) response after DEX/CRH, and blood pressure, heart rate, epinephrine, norepinephrine, and cortisol response during the TSST. All groups had robust cortisol and ACTH response to DEX/CRH and cortisol response to TSST. Groups did not differ significantly in cortisol or ACTH response to DEX/CRH or in blood pressure, heart rate, epinephrine, norepinephrine, or cortisol response to TSST. Cortisol/ACTH ratio did not differ significantly between groups. Trauma history was associated with decreased cortisol response to DEX/CRH in women with histories of MDD, which was not significant after correction (F 8,125 , p = 0.02, Greenhouse-Geisser corrected p = 0.11). Currently euthymic women with histories of MDD or PPD did not demonstrate residual abnormal stress responsivity following administration of either a pharmacologic or psychological stressor.

Stressful Life Events in Children With Functional Defecation Disorders.

Science.gov (United States)

Philips, Elise M; Peeters, Babette; Teeuw, Arianne H; Leenders, Arnold G E; Boluyt, Nicole; Brilleslijper-Kater, Sonja N; Benninga, Marc A

2015-10-01

The aim of the study was to determine the prevalence of stressful life events including (sexual) abuse in children with functional defecation disorders by performing a systematic review. We searched MEDLINE, EMBASE, and PsycINFO for cohort, case-control and cross-sectional studies investigating the prevalence of stressful life events, including (sexual) abuse in children with functional defecation disorders. The search yielded 946 articles, of which 8 were included with data from 654 children with functional constipation and 1931 children with (constipation-associated) fecal incontinence (FI). Overall, children with functional defecation disorders had been significantly more exposed to stressful life events than healthy children, with prevalence rates ranging from 1.6% to 90.9%. Being bullied, being a relational victim, interruption of toilet training, punishment by parents during toilet training, and hospitalization were significantly related to FI, whereas separation from the best friend, failure in an examination, severe illness in a close family member, loss of job by a parent, frequent punishment, and living in a war-affected area were significantly related to constipation. Only 1 study measured the prevalence of child abuse, which reported a significantly higher prevalence of child (sexual) abuse in children with FI compared with controls. The prevalence of stressful life events, including (sexual) abuse is significantly higher in children with functional defecation disorders compared with healthy children. To gain more insight into the true prevalence of child (sexual) abuse in children with functional defecation disorders, more studies are clearly needed.

Dietary Manipulations That Induce Ketosis Activate the HPA Axis in Male Rats and Mice: A Potential Role for Fibroblast Growth Factor-21.

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Ryan, Karen K; Packard, Amy E B; Larson, Karlton R; Stout, Jayna; Fourman, Sarah M; Thompson, Abigail M K; Ludwick, Kristen; Habegger, Kirk M; Stemmer, Kerstin; Itoh, Nobuyuki; Perez-Tilve, Diego; Tschöp, Matthias H; Seeley, Randy J; Ulrich-Lai, Yvonne M

2018-01-01

In response to an acute threat to homeostasis or well-being, the hypothalamic-pituitary-adrenocortical (HPA) axis is engaged. A major outcome of this HPA axis activation is the mobilization of stored energy, to fuel an appropriate behavioral and/or physiological response to the perceived threat. Importantly, the extent of HPA axis activity is thought to be modulated by an individual's nutritional environment. In this study, we report that nutritional manipulations signaling a relative depletion of dietary carbohydrates, thereby inducing nutritional ketosis, acutely and chronically activate the HPA axis. Male rats and mice maintained on a low-carbohydrate high-fat ketogenic diet (KD) exhibited canonical markers of chronic stress, including increased basal and stress-evoked plasma corticosterone, increased adrenal sensitivity to adrenocorticotropin hormone, increased stress-evoked c-Fos immunolabeling in the paraventricular nucleus of the hypothalamus, and thymic atrophy, an indicator of chronic glucocorticoid exposure. Moreover, acutely feeding medium-chain triglycerides (MCTs) to rapidly induce ketosis among chow-fed male rats and mice also acutely increased HPA axis activity. Lastly, and consistent with a growing literature that characterizes the hepatokine fibroblast growth factor-21 (FGF21) as both a marker of the ketotic state and as a key metabolic stress hormone, the HPA response to both KD and MCTs was significantly blunted among mice lacking FGF21. We conclude that dietary manipulations that induce ketosis lead to increased HPA axis tone, and that the hepatokine FGF21 may play an important role to facilitate this effect. Copyright © 2018 Endocrine Society.

Mothers' parenting stress is associated with salivary cortisol profiles in children with attention deficit hyperactivity disorder.

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Korpa, Terpsichori; Pervanidou, Panagiota; Angeli, Eleni; Apostolakou, Filia; Papanikolaou, Katerina; Papassotiriou, Ioannis; Chrousos, George P; Kolaitis, Gerasimos

2017-03-01

The aim of this study was to explore the relation between mothers' parenting stress and the functioning of the hypothalamic-pituitary-adrenal axis (HPAA), as expressed by daily salivary cortisol concentrations, in their children diagnosed with attention deficit hyperactivity disorder (ADHD). Seventy-five children aged 6-11 years diagnosed with ADHD predominant hyperactive-impulsive/combined (ADHD-HI/C, N = 49) and inattentive symptoms (ADHD-I, N = 26) and 45 healthy peers and their mothers participated in the study. Μothers completed measures assessing their children's ADHD status, perceived parenting stress (Parenting Stress Index - Short Form, PSI-SF), mothers' symptoms of psychopathology, social support and socioeconomic status. Children's salivary cortisol samples were collected at six different time points on a single day. Mothers of children with ADHD-HI/C reported higher levels of parenting stress than mothers of children with ADHD-I and controls. All PSI-SF subscales showed significant associations with children's cortisol awakening response (CAR) in both ADHD groups, with the exception of the parental distress subscale in the ADHD-I group. In both ADHD groups, the parent-child dysfunctional interaction subscale, the difficult child subscale and the PSI total score were significantly associated with children's CAR. An interrelation is revealed between mothers' high levels of parenting stress and HPAA functioning in children with ADHD. In this population, CAR has been identified as a sensitive peripheral measure of HPAA functioning in children. Lay summaryThis study showed that in families of children diagnosed with ADHD, there is a complex relation between the mothers' high levels of parenting stress and children's atypical hypothalamic-pituitary-adrenal axis functioning.

Prevalence and Axis I Comorbidity of Full and Partial Posttraumatic Stress Disorder in the United States: Results from Wave 2 of the National Epidemiologic Survey on Alcohol and Related Conditions

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Pietrzak, Robert H.; Goldstein, Risë B.; Southwick, Steven M.; Grant, Bridget F.

2010-01-01

The present study used data from the Wave 2 National Epidemiologic Survey on Alcohol and Related Conditions (n=34,653) to examine lifetime Axis I psychiatric comorbidity of posttraumatic stress disorder (PTSD) in a nationally representative sample of U.S. adults. Lifetime prevalences±standard errors of PTSD and partial PTSD were 6.4%±0.18 and 6.6%±0.18, respectively. Rates of PTSD and partial PTSD were higher among women (8.6%±0.26 and 8.6%±0.26) than men (4.1%±0.19 and 4.5%±0.21). Respondents with both PTSD and partial PTSD most commonly reported unexpected death of someone close, serious illness or injury to someone close, and sexual assault as their worst stressful experiences. PTSD and partial PTSD were associated with elevated lifetime rates of mood, anxiety, and substance use disorders, and suicide attempts. Respondents with partial PTSD generally had intermediate odds of comorbid Axis I disorders and psychosocial impairment relative to trauma controls and full PTSD. PMID:21168991

Impact of prenatal stress on offspring glucocorticoid levels: A phylogenetic meta-analysis across 14 vertebrate species.

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Thayer, Zaneta M; Wilson, Meredith A; Kim, Andrew W; Jaeggi, Adrian V

2018-03-21

Prenatal exposure to maternal stress is commonly associated with variation in Hypothalamic Pituitary Adrenal (HPA)-axis functioning in offspring. However, the strength or consistency of this response has never been empirically evaluated across vertebrate species. Here we meta-analyzed 114 results from 39 studies across 14 vertebrate species using Bayesian phylogenetic mixed-effects models. We found a positive overall effect of prenatal stress on offspring glucocorticoids (d' = 0.43) though the 95% Highest Posterior Density Interval overlapped with 0 (-0.16-0.95). Meta-regressions of potential moderators highlighted that phylogeny and life history variables predicted relatively little variation in effect size. Experimental studies (d' = 0.64) produced stronger effects than observational ones (d' = -0.01), while prenatal stress affected glucocorticoid recovery following offspring stress exposure more strongly (d' = 0.75) than baseline levels (d' = 0.48) or glucocorticoid peak response (d' = 0.36). These findings are consistent with the argument that HPA-axis sensitivity to prenatal stress is evolutionarily ancient and occurs regardless of a species' overall life history strategy. These effects may therefore be especially important for mediating intra-specific life-history variation. In addition, these findings suggest that animal models of prenatal HPA-axis programming may be appropriate for studying similar effects in humans.

A novel hybrid stress-function finite element method immune to severe mesh distortion

International Nuclear Information System (INIS)

Cen Song; Zhou Mingjue; Fu Xiangrong

2010-01-01

This paper introduces a hybrid stress-function finite element method proposed recently for developing 2D finite element models immune to element shapes. Deferent from the first version of the hybrid-stress element constructed by Pian, the stress function φ of 2D elastic or fracture problem is regarded as the functional variable of the complementary energy functional. Then, the basic analytical solutions of φ are taken as the trial functions for finite element models, and meanwhile, the corresponding unknown stress-function constants are introduced. By using the principle of minimum complementary energy, these unknown stress-function constants can be expressed in terms of the displacements along element edges. Finally, the complementary energy functional can be rewritten in terms of element nodal displacement vector, and thus, the element stiffness matrix of such hybrid-function element can be obtained. As examples, two (8- and 12-node) quadrilateral plane elements and an arbitrary polygonal crack element are constructed by employing different basic analytical solutions of different stress functions. Numerical results show that, the 8- and 12-node plane models can produce the exact solutions for pure bending and linear bending problems, respectively, even the element shape degenerates into triangle and concave quadrangle; and the crack element can also predict accurate results with very low computational cost in analysis of stress-singularity problems.

Depressed suicide attempters with posttraumatic stress disorder.

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Ramberg, Maria; Stanley, Barbara; Ystgaard, Mette; Mehlum, Lars

2015-01-01

Posttraumatic stress disorder and major depressive disorder are well-established risk factors for suicidal behavior. This study compared depressed suicide attempters with and without comorbid posttraumatic stress disorder with respect to additional diagnoses, global functioning, depressive symptoms, substance abuse, history of traumatic exposure, and suicidal behavior. Adult patients consecutively admitted to a general hospital after a suicide attempt were interviewed and assessed for DSM-IV diagnosis and clinical correlates. Sixty-four patients (71%) were diagnosed with depression; of them, 21 patients (32%) had posttraumatic stress disorder. There were no group differences in social adjustment, depressive symptoms, or suicidal intent. However, the group with comorbid depression and posttraumatic stress disorder had more additional Axis I diagnoses, a higher degree of childhood trauma exposure, and more often reported previous suicide attempts, non-suicidal self-harm, and vengeful suicidal motives. These findings underline the clinical importance of diagnosis and treatment of posttraumatic stress disorder in suicide attempters.

Interaction of basal forebrain cholinergic neurons with the glucocorticoid system in stress regulation and cognitive impairment

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Saswati ePaul

2015-04-01

Full Text Available A substantial number of studies on basal forebrain cholinergic neurons (BFCN have provided compelling evidence for their role in the etiology of stress, cognitive aging, Alzheimer’s disease (AD, and other neurodegenerative diseases. BFCN project to a broad range of cortical sites and limbic structures, including the hippocampus, and are involved in stress and cognition. In particular, the hippocampus, the primary target tissue of the glucocorticoid stress hormones, is associated with cognitive function in tandem with hypothalamic-pituitary-adrenal (HPA axis modulation. The present review summarizes glucocorticoid and HPA axis research to date in an effort to establish the manner in which stress affects the release of acetylcholine, glucocorticoids, and their receptor in the context of cognitive processes. We attempt to provide the molecular interactive link between the glucocorticoids and cholinergic system that contributes to BFCN degeneration in stress-induced acceleration of cognitive decline in aging and AD. We also discuss the importance of animal models in facilitating such studies for pharmacological use, which could help decipher disease states and propose leads for pharmacological intervention.

Prenatal exposure to noise stress: anxiety, impaired spatial memory, and deteriorated hippocampal plasticity in postnatal life.

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Barzegar, Marzieh; Sajjadi, Fatemeh Sadat; Talaei, Sayyed Alireza; Hamidi, Gholamali; Salami, Mahmoud

2015-02-01

Sound pollution is known as an annoying phenomenon in modern life. Especially, development of organisms during fetal life is more sensitive to environmental tensions. To address a link between the behavioral and electrophysiological aspects of brain function with action of hypothalamus-pituitary-adrenal (HPA) axis in stressed animals, this study was carried out on the male Wistar rats prenatally exposed to sound stress. Groups of pregnant rats were exposed to noise stress for 1, 2, and 4 hour(s). The degree of anxiety and the spatial memory were evaluated by elevated plus maze and Morris water maze, respectively. Basic synaptic activity and long-term potentiation (LTP) induction were assessed in the CA3-CA1 pathway of hippocampus. The serum level of corticosterone was measured in the pregnant mothers and the offspring. The behavioral experiments appeared that the stressed animals performed considerably weaker than the control rats. The prenatal stress negatively affected the basic synaptic responses and led to a lower level of LTP. The pregnant animals showed an increased serum corticosterone in comparison with the nonpregnant females. Also the offspring exposed to the noise stress had a more elevated level of corticosterone than the control rats. Our findings indicate that the corticosterone concentration changes markedly coincides the results of behavioral and electrophysiological experiments. We conclude that, similar to other environmental stresses, the sound stress during fetal life efficiently disturbs both cognitive abilities and synaptic activities. The changes in action of HPA axis may contribute to problems of the brain function in the prenatally stress exposed animals. © 2014 Wiley Periodicals, Inc.

Psychological stress-relieving effects of chewing - Relationship between masticatory function-related factors and stress-relieving effects.

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Tasaka, Akinori; Kikuchi, Manaki; Nakanishi, Kousuke; Ueda, Takayuki; Yamashita, Shuichiro; Sakurai, Kaoru

2018-01-01

The objective of the present study was to investigate the relationship between masticatory function-related factors (masticatory performance, occlusal contact area, maximum bite force, number of chewing strokes, and muscle activity) and the stress-relieving effects of chewing. A total of 28 healthy male subjects were instructed to rest or chew for 10min after 30min of stress loading with arithmetic calculations. Their stress state was assessed by measuring salivary cortisol levels. Saliva was collected at three time points: before stress loading, immediately after stress loading, and 10min after stress loading. Compared to resting, chewing produced a significantly greater reduction in the rate of change in salivary cortisol levels 10min after stress loading. A negative correlation was observed between the rate of decrease in salivary cortisol levels and the number of chewing strokes. No significant correlation was observed between the rate of decrease in salivary cortisol levels and other measurement items. In healthy dentulous people, the number of chewing strokes has been shown to be a masticatory function-related factor that affects stress relief from chewing, suggesting the possibility that more appropriate chewing would produce a greater effect psychological stress relief. Copyright © 2017 Japan Prosthodontic Society. Published by Elsevier Ltd. All rights reserved.

Cognition and HPA axis reactivity in mildly to moderately depressed outpatients

DEFF Research Database (Denmark)

Krogh, Jesper; Videbech, Poul; Renvillard, Signe Groth

2012-01-01

Background: Patients with depression display neurobiological changes of the hypothalamic-pituitary axis as well as cognitive disturbances. Aims: To assess any association between hypothalamus-pituitary-adrenal (HPA) axis reactivity and memory-related cognitive functions. Methods: Depressed...... the following day at the same times. Results: Patients and controls did not differ on any memory-related cognitive skills. After dexamethasone the cortisol level was 1.7 nmol/l higher (95% CI 0.0-2.8, P =¿0.05) in depressed patients compared with controls. In the control group, but not in the patients...... after dexamethasone and visuo-spatial memory primarily driven by the healthy controls. Otherwise, no association were found between HPA axis reactivity and memory-related cognitive function....

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

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Xu, D. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Ping, J. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China); Qin, J. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Zhang, C. [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Chen, L.B. [Department of Orthopedic Surgery, Zhongnan Hospital of Wuhan University, Wuhan 430071 (China); Magdalou, J. [UMR 7561 CNRS-Nancy Université, Faculté de Médicine, Vandoeuvre-lès-Nancy (France); Wang, H., E-mail: wanghui19@whu.edu.cn [Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan 430071 (China); Research Center of Food and Drug Evaluation, Wuhan University, Wuhan 430071 (China)

2012-11-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

A hypothalamic–pituitary–adrenal axis-associated neuroendocrine metabolic programmed alteration in offspring rats of IUGR induced by prenatal caffeine ingestion

International Nuclear Information System (INIS)

Xu, D.; Wu, Y.; Liu, F.; Liu, Y.S.; Shen, L.; Lei, Y.Y.; Liu, J.; Ping, J.; Qin, J.; Zhang, C.; Chen, L.B.; Magdalou, J.; Wang, H.

2012-01-01

Caffeine is a definite factor of intrauterine growth retardation (IUGR). Previously, we have confirmed that prenatal caffeine ingestion inhibits the development of hypothalamic–pituitary–adrenal (HPA) axis, and alters the glucose and lipid metabolism in IUGR fetal rats. In this study, we aimed to verify a programmed alteration of neuroendocrine metabolism in prenatal caffeine ingested-offspring rats. The results showed that prenatal caffeine (120 mg/kg.day) ingestion caused low body weight and high IUGR rate of pups; the concentrations of blood adrenocorticotropic hormone (ACTH) and corticosterone in caffeine group were significantly increased in the early postnatal period followed by falling in late stage; the level of blood glucose was unchanged, while blood total cholesterol (TCH) and triglyceride (TG) were markedly enhanced in adult. After chronic stress, the concentrations and the gain rates of blood ACTH and corticosterone were obviously increased, meanwhile, the blood glucose increased while the TCH and TG decreased in caffeine group. Further, the hippocampal mineralocorticoid receptor (MR) expression in caffeine group was initially decreased and subsequently increased after birth. After chronic stress, the 11β-hydroxysteroid dehydrogenase-1, glucocorticoid receptor (GR), MR as well as the MR/GR ratio were all significantly decreased. These results suggested that prenatal caffeine ingestion induced the dysfunction of HPA axis and associated neuroendocrine metabolic programmed alteration in IUGR offspring rats, which might be related with the functional injury of hippocampus. These observations provide a valuable experimental basis for explaining the susceptibility of IUGR offspring to metabolic syndrome and associated diseases. -- Highlights: ► Prenatal caffeine ingestion induced HPA axis dysfunction in IUGR offspring rats. ► Caffeine induced a neuroendocrine metabolic programmed alteration in offspring rats. ► Caffeine induced a functional injury

Transient Stress Intensity Factors of Functionally Graded Hollow Cylinders with Internal Circumferential Cracks

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Iman Eshraghi

Full Text Available Abstract In this paper, transient thermomechanical stress intensity factors for functionally graded cylinders with complete internal circumferential cracks are obtained using the weight function method. The finite difference method is used to calculate the time dependent temperature distribution and thermal stresses along the cylinder thickness. Furthermore, finite element analysis is performed to determine the weight function coefficients and to investigate the accuracy of the predicted stress intensity factors from the weight functions. Variation of the stress intensity factors with time and effects of the material gradation on the results are investigated, as well. It is shown that the proposed technique can be used to accurately predict transient thermomechanical stress intensity factors for functionally graded cylinders with arbitrary material gradation.

Maternal early-life trauma and affective parenting style: the mediating role of HPA-axis function.

Science.gov (United States)

Juul, Sarah H; Hendrix, Cassandra; Robinson, Brittany; Stowe, Zachary N; Newport, D Jeffrey; Brennan, Patricia A; Johnson, Katrina C

2016-02-01

A history of childhood trauma is associated with increased risk for psychopathology and interpersonal difficulties in adulthood and, for those who have children, impairments in parenting and increased risk of negative outcomes in offspring. Physiological and behavioral mechanisms are poorly understood. In the current study, maternal history of childhood trauma was hypothesized to predict differences in maternal affect and HPA axis functioning. Mother-infant dyads (N = 255) were assessed at 6 months postpartum. Mothers were videotaped during a 3-min naturalistic interaction, and their behavior was coded for positive, neutral, and negative affect. Maternal salivary cortisol was measured six times across the study visit, which also included an infant stressor paradigm. Results showed that childhood trauma history predicted increased neutral affect and decreased mean cortisol in the mothers and that cortisol mediated the association between trauma history and maternal affect. Maternal depression was not associated with affective measures or cortisol. Results suggest that early childhood trauma may disrupt the development of the HPA axis, which in turn impairs affective expression during mother-infant interactions in postpartum women. Interventions aimed at treating psychiatric illness in postpartum women may benefit from specific components to assess and treat trauma-related symptoms and prevent secondary effects on parenting.

Wearing red for signaling: the heme-bach axis in heme metabolism, oxidative stress response and iron immunology.

Science.gov (United States)

Igarashi, Kazuhiko; Watanabe-Matsui, Miki

2014-04-01

The connection between gene regulation and metabolism is an old issue that warrants revisiting in order to understand both normal as well as pathogenic processes in higher eukaryotes. Metabolites affect the gene expression by either binding to transcription factors or serving as donors for post-translational modification, such as that involving acetylation and methylation. The focus of this review is heme, a prosthetic group of proteins that includes hemoglobin and cytochromes. Heme has been shown to bind to several transcription factors, including Bach1 and Bach2, in higher eukaryotes. Heme inhibits the transcriptional repressor activity of Bach1, resulting in the derepression of its target genes, such as globin in erythroid cells and heme oxygenase-1 in diverse cell types. Since Bach2 is important for class switch recombination and somatic hypermutation of immunoglobulin genes as well as regulatory and effector T cell differentiation and the macrophage function, the heme-Bach2 axis may regulate the immune response as a signaling cascade. We discuss future issues regarding the topic of the iron/heme-gene regulation network based on current understanding of the heme-Bach axis, including the concept of "iron immunology" as the synthesis of the iron metabolism and the immune response.

A discrete stress-strength interference model based on universal generating function

International Nuclear Information System (INIS)

An Zongwen; Huang Hongzhong; Liu Yu

2008-01-01

Continuous stress-strength interference (SSI) model regards stress and strength as continuous random variables with known probability density function. This, to some extent, results in a limitation of its application. In this paper, stress and strength are treated as discrete random variables, and a discrete SSI model is presented by using the universal generating function (UGF) method. Finally, case studies demonstrate the validity of the discrete model in a variety of circumstances, in which stress and strength can be represented by continuous random variables, discrete random variables, or two groups of experimental data

Autobiographical memory functions and posttraumatic stress symptoms across adulthood

DEFF Research Database (Denmark)

del Palacio Gonzalez, Adriana; Watson, Lynn Ann; Berntsen, Dorthe

2018-01-01

. In this study, we examined the unique relationship between autobiographical memory functions and posttraumatic stress symptoms (PTSS) and whether such relationships varied with age across adulthood. A representative sample of 1040 adult Danes (20–70 years old) reported the frequency with which they recall......Previous research has documented robust individual differences in the functions served by autobiographical memories, and shown that different autobiographical memory functions are related to both positive and negative indicators of psychological well-being, and that their frequency varies with age...... autobiographical memories for different purposes as well as their level of posttraumatic stress disorder (PTSD) symptoms. Higher reflective and ruminative functions, as well as lower social function, predicted higher levels of PTSS. There were no moderating effects of age. The results suggest that although...

Sex-specific association between functional neuropeptide S receptor gene (NPSR1) variants and cortisol and central stress responses.

Science.gov (United States)

Streit, Fabian; Akdeniz, Ceren; Haddad, Leila; Kumsta, Robert; Entringer, Sonja; Frank, Josef; Yim, Ilona S; Zänkert, Sandra; Witt, Stephanie H; Kirsch, Peter; Rietschel, Marcella; Wüst, Stefan

2017-02-01

The brain neuropeptide S (NPS) system has recently generated substantial interest and may be of major relevance for central stress regulation. The NPS receptor (NPSR1) is highly expressed in the limbic system, exogenous NPS exerts pronounced anxiolytic and fear-attenuating effects in rodents and extensive close crosstalk between the NPS system and the hypothalamic-pituitary-adrenal (HPA) axis has been demonstrated. In humans, associations between NPSR1 variants and anxiety and panic disorder, as well as amygdala responsiveness to fear- relevant faces and prefrontal cortex activity in a fear conditioning paradigm have been reported. Moreover, a NPSR1 sequence variant was found to be associated with cortisol stress responses in males. Here, we performed a haplotype-based analysis covering three functional NPSR1 single nucleotide polymorphisms in the promoter (rs2530547), in exon 3 (rs324981) and exon 6 (rs727162) in 277 healthy subjects who were exposed to the Trier Social Stress Test (TSST). A significant sex-specific association with salivary cortisol responses to acute psychosocial stress was detected for the common TTC haplotype 2 (frequency of about 20%). In an additional study using an imaging genetics approach, 65 healthy subjects were exposed to a stress paradigm for scanner environments (“ScanSTRESS”). We found a significant and, again, sex-specific interaction between rs324981 (whose minor T-allele is harbored by haplotype 2) and the neural stress response in a cluster close to the parahippocampal gyrus (whole brain corrected). Moreover, as in the TSST sample, NPSR1 variation was associated with salivary cortisol responses (on a trend level) in a sex-specific way. In summary, our preliminary findings in two independent cohorts exposed to different stress paradigms suggest that the NPS system significantly influences acute stress responses and that sequence variation in NPSR1 may contribute to sex differences in stress regulation. Copyright © 2016

The Role of Stress Exposure and Family Functioning in Internalizing Outcomes of Urban Families.

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Sheidow, Ashli J; Henry, David B; Tolan, Patrick H; Strachan, Martha K

2014-11-01

Although research suggests that stress exposure and family functioning are associated with internalizing problems in adolescents and caregivers, surprisingly few studies have investigated the mechanisms that underlie this association. To determine whether family functioning buffers the development of internalizing problems in stress-exposed families, we assessed the relation between stress exposure, family functioning, and internalizing symptoms among a large sample of inner-city male youth and their caregivers living in poverty across five waves of data collection. We hypothesized that stress exposure and family functioning would predict development of subsequent youth and caregiver internalizing problems and that family functioning would moderate this relation, with higher functioning families demonstrating greater resiliency to stress exposure. We used a longitudinal, prospective design to evaluate whether family functioning (assessed at waves one through four) activated or buffered the effects of stress exposure (assessed at wave one) on subsequent internalizing symptoms (assessed at waves four and five). Stress from Developmental Transitions and family functioning were significant predictors of depressive symptoms and anxiety in youth; however, family functioning did not moderate the relation. Family functioning mediated the relation between stress from Daily Hassles and internalizing outcomes suggesting that poor parenting practices, low structure, and low emotional cohesion activate depression and anxiety in youth exposed to chronic and frequent everyday stressors. Surprisingly, only family functioning predicted depressive symptoms in caregivers. Results validate the use of a comprehensive, multi-informant assessment of stress when investigating internalizing outcomes in youth and support using family-based interventions in the treatment and prevention of internalizing.

New animal model of emotional stress: Behavioral, neuroendocrine and immunological consequences

Institute of Scientific and Technical Information of China (English)

LIN Wenjuan; WANG Weiwen; SHAO Feng

2003-01-01

This report describes a new model of emotional stress, which was induced by randomly giving an empty water bottle to rats during watering periods per day for 14 consecutive days. The behavioral, endocrinological and immunological consequences were investigated. The data showed that the emotional stress activated both the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system, leading to the increased blood levels of corticosterone and catecholamine. It also elicited attacking and exploring behavior, suppressed the immune function of the rats, including leukocyte counts, weight of the spleen, and the level of specific anti-ovalbumin IgG antibody production. Presenting no water and no empty bottle to rats only evoked the exploring behavior, increased the corticosterone level and decreased the leukocyte counts. These findings demonstrate a role of psychological factors on behavioral, endocrinological and immunological functioning. The animal model described in the present study may serve as an analogue mimicking emotional stress experienced in humans (e.g. anger and/or anxiety), and may be useful for further studying the complex relationships among emotional stress, behavior, and immune function.

Resveratrol ameliorates chronic unpredictable mild stress-induced depression-like behavior: involvement of the HPA axis, inflammatory markers, BDNF, and Wnt/β-catenin pathway in rats

Directory of Open Access Journals (Sweden)

Yang X

2017-10-01

Full Text Available Xin-Hua Yang,1 Su-Qi Song,2 Yun Xu3 1Department of Pharmacy, Hefei Eighth People’s Hospital, Hefei, 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, 3Faculty of Pharmacy, Anhui Medical University, Hefei, China Abstract: Classic antidepressant drugs are modestly effective across the population and most are associated with intolerable side effects. Recently, numerous lines of evidence suggest that resveratrol (RES, a natural polyphenol, possesses beneficial therapeutic activity for depression. The aim of the present study was to explore whether RES exhibits an antidepressant-like effect in a depression model and to explore the possible mechanism. A depression model was established via chronic unpredictable mild stress (CUMS, after which the model rats in the RES and fluoxetine groups received a daily injection of RES or fluoxetine, respectively. The sucrose preference test, open field test, and forced swimming test were used to explore the antidepressant-like effects of RES. The activity of the hypothalamic–pituitary–adrenal (HPA axis was evaluated by detecting the plasma corticosterone concentration and hypothalamic mRNA expression of corticotrophin-releasing hormone. The plasma interleukin-6 (IL-6, C-reactive protein (CRP, and tumor necrosis factor-α (TNF-α concentrations were measured by enzyme-linked immunosorbent assay. Hippocampal protein expression of brain-derived neurotrophic factor (BDNF and the Wnt/β-catenin pathway were analyzed by western blot. The results showed that RES relieved depression-like behavior of CUMS rats, as indicated by the increased sucrose preference and the decreased immobile time. Rats that received RES treatment exhibited reduced plasma corticosterone levels and corticotrophin-releasing hormone mRNA expression in the hypothalamus, suggesting that the hyperactivity of the HPA axis in CUMS rats was reversed by RES. Moreover, after RES treatment, the rats exhibited increased

Stress influencing production and welfare in farmed mink

DEFF Research Database (Denmark)

Malmkvist, Jens

2012-01-01

Results linking stress, production and welfare in farmed mink, with special focus on the hypothalamic-pituitary-adrenal (HPA)-axis, are presented. Interpretation of stress responses are discussed, combining context, neuroendocrine and behavioural indicators. Results from the development and valid......Results linking stress, production and welfare in farmed mink, with special focus on the hypothalamic-pituitary-adrenal (HPA)-axis, are presented. Interpretation of stress responses are discussed, combining context, neuroendocrine and behavioural indicators. Results from the development...... animals and whether fur-chewing/stereotypic behaviour is associated with hippocampal neurogenesis in mink. Perspectives and suggested future research aiming to improve production and welfare in farmed mink are given....

The stress-buffering effects of functional social support on ambulatory blood pressure.

Science.gov (United States)

Bowen, Kimberly S; Uchino, Bert N; Birmingham, Wendy; Carlisle, McKenzie; Smith, Timothy W; Light, Kathleen C

2014-11-01

Social support is a reliable predictor of cardiovascular health. According to the buffering hypothesis, stress is 1 mechanism by which support is able to affect physiological processes. However, most of the experimental evidence for the hypothesis comes from laboratory studies. Ambulatory blood pressure (ABP) protocols examine participants in their natural environment, where they are more likely to encounter personally relevant real-world stressors. Furthermore, prior work shows that examining support by its specific functional components reveals additional independent links to health. The current study aimed to examine the stress-buffering effects of functional social support on ABP. One hundred eighty-eight participants completed a 1-day ABP assessment along with measures of functional social support and both global perceived stress and momentary stress at time of reading. RESULTS indicated main effects for both stress measures. Global support, emotional, tangible, and informational support only moderated the effects of momentary stress, but not global stress, in predicting ABP. Informational support was the most consistent stress-buffering predictor of ABP, predicting both ambulatory systolic and diastolic blood pressure. The predicted values in ABP for informational support achieved health-relevant differences, emphasizing the value of examining functional support beyond global support alone. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Stress moderates the relationships between problem-gambling severity and specific psychopathologies.

Science.gov (United States)

Ronzitti, Silvia; Kraus, Shane W; Hoff, Rani A; Potenza, Marc N

2018-01-01

The purpose of this study was to examine the extent to which stress moderated the relationships between problem-gambling severity and psychopathologies. We analyzed Wave-1 data from 41,869 participants of the National Epidemiologic Survey of Alcohol and Related Conditions (NESARC). Logistic regression showed that as compared to a non-gambling (NG) group, individuals at-risk gambling (ARG) and problem gambling (PPG) demonstrated higher odds of multiple Axis-I and Axis-II disorders in both high- and low-stress groups. Interactions odds ratios were statistically significant for stress moderating the relationships between at-risk gambling (versus non-gambling) and Any Axis-I and Any Axis-II disorder, with substance-use and Cluster-A and Cluster-B disorders contributing significantly. Some similar patterns were observed for pathological gambling (versus non-gambling), with stress moderating relationships with Cluster-B disorders. In all cases, a stronger relationship was observed between problem-gambling severity and psychopathology in the low-stress versus high-stress groups. The findings suggest that perceived stress accounts for some of the variance in the relationship between problem-gambling severity and specific forms of psychopathology, particularly with respect to lower intensity, subsyndromal levels of gambling. Findings suggest that stress may be particularly important to consider in the relationships between problem-gambling severity and substance use and Cluster-B disorders. Published by Elsevier B.V.

Depersonalization experiences in undergraduates are related to heightened stress cortisol responses.

Science.gov (United States)

Giesbrecht, Timo; Smeets, Tom; Merckelbach, Harald; Jelicic, Marko

2007-04-01

The relationship between dissociative tendencies, as measured with the Dissociative Experiences Scale and its amnesia, absorption/imaginative involvement, and depersonalization/derealization subscales, and HPA axis functioning was studied in 2 samples of undergraduate students (N = 58 and 67). Acute stress was induced by means of the Trier Social Stress Test. Subjective and physiological stress (i.e., cortisol) responses were measured. Individuals high on the depersonalization/derealization subscale of the Dissociative Experiences Scale exhibited more pronounced cortisol responses, while individuals high on the absorption subscale showed attenuated responses. Interestingly, subjective stress experiences, as indicated by the Tension-Anxiety subscale of the Profile of Mood States, were positively related to trait dissociation. The present findings illustrate how various types of dissociation (i.e., depersonalization/derealization, absorption) are differentially related to cortisol stress responses.

Stress and Female Reproductive System: Disruption of Corticotropin-Releasing Hormone/Opiate Balance by Sympathetic Nerve Traffic

Directory of Open Access Journals (Sweden)

Farideh Zafari Zangeneh

2009-09-01

Full Text Available Nowadays stress is an integral part of everyday living and the physiological and behavioral consequences of exposure to stressful situations have been extensively studied for decades. The stress response is a necessary mechanism but disrupts homeostatic process and it is sub served by a complex system located in both the central nervous system (CNS and the periphery. Stressor-induced activation of the hypothalamus–pituitary–adrenal (HPA axis and the sympathetic nervous system (SNS results in a series of neural and endocrine adaptations known as the "stress response" or "stress cascade." The stress cascade is responsible for allowing the body to make the necessary physiological and metabolic changes required to cope with the demands of a homeostatic challenge. Normal activation of the HPA axis is essential for reproduction, growth, metabolic homeostasis, and responses to stress and they are critical for adapting to changes in the external environment. The regulation of gonadal function in men and women is under the control of the HPA. This regulation is complex and sex steroids are important regulators of GnRH and gonadotropin release through classical feedback mechanisms in the hypothalamus and the pituitary. The present overview focuses on the neuroendocrine infrastructure of the adaptive response to stress and its effects on the female reproductive system. 

Stress-induced cognitive dysfunction: hormone-neurotransmitter interactions in the prefrontal cortex

Directory of Open Access Journals (Sweden)

Rebecca M Shansky

2013-04-01

Full Text Available The mechanisms and neural circuits that drive emotion and cognition are inextricably linked. Activation of the hypothalamic-pituitary-adrenal (HPA axis as a result of stress or other causes of arousal initiates a flood of hormone and neurotransmitter release throughout the brain, affecting the way we think, decide, and behave. This review will focus on factors that influence the function of the prefrontal cortex (PFC, a brain region that governs higher-level cognitive processes and executive function. The PFC becomes markedly impaired by stress, producing measurable deficits in working memory. These deficits arise from the interaction of multiple neuromodulators, including glucocorticoids, catecholamines, and gonadal hormones; here we will discuss the non- human primate and rodent literature that has furthered our understanding of the circuitry, receptors, and signaling cascades responsible for stress-induced prefrontal dysfunction.

Fetal alcohol programming of hypothalamic proopiomelanocortin system by epigenetic mechanisms and later life vulnerability to stress.

Science.gov (United States)

Bekdash, Rola; Zhang, Changqing; Sarkar, Dipak

2014-09-01

Hypothalamic proopiomelanocortin (POMC) neurons, one of the major regulators of the hypothalamic-pituitary-adrenal (HPA) axis, immune functions, and energy homeostasis, are vulnerable to the adverse effects of fetal alcohol exposure (FAE). These effects are manifested in POMC neurons by a decrease in Pomc gene expression, a decrement in the levels of its derived peptide β-endorphin and a dysregulation of the stress response in the adult offspring. The HPA axis is a major neuroendocrine system with pivotal physiological functions and mode of regulation. This system has been shown to be perturbed by prenatal alcohol exposure. It has been demonstrated that the perturbation of the HPA axis by FAE is long-lasting and is linked to molecular, neurophysiological, and behavioral changes in exposed individuals. Recently, we showed that the dysregulation of the POMC system function by FAE is induced by epigenetic mechanisms such as hypermethylation of Pomc gene promoter and an alteration in histone marks in POMC neurons. This developmental programming of the POMC system by FAE altered the transcriptome in POMC neurons and induced a hyperresponse to stress in adulthood. These long-lasting epigenetic changes influenced subsequent generations via the male germline. We also demonstrated that the epigenetic programming of the POMC system by FAE was reversed in adulthood with the application of the inhibitors of DNA methylation or histone modifications. Thus, prenatal environmental influences, such as alcohol exposure, could epigenetically modulate POMC neuronal circuits and function to shape adult behavioral patterns. Identifying specific epigenetic factors in hypothalamic POMC neurons that are modulated by fetal alcohol and target Pomc gene could be potentially useful for the development of new therapeutic approaches to treat stress-related diseases in patients with fetal alcohol spectrum disorders. Copyright © 2014 by the Research Society on Alcoholism.

Despite higher glucocorticoid levels and stress responses in female rats, both sexes exhibit similar stress-induced changes in hippocampal neurogenesis.

Science.gov (United States)

Hulshof, Henriëtte J; Novati, Arianna; Luiten, Paul G M; den Boer, Johan A; Meerlo, Peter

2012-10-01

Sex differences in stress reactivity may be one of the factors underlying the increased sensitivity for the development of psychopathologies in women. Particularly, an increased hypothalamic-pituitary-adrenal (HPA) axis reactivity in females may exacerbate stress-induced changes in neuronal plasticity and neurogenesis, which in turn may contribute to an increased sensitivity to psychopathology. The main aim of the present study was to examine male-female differences in stress-induced changes in different aspects of hippocampal neurogenesis, i.e. cell proliferation, differentiation and survival. Both sexes were exposed to a wide variety of stressors, where after differences in HPA-axis reactivity and neurogenesis were assessed. To study the role of oestradiol in potential sex differences, ovariectomized females received low or high physiological oestradiol level replacement pellets. The results show that females in general have a higher basal and stress-induced HPA-axis activity than males, with minimal differences between the two female groups. Cell proliferation in the dorsal hippocampus was significantly higher in high oestradiol females compared to low oestradiol females and males, while doublecortin (DCX) expression as a marker of cell differentiation was significantly higher in males compared to females, independent of oestradiol level. Stress exposure did not significantly influence cell proliferation or survival of new cells, but did reduce DCX expression. In conclusion, despite the male-female differences in HPA-axis activity, the effect of repeated stress exposure on hippocampal cell differentiation was not significantly different between sexes. Copyright © 2012 Elsevier B.V. All rights reserved.

Surface correlation function analysis of high resolution scattering data from mirrored surfaces obtained using a triple-axis X-ray diffractometer

DEFF Research Database (Denmark)

Christensen, Finn Erland; Hornstrup, Allan; Schnopper, H. W.

1988-01-01

methods is that they are bandwidth-limited. A crucial point in the analysis of data is, therefore, to specify accurately the wavelength bandwidth limitation and to determine the surface autocorrelation function within this bandwidth. The authors present a number of scattering measurements obtained using...... a triple-axis perfect-crystal X-ray diffractometer and the results of an autocorrelation function analysis. Furthermore, they present some measurements of integrated reflectivity, which they believe provide evidence for microroughness in the range from a few angstroms to tens of microns...

Comparison of the effects of single and daily repeated immobilization stress on resting activity and heterotypic sensitization of the hypothalamic-pituitary-adrenal axis.

Science.gov (United States)

Daviu, Núria; Rabasa, Cristina; Nadal, Roser; Armario, Antonio

2014-03-01

Acute exposure to severe stressors causes marked activation of the hypothalamic-pituitary-adrenal (HPA) axis that is reflected on the day after higher resting levels of HPA hormones and sensitization of the HPA response to novel (heterotypic) stressors. However, whether a single exposure to a severe stressor or daily repeated exposure to the same (homotypic) stressor modifies these responses to the same extent has not been studied. In this experiment, we studied this issue in adult male Sprague-Dawley rats daily exposed for seven days to a severe stressor such as immobilization on boards (IMO). A first exposure to 1 h IMO resulted in a marked activation of the HPA axis as reflected in plasma levels of adrenocorticotropic hormone (ACTH) and corticosterone, and such activation was significantly reduced after the seventh IMO. On the day after the first IMO, higher resting levels of ACTH and corticosterone and sensitization of their responses to a short exposure to an open-field (OF) were observed, together with a marked hypoactivity in this environment. Repeated exposure to IMO partially reduced hypoactivity, the increase in resting levels of HPA hormones and the ACTH responsiveness to the OF on the day after the last exposure to IMO. In contrast, corticosterone response was gradually increased, suggesting partial dissociation from ACTH. These results indicate that daily repeated exposure to the same stressor partially reduced the HPA response to the homotypic stressor as well as the sensitization of HPA axis activity observed the day after chronic stress cessation.

Enhancement of BDNF Concentration and Restoration of the Hypothalamic-Pituitary-Adrenal Axis Accompany Reduced Depressive-Like Behaviour in Stressed Ovariectomised Rats Treated with Either Tualang Honey or Estrogen

Directory of Open Access Journals (Sweden)

Badriya Al-Rahbi

2014-01-01

Full Text Available A possible interaction between glucocorticoids and estrogen-induced increases in brain-derived-neurotrophic factor (BDNF expression in enhancing depressive-like behaviour has been documented. Here we evaluated the effects of Tualang honey, a phytoestrogen, and 17β-estradiol (E2 on the depressive-like behaviour, stress hormones, and BDNF concentration in stressed ovariectomised (OVX rats. The animals were divided into six groups: (i nonstressed sham-operated control, (ii stressed sham-operated control, (iii nonstressed OVX, (iv stressed OVX, (v stressed OVX treated with E2 (20 μg daily, sc, and (vi stressed OVX treated with Tualang honey (0.2 g/kg body weight daily, orally. Two months after surgery, the animals were subjected to social instability stress procedure followed by forced swimming test. Struggling time, immobility time, and swimming time were scored. Serum adrenocorticotropic hormone (ACTH and corticosterone levels, and the BDNF concentration were determined using commercially available ELISA kits. Stressed OVX rats displayed increased depressive-like behaviour with significantly increased serum ACTH and corticosterone levels, while the BDNF concentration was significantly decreased compared to other experimental groups. These changes were notably reversed by both E2 and Tualang honey. In conclusion, both Tualang honey and E2 mediate antidepressive-like effects in stressed OVX rats, possibly acting via restoration of hypothalamic-pituitary-adrenal axis and enhancement of the BDNF concentration.

Theta variation and spatiotemporal scaling along the septotemporal axis of the hippocampus

Directory of Open Access Journals (Sweden)

Lauren L Long

2015-03-01

Full Text Available Hippocampal theta has been related to locomotor speed, attention, anxiety, sensorimotor integration and memory among other emergent phenomena. One difficulty in understanding the function of theta is that the hippocampus (HPC modulates voluntary behavior at the same time that it processes sensory input. Both functions are correlated with characteristic changes in theta indices. The current review highlights a series of studies examining theta local field potential (LFP signals across the septotemporal or longitudinal axis of the HPC. While the theta signal is coherent throughout the entirety of the HPC, the amplitude, but not the frequency, of theta varies significantly across its three-dimensional expanse. We suggest that the theta signal offers a rich vein of information about how distributed neuronal ensembles support emergent function. Further, we speculate that emergent function across the long axis varies with respect to spatiotemporal scale. Thus, septal hippocampus processes details of the proximal spatiotemporal environment while more temporal aspects process larger spaces and wider time-scales. The degree to which emergent functions are supported by the synchronization of theta across the septotemporal axis is an open question. Our working model is that theta synchrony serves to bind ensembles representing varying resolutions of spatiotemporal information at interdependent septotemporal areas of the HPC. Such synchrony and cooperative interactions along the septotemporal axis likely support memory formation and subsequent consolidation and retrieval.

Effects of the Cognitive-Behavioral Therapy for Stress Management on Executive Function Components.

Science.gov (United States)

Santos-Ruiz, Ana; Robles-Ortega, Humbelina; Pérez-García, Miguel; Peralta-Ramírez, María Isabel

2017-02-13

This study aims to determine whether it is possible to modify executive function in stressed individuals by means of cognitive-behavioral therapy for stress management. Thirty-one people with high levels of perceived stress were recruited into the study (treatment group = 18; wait-list group = 13). The treatment group received 14 weeks of stress management program. Psychological and executive function variables were evaluated in both groups pre and post-intervention. The treatment group showed improved psychological variables of perceived stress (t = 5.492; p = .001), vulnerability to stress (t = 4.061; p = .001) and superstitious thinking (t = 2.961; p = .009). Likewise, the results showed statistically significant differences in personality variables related to executive function, positive urgency (t = 3.585; p = .002) and sensitivity to reward (t = -2.201; p = .042), which improved after the therapy. These variables showed a moderate to high effect size (oscillates between 1.30 for perceived stress and .566 for sensitivity to reward). The cognitive-behavioral therapy for stress management may be an appropriate strategy for improving personality construct components related to executive function, however effects of the therapy are not showed on performance on the tests of executive function applied, as presented studies previous.

Investigating the Potential of Using Off-Axis 3D Woven Composites in Composite Joints’ Applications

KAUST Repository

Saleh, Mohamed Nasr; Wang, Ying; Yudhanto, Arief; Joesbury, Adam; Potluri, Prasad; Lubineau, Gilles; Soutis, Constantinos

2016-01-01

The effect of circular notch has been evaluated for three different architectures of three-dimensional (3D) carbon fibre woven composites (orthogonal, ORT; layer-to-layer, LTL; angle interlock, AI) through open-hole quasi-static tension and double-lap bearing strength tests in the off-axis (45°) direction. Damage characterisation is monitored using Digital Image correlation (DIC) for open-hole testing and X-ray Computed Tomography (CT) for double-lap bearing strength test. The off-axis notched 3D woven composites exhibits minor reduction (less than 10 %) of the notched strength compared to the un-notched strength. DIC strain contour clearly show stress/strain localisation regions around the hole periphery and stress/strain redistribution away from the whole due to the z-binder existence, especially for ORT architecture. Up to 50 % bearing strain, no significant difference in the bearing stress/bearing strain response is observed. However when ORT architecture was loaded up to failure, it demonstrates higher strain to failure (~140 %) followed by AI (~105 %) and lastly LTL (~85 %). X-ray CT scans reveal the effect of the z-binder architecture on damage evolution and delamination resistance. The study suggests that off-axis loaded 3D woven composites, especially ORT architecture, has a great potential of overcoming the current challenges facing composite laminates when used in composite joints’ applications. © 2016 The Author(s)

Investigating the Potential of Using Off-Axis 3D Woven Composites in Composite Joints’ Applications

KAUST Repository

Saleh, Mohamed Nasr

2016-09-26

The effect of circular notch has been evaluated for three different architectures of three-dimensional (3D) carbon fibre woven composites (orthogonal, ORT; layer-to-layer, LTL; angle interlock, AI) through open-hole quasi-static tension and double-lap bearing strength tests in the off-axis (45°) direction. Damage characterisation is monitored using Digital Image correlation (DIC) for open-hole testing and X-ray Computed Tomography (CT) for double-lap bearing strength test. The off-axis notched 3D woven composites exhibits minor reduction (less than 10 %) of the notched strength compared to the un-notched strength. DIC strain contour clearly show stress/strain localisation regions around the hole periphery and stress/strain redistribution away from the whole due to the z-binder existence, especially for ORT architecture. Up to 50 % bearing strain, no significant difference in the bearing stress/bearing strain response is observed. However when ORT architecture was loaded up to failure, it demonstrates higher strain to failure (~140 %) followed by AI (~105 %) and lastly LTL (~85 %). X-ray CT scans reveal the effect of the z-binder architecture on damage evolution and delamination resistance. The study suggests that off-axis loaded 3D woven composites, especially ORT architecture, has a great potential of overcoming the current challenges facing composite laminates when used in composite joints’ applications. © 2016 The Author(s)

Stress tolerances of nullmutants of function-unknown genes encoding menadione stress-responsive proteins in Aspergillus nidulans.

Science.gov (United States)

Leiter, Éva; Bálint, Mihály; Miskei, Márton; Orosz, Erzsébet; Szabó, Zsuzsa; Pócsi, István

2016-07-01

A group of menadione stress-responsive function-unkown genes of Aspergillus nidulans (Locus IDs ANID_03987.1, ANID_06058.1, ANID_10219.1, and ANID_10260.1) was deleted and phenotypically characterized. Importantly, comparative and phylogenetic analyses of the tested A. nidulans genes and their orthologs shed light only on the presence of a TANGO2 domain with NRDE protein motif in the translated ANID_06058.1 gene but did not reveal any recognizable protein-encoding domains in other protein sequences. The gene deletion strains were subjected to oxidative, osmotic, and metal ion stress and, surprisingly, only the ΔANID_10219.1 mutant showed an increased sensitivity to 0.12 mmol l(-1) menadione sodium bisulfite. The gene deletions affected the stress sensitivities (tolerances) irregularly, for example, some strains grew more slowly when exposed to various oxidants and/or osmotic stress generating agents, meanwhile the ΔANID_10260.1 mutant possessed a wild-type tolerance to all stressors tested. Our results are in line with earlier studies demonstrating that the deletions of stress-responsive genes do not confer necessarily any stress-sensitivity phenotypes, which can be attributed to compensatory mechanisms based on other elements of the stress response system with overlapping functions. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Can variation in hypothalamic-pituitary-adrenal (HPA-axis activity explain the relationship between depression and cognition in bipolar patients?

Directory of Open Access Journals (Sweden)

Marieke J van der Werf-Eldering

Full Text Available Dysregulation of the hypothalamic-pituitary-adrenal (HPA axis is thought to be associated with more mood symptoms and worse cognitive functioning. This study examined whether variation in HPA axis activity underlies the association between mood symptoms and cognitive functioning.In 65 bipolar patients cognitive functioning was measured in domains of psychomotor speed, speed of information processing, attentional switching, verbal memory, visual memory, executive functioning and an overall mean score. Severity of depression was assessed by the Inventory of Depressive Symptomatology-self rating version. Saliva cortisol measurements were performed to calculate HPA axis indicators: cortisol awakening response, diurnal slope, the evening cortisol level and the cortisol suppression on the dexamethasone suppression test. Regression analyses of depressive symptoms and cognitive functioning on each HPA axis indicator were performed. In addition we calculated percentages explanation of the association between depressive symptoms and cognition by HPA axis indicators. Depressive symptoms were associated with dysfunction in psychomotor speed, attentional switching and the mean score, as well as with attenuation in diurnal slope value. No association was found between HPA axis activity and cognitive functioning and HPA axis activity did not explain the associations between depressive symptoms and cognition.As our study is the first one in this field specific for bipolar patients and changes in HPA-axis activity did not seem to explain the association between severity of depressive symptoms and cognitive functioning in bipolar patients, future studies are needed to evaluate other factors that might explain this relationship.

Associations in the Course of Personality Disorders and Axis I Disorders Over Time

Science.gov (United States)

Shea, M. Tracie; Yen, Shirley; Pagano, Maria E.; Morey, Leslie C.; McGlashan, Thomas H.; Grilo, Carlos M.; Sanislow, Charles A.; Stout, Robert L.; Skodol, Andrew E.; Gunderson, John G.; Bender, Donna S.; Zanarini, Mary C.

2012-01-01

In this study, the authors examined time-varying associations between schizotypal (STPD), borderline (BPD), avoidant (AVPD), or obsessive–compulsive (OCPD) personality disorders and co-occurring Axis I disorders in 544 adult participants from the Collaborative Longitudinal Personality Disorders Study. The authors tested predictions of specific longitudinal associations derived from a model of crosscutting psychobiological dimensions (L. J. Siever & K. L. Davis, 1991) with participants with the relevant Axis I disorders. The authors assessed participants at baseline and at 6-, 12-, and 24-month follow-up evaluations. BPD showed significant longitudinal associations with major depressive disorder and posttraumatic stress disorder. AVPD was significantly associated with anxiety disorders (specifically social phobia and obsessive–compulsive disorder). Two of the four personality disorders under examination (STPD and OCPD) showed little or no association with Axis I disorders. PMID:15535783

Production of functional proteins: balance of shear stress and gravity

Science.gov (United States)

Goodwin, Thomas John (Inventor); Hammond, Timothy Grant (Inventor); Kaysen, James Howard (Inventor)

2011-01-01

A method for the production of functional proteins including hormones by renal cells in a three dimensional culturing process responsive to shear stress uses a rotating wall vessel. Natural mixture of renal cells expresses the enzyme 1-.alpha.-hydroxylase which can be used to generate the active form of vitamin D: 1,25-diOH vitamin D.sub.3. The fibroblast cultures and co-culture of renal cortical cells express the gene for erythropoietin and secrete erythropoietin into the culture supernatant. Other shear stress response genes are also modulated by shear stress, such as toxin receptors megalin and cubulin (gp280). Also provided is a method of treating an in-need individual with the functional proteins produced in a three dimensional co-culture process responsive to shear stress using a rotating wall vessel.

Shear stresses around circular cylindrical openings

NARCIS (Netherlands)

Hoogenboom, P.C.J.; Van Weelden, C.; Blom, C.M.B.

2010-01-01

In this paper stress concentrations are studied around circular cylindrical openings or voids in a linear elastic continuum. The loading is such that a uniform shear stress occurs in the continuum, which is disturbed by the opening. The shear stress is in the direction of the centre axis of the

Triple axis spectrometers

International Nuclear Information System (INIS)

Clausen, K.N.

1997-01-01

Conventional triple-axis neutron spectroscopy was developed by Brockhouse over thirty years ago' and remains today a versatile and powerful tool for probing the dynamics of condensed matter. The original design of the triple axis spectrometer is technically simple and probes momentum and energy space on a point-by-point basis. This ability to systematically probe the scattering function in a way which only requires a few angles to be moved under computer control and where the observed data in general can be analysed using a pencil and graph paper or a simple fitting routine, has been essential for the success of the method. These constraints were quite reasonable at the time the technique was developed. Advances in computer based data acquisition, neutron beam optics, and position sensitive area detectors have been gradually implemented on many triple axis spectrometer spectrometers, but the full potential of this has not been fully exploited yet. Further improvement in terms of efficiency (beyond point by point inspection) and increased sensitivity (use of focusing optics whenever the problem allows it) could easily be up to a factor of 10-20 over present instruments for many problems at a cost which is negligible compared to that of increasing the flux of the source. The real cost will be in complexity - finding the optimal set-up for a given scan and interpreting the data as the they are taken. On-line transformation of the data for an appropriate display in Q, ω space and analysis tools will be equally important for this task, and the success of these new ideas will crucially depend on how well we solve these problems. (author)

Glucocorticoid programming of neuroimmune function.

Science.gov (United States)

Walker, David J; Spencer, Karen A

2018-01-15

Throughout life physiological systems strive to maintain homeostasis and these systems are susceptible to exposure to maternal or environmental perturbations, particularly during embryonic development. In some cases, these perturbations may influence genetic and physiological processes that permanently alter the functioning of these physiological systems; a process known as developmental programming. In recent years, the neuroimmune system has garnered attention for its fundamental interactions with key hormonal systems, such as the hypothalamic pituitary adrenal (HPA) axis. The ultimate product of this axis, the glucocorticoid hormones, play a key role in modulating immune responses within the periphery and the CNS as part of the physiological stress response. It is well-established that elevated glucocorticoids induced by developmental stress exert profound short and long-term physiological effects, yet there is relatively little information of how these effects are manifested within the neuroimmune system. Pre and post-natal periods are prime candidates for manipulation in order to uncover the physiological mechanisms that underlie glucocorticoid programming of neuroimmune responses. Understanding the potential programming role of glucocorticoids may be key in uncovering vulnerable windows of CNS susceptibility to stressful experiences during embryonic development and improve our use of glucocorticoids as therapeutics in the treatment of neurodegenerative diseases. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Latino parent acculturation stress: Longitudinal effects on family functioning and youth emotional and behavioral health.

Science.gov (United States)

Lorenzo-Blanco, Elma I; Meca, Alan; Unger, Jennifer B; Romero, Andrea; Gonzales-Backen, Melinda; Piña-Watson, Brandy; Cano, Miguel Ángel; Zamboanga, Byron L; Des Rosiers, Sabrina E; Soto, Daniel W; Villamar, Juan A; Lizzi, Karina M; Pattarroyo, Monica; Schwartz, Seth J

2016-12-01

Latino parents can experience acculturation stressors, and according to the Family Stress Model (FSM), parent stress can influence youth mental health and substance use by negatively affecting family functioning. To understand how acculturation stressors come together and unfold over time to influence youth mental health and substance use outcomes, the current study investigated the trajectory of a latent parent acculturation stress factor and its influence on youth mental health and substance use via parent-and youth-reported family functioning. Data came from a 6-wave, school-based survey with 302 recent (stress loaded onto a latent factor of acculturation stress at each of the first 4 time points. Earlier levels of and increases in parent acculturation stress predicted worse youth-reported family functioning. Additionally, earlier levels of parent acculturation stress predicted worse parent-reported family functioning and increases in parent acculturation stress predicted better parent-reported family functioning. While youth-reported positive family functioning predicted higher self-esteem, lower symptoms of depression, and lower aggressive and rule-breaking behavior in youth, parent-reported family positive functioning predicted lower youth alcohol and cigarette use. Findings highlight the need for Latino youth preventive interventions to target parent acculturation stress and family functioning. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Leaf sodium accumulation facilitates salt stress adaptation and preserves photosystem functionality in salt stressed Ocimum basilicum

NARCIS (Netherlands)

Mancarella, S.; Orsini, F.; Oosten, van M.J.; Sanoubar, R.; Stanghellini, C.; Kondo, S.; Gianquinto, G.; Maggio, A.

2016-01-01

In this study, plant growth, water relations, ABA levels, ion accumulation patterns and chlorophyll fluorescence were functionally linked to salt stress tolerance of two basil cultivars (Napoletano and Genovese) with different stress sensitivity levels. Plants were treated with salty water at 0,

Anxiolytic effects of GLYX-13 in animal models of posttraumatic stress disorder-like behavior.

Science.gov (United States)

Jin, Zeng-Liang; Liu, Jin-Xu; Liu, Xu; Zhang, Li-Ming; Ran, Yu-Hua; Zheng, Yuan-Yuan; Tang, Yu; Li, Yun-Feng; Xiong, Jie

2016-09-01

In the present study, we investigated the effectiveness of GLYX-13, an NMDA receptor glycine site functional partial agonist, to alleviate the enhanced anxiety and fear response in both a mouse and rat model of stress-induced behavioral changes that might be relevant to posttraumatic stress disorder (PTSD). Studies over the last decades have suggested that the hyperactivity of hypothalamic-pituitary-adrenal (HPA) axis is one of the most consistent findings in stress-related disease. Herein, we used these animal models to further investigate the effect of GLYX-13 on the stress hormone levels and glucocorticoid receptor (GR) expression. We found that exposure to foot shock induced long-lasting behavioral deficiencies in mice, including freezing and anxiety-like behaviors, that were significantly ameliorated by the long-term administration of GLYX-13 (5 or 10 mg/kg). Our enzyme-linked immunosorbent assay results showed that long-term administration of GLYX-13 at behaviorally effective doses (5 or 10 mg/kg) significantly decreased the elevated serum levels of both corticosterone and its upstream stress hormone adrenocorticotropic hormone in rats subjected to the TDS procedure. These results suggest that GLYX-13 exerts a therapeutic effect on PTSD-like stress responding that is accompanied by (or associated with) modulation of the HPA axis, including inhibition of stress hormone levels and upregulation of hippocampal GR expression. © The Author(s) 2016.

Adolescent development, hypothalamic-pituitary-adrenal function, and programming of adult learning and memory.

Science.gov (United States)

McCormick, Cheryl M; Mathews, Iva Z

2010-06-30

Chronic exposure to stress is known to affect learning and memory in adults through the release of glucocorticoid hormones by the hypothalamic-pituitary-adrenal (HPA) axis. In adults, glucocorticoids alter synaptic structure and function in brain regions that express high levels of glucocorticoid receptors and that mediate goal-directed behaviour and learning and memory. In contrast to relatively transient effects of stress on cognitive function in adulthood, exposure to high levels of glucocorticoids in early life can produce enduring changes through substantial remodeling of the developing nervous system. Adolescence is another time of significant brain development and maturation of the HPA axis, thereby providing another opportunity for glucocorticoids to exert programming effects on neurocircuitry involved in learning and memory. These topics are reviewed, as is the emerging research evidence in rodent models highlighting that adolescence may be a period of increased vulnerability compared to adulthood in which exposure to high levels of glucocorticoids results in enduring changes in adult cognitive function. Copyright 2009 Elsevier Inc. All rights reserved.

Multi-Axis Thrust Measurements of the EO-1 Pulsed Plasma Thruster

Science.gov (United States)

Arrington, Lynn A.; Haag, Thomas W.

1999-01-01

Pulsed plasma thrusters are low thrust propulsive devices which have a high specific impulse at low power. A pulsed plasma thruster is currently scheduled to fly as an experiment on NASA's Earth Observing-1 satellite mission. The pulsed plasma thruster will be used to replace one of the reaction wheels. As part of the qualification testing of the thruster it is necessary to determine the nominal thrust as a function of charge energy. These data will be used to determine control algorithms. Testing was first completed on a breadboard pulsed plasma thruster to determine nominal or primary axis thrust and associated propellant mass consumption as a function of energy and then later to determine if any significant off-axis thrust component existed. On conclusion that there was a significant off-axis thrust component with the bread-board in the direction of the anode electrode, the test matrix was expanded on the flight hardware to include thrust measurements along all three orthogonal axes. Similar off-axis components were found with the flight unit.

Dual-hormone stress reactivity predicts downstream war-zone stress-evoked PTSD.

Science.gov (United States)

Josephs, Robert A; Cobb, Adam R; Lancaster, Cynthia L; Lee, Han-Joo; Telch, Michael J

2017-04-01

The crucial role of the hypothalamic-pituitary-adrenal axis (HPA) in stress-related homeostasis suggests dysregulated HPA involvement in the pathogenesis of post-traumatic stress disorder (PTSD), yet most studies examining linkages between HPA axis measures and PTSD have yielded null findings. One untested explanation for this inconsistency is a failure to account for simultaneous adrenal and gonadal influence. Here we tested the singular and interactive effects of cortisol (C R ) and testosterone (T R ) reactivity as moderators of war-zone stress evoked PTSD emergence in the war-zone. U.S. soldiers (N=120) scheduled for deployment to Iraq completed pre-deployment measures of C R and T R stress reactivity to a CO 2 inhalation challenge. Once deployed, monthly assessments of exposure to traumatic war-zone stressors and PTSD symptoms were collected via a web-based assessment system. Cortisol hypo-reactivity potentiated the pathogenic impact of war-zone stressors only in soldiers for whom the CO 2 challenge did not elevate testosterone, suggesting that the dual hormone stress reactivity profile of blunted cortisol and testosterone may confer increased risk for PTSD emergence by potentiating the pathogenic effects of war-zone stressors. Findings underscore the utility of assessing both HPA and HPG stress reactivity when assessing PTSD vulnerability and may help inform efforts for enhanced soldier screening and inoculation to war-zone stressors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

Science.gov (United States)

Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

2010-11-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

Early life stress determines the effects of glucocorticoids and stress on hippocampal function: Electrophysiological and behavioral evidence respectively.

Science.gov (United States)

Pillai, Anup G; Arp, Marit; Velzing, Els; Lesuis, Sylvie L; Schmidt, Mathias V; Holsboer, Florian; Joëls, Marian; Krugers, Harm J

2018-05-01

Exposure to early-life adversity may program brain function to prepare individuals for adaptation to matching environmental contexts. In this study we tested this hypothesis in more detail by examining the effects of early-life stress - induced by raising offspring with limited nesting and bedding material from postnatal days 2-9 - in various behavioral tasks and on synaptic function in adult mice. Early-life stress impaired adult performance in the hippocampal dependent low-arousing object-in-context recognition memory task. This effect was absent when animals were exposed to a single stressor before training. Early-life stress did not alter high-arousing context and auditory fear conditioning. Early-life stress-induced behavioral modifications were not associated with alterations in the dendritic architecture of hippocampal CA1 pyramidal neurons or principal neurons of the basolateral amygdala. However, early-life stress reduced the ratio of NMDA to AMPA receptor-mediated excitatory postsynaptic currents and glutamate release probability specifically in hippocampal CA1 neurons, but not in the basolateral amygdala. These ex vivo effects in the hippocampus were abolished by acute glucocorticoid treatment. Our findings support that early-life stress can hamper object-in-context learning via pre- and postsynaptic mechanisms that affect hippocampal function but these effects are counteracted by acute stress or elevated glucocorticoid levels. Copyright © 2018. Published by Elsevier Ltd.

Development of thermal stress screening method. Application of green function method

International Nuclear Information System (INIS)

Furuhashi, Ichiro; Shibamoto, Hiroshi; Kasahara, Naoto

2004-01-01

This work was achieved for the development of the screening method of thermal transient stresses in FBR components. We proposed an approximation method for evaluations of thermal stress under variable heat transfer coefficients (non-linear problems) using the Green functions of thermal stresses with constant heat transfer coefficients (linear problems). Detailed thermal stress analyses provided Green functions for a skirt structure and a tube-sheet of Intermediate Heat Exchanger. The upper bound Green functions were obtained by the analyses using those upper bound heat transfer coefficients. The medium and the lower bound Green functions were got by the analyses of those under medium and the lower bound heat transfer coefficients. Conventional evaluations utilized the upper bound Green functions. On the other hand, we proposed a new evaluation method by using the upper bound, medium and the lower bound Green functions. The comparison of above results gave the results as follows. The conventional evaluations were conservative and appropriate for the cases under one fluid thermal transient structure such as the skirt. The conventional evaluations were generally conservative for the complicated structures under two or more fluids thermal transients such as the tube-sheet. But the danger locations could exists for the complicated structures under two or more fluids transients, namely the conventional evaluations were non-conservative. The proposed evaluations gave good estimations for these complicated structures. Though above results, we have made the basic documents of the screening method of thermal transient stresses using the conventional method and the new method. (author)

[Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality].

Science.gov (United States)

Sidor, Anna; Köhler, Hubert; Cierpka, Manfred

2018-03-01

Impact of Socioeconomic Risk Exposure on Maternal Sensitivity, Stress and Family Functionality Parental stress exposure can influence the parent-child relationship, child development and child wellbeing in negative ways. The aim of this study was to investigate the impact of socio-economic risk exposure on the quality of the mother-child-interaction and family functionality. A sample of 294 mother-infant dyads at psychosocial risk was compared with a lower-risk, middle-class sample of 125 mother-infant-dyads in regard to maternal sensitivity/child's cooperation (CARE-Index), maternal stress (PSI-SF) and family functionality (FB-K). Lower levels of maternal sensitivity/child's cooperation and by trend also of the family functionality were found among the mothers from the at-risk sample in comparison to the low-risk sample. The level of maternal stress was similar in both samples. The results underpin the negative effects of a socio-economic risk exposure on the mother-child relationship. An early, sensitivity-focused family support could be encouraged to counteract the negative effects of early socioeconomic stress.

Determination of Hot-Carrier Distribution Functions in Uniaxially Stressed p-Type Germanium

DEFF Research Database (Denmark)

Christensen, Ove

1973-01-01

This paper gives a description of an experimental determination of distribution functions in k→ space of hot holes in uniaxially compressed germanium. The hot-carrier studies were made at 85°K at fields up to 1000 V/cm and uniaxial stresses up to 11 800 kg/cm2. The field and stress were always in...... probabilities with stress. A model based on the nonparabolicity of the upper p3 / 2 level is proposed for the negative differential conductivity in stressed p-type Ge....... function has been assumed. The parameters of the distribution function are then fitted to the experimental modulation. The calculation of absorption was performed numerically, using a four-band k→·p→ model. This model was checked for consistency by comparing with piezoabsorption measurements performed...... in thermal equilibrium. The average carrier energy calculated from the distribution function shows a fast increase with stress and almost saturates when the strain splitting of the two p3 / 2 levels reaches the optical-phonon energy. This saturation is interpreted in terms of the change in scattering...

NUR TRANSCRIPTION FACTORS IN STRESS AND ADDICTION

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Danae eCampos-Melo

2013-12-01

Full Text Available The Nur transcription factors Nur77 (NGFI-B, NR4A1, Nurr1 (NR4A2 and Nor-1 (NR4A3 are a sub-family of orphan members of the nuclear receptor superfamily. These transcription factors are products of immediate early genes, whose expression is rapidly and transiently induced in the central nervous system by several types of stimuli. Nur factors are present throughout the hypothalamus-pituitary-adrenal axis where are prominently induced in response to stress. Drugs of abuse and stress also induce the expression of Nur factors in nuclei of the motivation/reward circuit of the brain, indicating their participation in the process of drug addiction and in non-hypothalamic responses to stress. Repeated use of addictive drugs and chronic stress induce long-lasting dysregulation of the brain motivation/reward circuit, due to reprogramming of gene expression and enduring alterations in neuronal function. Here, we review the data supporting that Nur transcription factors are key players in the molecular basis of the dysregulation of neuronal circuits involved in chronic stress and addiction.

Static/dynamic Analysis and Optimization of Z-axis Stand of PCB CNC Drilling Machine*

Directory of Open Access Journals (Sweden)

Zhou Yanjun

2016-01-01

Full Text Available The finite element analysis is used for the static and dynamic analysis of the Z axis brace of PCB CNC drilling machine. With its results of maximum displacement deformation and von Mises stress and modal frequency, the defect of original design was found out. On such bases, a variety of optimization scheme is put forward and the best size of the Z axis brace is obtained by the performance comparison of the schemes. This method offers bases for the design and renovation of other machine tool components.

Anisotropic perpendicular axis magnetostriction in twinned TbxDy1-xFe1.95

International Nuclear Information System (INIS)

Teter, J.P.; Wun-Fogle, M.; Clark, A.E.; Mahoney, K.

1990-01-01

The longitudinal magnetostriction (Δl/l) for twinned Tb x Dy 1-x Fe 1.95 material, prepared by the free-standing float-zone method, has been previously measured and found to be very large (2000x10 -6 ) at room temperature. The magnetostrictions for the [111] and [1 bar 10] crystallographic axes perpendicular to the applied stress and magnetic-field [11 bar 2] direction are presented as functions of temperature, applied stress, and applied magnetic field. The temperature range is ±60 degree C centered about the anisotropy compensation temperature of Terfenol-D (+10 degree C). The stress ranges from 2 to 32 MPa and the magnetic field to ±2000 Oe. The temperature dependence of the perpendicular axes magnetostriction is similar to that of the conventional magnetostriction measured parallel to the [11 bar 2] growth axis. Relative values for the saturation magnetostriction exhibit a large anisotropy in the perpendicular direction, ranging from -117% for the [111] to +19% for the [1 bar 10] direction. This ratio stays constant as a function of temperature above the compensation temperature for a given prestress above 8 MPa. The largest absolute value of magnetostriction (2260x10 -6 ) occurs in the [111] direction at 10 degree C at a prestress pressure of 12 MPa. Above this temperature the magnetostriction falls at a rate of -8.5x10 -6 /degree C. The volume magnetostriction is shown to be small and highly sample dependent. All data is consistent with the parent-twin magnetization model and also the magnetostriction values along nonprincipal axes

Stress and brain functional changes in patients with Crohn's disease: A functional magnetic resonance imaging study.

Science.gov (United States)

Agostini, A; Ballotta, D; Righi, S; Moretti, M; Bertani, A; Scarcelli, A; Sartini, A; Ercolani, M; Nichelli, P; Campieri, M; Benuzzi, F

2017-10-01

In Crohn's disease (CD) patients, stress is believed to influence symptoms generation. Stress may act via central nervous system pathways to affect visceral sensitivity and motility thus exacerbating gastrointestinal symptoms. The neural substrate underpinning these mechanisms needs to be investigated in CD. We conducted an explorative functional magnetic resonance imaging (fMRI) study in order to investigate potential differences in the brain stress response in CD patients compared to controls. 17 CD patients and 17 healthy controls underwent a fMRI scan while performing a stressful task consisting in a Stroop color-word interference task designed to induce mental stress in the fMRI environment. Compared to controls, in CD patients the stress task elicited greater blood oxygen level dependent (BOLD) signals in the midcingulate cortex (MCC). The MCC integrate "high" emotional processes with afferent sensory information ascending from the gut. In light of these integrative functions, the stress-evoked MCC hyperactivity in CD patients might represent a plausible neural substrate for the association between stress and symptomatic disease. The MCC dysfunction might be involved in mechanisms of central disinhibition of nociceptive inputs leading to amplify the visceral sensitivity. Finally, the stress-evoked MCC hyperactivity might affect the regulation of intestinal motility resulting in exacerbation of disease symptoms and the autonomic and neuroendocrine regulation of inflammation resulting in enhanced inflammatory activity. © 2017 John Wiley & Sons Ltd.

Metabolic consequences of stress during childhood and adolescence.

Science.gov (United States)

Pervanidou, Panagiota; Chrousos, George P

2012-05-01

Stress, that is, the state of threatened or perceived as threatened homeostasis, is associated with activation of the stress system, mainly comprised by the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system normally functions in a circadian manner and interacts with other systems to regulate a variety of behavioral, endocrine, metabolic, immune, and cardiovascular functions. However, the experience of acute intense physical or emotional stress, as well as of chronic stress, may lead to the development of or may exacerbate several psychologic and somatic conditions, including anxiety disorders, depression, obesity, and the metabolic syndrome. In chronically stressed individuals, both behavioral and neuroendocrine mechanisms promote obesity and metabolic abnormalities: unhealthy lifestyles in conjunction with dysregulation of the stress system and increased secretion of cortisol, catecholamines, and interleukin-6, with concurrently elevated insulin concentrations, lead to development of central obesity, insulin resistance, and the metabolic syndrome. Fetal life, childhood, and adolescence are particularly vulnerable periods of life to the effects of intense acute or chronic stress. Similarly, these life stages are crucial for the later development of behavioral, metabolic, and immune abnormalities. Developing brain structures and functions related to stress regulation, such as the amygdala, the hippocampus, and the mesocorticolimbic system, are more vulnerable to the effects of stress compared with mature structures in adults. Moreover, chronic alterations in cortisol secretion in children may affect the timing of puberty, final stature, and body composition, as well as cause early-onset obesity, metabolic syndrome, and type 2 diabetes mellitus. The understanding of stress mechanisms leading to metabolic abnormalities in early life may lead to more effective prevention and intervention strategies of obesity

Child Behavior Problems, Teacher Executive Functions, and Teacher Stress in Head Start Classrooms.

Science.gov (United States)

Friedman-Krauss, Allison H; Raver, C Cybele; Neuspiel, Juliana M; Kinsel, John

2014-01-01

The current article explores the relationship between teachers' perceptions of child behavior problems and preschool teacher job stress, as well as the possibility that teachers' executive functions moderate this relationship. Data came from 69 preschool teachers in 31 early childhood classrooms in 4 Head Start centers and were collected using Web-based surveys and Web-based direct assessment tasks. Multilevel models revealed that higher levels of teachers' perceptions of child behavior problems were associated with higher levels of teacher job stress and that higher teacher executive function skills were related to lower job stress. However, findings did not yield evidence for teacher executive functions as a statistical moderator. Many early childhood teachers do not receive sufficient training for handling children's challenging behaviors. Child behavior problems increase a teacher's workload and consequently may contribute to feelings of stress. However, teachers' executive function abilities may enable them to use effective, cognitive-based behavior management and instructional strategies during interactions with students, which may reduce stress. Providing teachers with training on managing challenging behaviors and enhancing executive functions may reduce their stress and facilitate their use of effective classroom practices, which is important for children's school readiness skills and teachers' health.

Oxidative stress and lung function profiles of male smokers free from ...

African Journals Online (AJOL)

Oxidative stress and lung function profiles of male smokers free from COPD compared to those with COPD: A case-control study. ... However, conclusions about the role of blood or lung oxidative stress markers were disparate. Aims: To ... Keywords: inflammation; lung disease; spirometry; tobacco; sedentarily; stress oxidant ...

HPA axis hyperactivity and attempted suicide in young adult mood disorder inpatients.

Science.gov (United States)

Jokinen, Jussi; Nordström, Peter

2009-07-01

Hyperactivity of the Hypothalamic-Pituitary-Adrenal (HPA) axis is a consistent finding in Major Depressive Disorder (MDD) and most prospective studies of HPA-axis function have found that non-suppressors in the dexamethasone suppression test (DST) are more likely to commit suicide during follow-up. The results of studies on HPA-axis function and attempted suicide are less consistent. Suicide attempts are more common among young people than the elderly, whereas suicide is more common among the elderly. The impact of age related changes in HPA-axis system activity in relation to suicidal behaviour across the lifecycle may be of importance. The aim of the present study was to investigate the DST results in 36 young adult (30 years or younger) inpatients with mood disorder, with (n=18) and without suicide attempt at the index episode. The DST non-suppressor rate was 25% among young mood disorder inpatients. DST non-suppression was associated with suicide attempt and post-dexamethasone serum cortisol at 11:00 p.m. was significantly higher in suicide attempters compared to non-attempters. The DST non-suppressor rate was 39% in young adult suicide attempters compared with 11% in non-attempters. The results add to previous evidence in support of the role of HPA axis hyperactivity and suicidal behaviour. The present findings motivate to include HPA axis measures in the assessment of depression in young adults.

From the Bottom-Up: Chemotherapy and Gut-Brain Axis Dysregulation.

Science.gov (United States)

Bajic, Juliana E; Johnston, Ian N; Howarth, Gordon S; Hutchinson, Mark R

2018-01-01

The central nervous system and gastrointestinal tract form the primary targets of chemotherapy-induced toxicities. Symptoms associated with damage to these regions have been clinically termed chemotherapy-induced cognitive impairment and mucositis. Whilst extensive literature outlines the complex etiology of each pathology, to date neither chemotherapy-induced side-effect has considered the potential impact of one on the pathogenesis of the other disorder. This is surprising considering the close bidirectional relationship shared between each organ; the gut-brain axis. There are complex multiple pathways linking the gut to the brain and vice versa in both normal physiological function and disease. For instance, psychological and social factors influence motility and digestive function, symptom perception, and behaviors associated with illness and pathological outcomes. On the other hand, visceral pain affects central nociception pathways, mood and behavior. Recent interest highlights the influence of functional gut disorders, such as inflammatory bowel diseases and irritable bowel syndrome in the development of central comorbidities. Gut-brain axis dysfunction and microbiota dysbiosis have served as key portals in understanding the potential mechanisms associated with these functional gut disorders and their effects on cognition. In this review we will present the role gut-brain axis dysregulation plays in the chemotherapy setting, highlighting peripheral-to-central immune signaling mechanisms and their contribution to neuroimmunological changes associated with chemotherapy exposure. Here, we hypothesize that dysregulation of the gut-brain axis plays a major role in the intestinal, psychological and neurological complications following chemotherapy. We pay particular attention to evidence surrounding microbiota dysbiosis, the role of intestinal permeability, damage to nerves of the enteric and peripheral nervous systems and vagal and humoral mediated changes.

Differential sensitization of parenting on early adolescent cortisol: Moderation by profiles of maternal stress.

Science.gov (United States)

Martin, Christina Gamache; Kim, Hyoun K; Fisher, Philip A

2016-05-01

The hypothalamic-pituitary-adrenal (HPA) axis is a critical component of the body's stress-response neurobiological system, and its development and functioning are shaped by the social environment. Much of our understanding of the effects of the caregiving environment on the HPA axis is based on (a) parenting in young children and (b) individual maternal stressors, such as depression. Yet, less is known about how parenting behaviors and maternal stressors interact to influence child cortisol regulation, particularly in older children. With an ethnically diverse sample of 199 mothers and their early adolescent children (M=11.00years; 54% female), a profile analytic approach was used to investigate how multiple phenotypes of maternal stress co-occur and moderate the relation between parenting behaviors and youths' diurnal cortisol rhythms. Latent profile analysis yielded 4 profiles: current parenting stress, concurrent parenting and childhood stress, childhood stress, and low stress. For mothers with the concurrent parenting and childhood stress profile, inconsistent discipline, poor parental supervision, and harsh caregiving behaviors each were related to flattened diurnal cortisol rhythms in their adolescents. For mothers with the current parenting stress and childhood stress profiles, their use of inconsistent discipline was associated with flattened diurnal cortisol rhythms in their adolescents. For mothers with the low stress profile, none of the parenting behaviors was related to their adolescents' cortisol regulation. Findings suggest that based on mothers' stress profile, parenting behaviors are differentially related to youths' diurnal cortisol rhythms. Implications for parenting interventions are discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

Stress and obesity/metabolic syndrome in childhood and adolescence.

Science.gov (United States)

Pervanidou, Panagiota; Chrousos, George P

2011-09-01

Chronic distress contributes to the development of obesity and comorbid states. Stress is the disturbance of the complex dynamic equilibrium that all organisms must maintain, and is associated with activation of the Stress system comprising of the hypothalamic-pituitary-adrenal axis and the arousal/sympathetic nervous systems. The stress system functions in a baseline circadian fashion and interacts with other systems of the organism to regulate a variety of behavioral, endocrine, metabolic, immune and cardiovascular functions. The experience of perceived or real uncontrollable intense and/or chronic stress (distress) may lead to several psychopathologic conditions, including anxiety, depressive and psychosomatic disorders, substance abuse, obesity and the metabolic syndrome, and osteoporosis, as well as impaired reproductive and immune functions. Developing children and adolescents are particularly vulnerable to the effects of chronic stress. Both behavioral and biological pathways are involved in the connection between chronic stress and obesity in adults and children. Emotional "comfort" eating, lack of sleep, impulsive behaviours and selection of specific foods often characterize stressed individuals. In addition to specific behaviours, dysregulation of the stress system through increased secretion of cortisol and catecholamines, especially in the evening hours, and in concert with concurrently elevated insulin concentrations, leads to development of central obesity, insulin resistance and the metabolic syndrome. In children, chronic alterations in cortisol secretion may have additional effects on cognitive and emotional development, timing of puberty and final stature. Obese children and adolescents are frequently entangled in a vicious cycle between distress, impairing self-image and distorted self-image, maintaining and worsening distress.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

Science.gov (United States)

Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

2013-11-01

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (pBDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any

Cardiovascular Reactivity, Stress, and Physical Activity

Directory of Open Access Journals (Sweden)

Chun-Jung eHuang

2013-11-01

Full Text Available Psychological stress has been proposed as a major contributor to the progression of cardiovascular disease (CVD. Acute mental stress can activate the sympathetic-adrenal-medullary (SAM axis, eliciting the release of catecholamines (NE and EPI resulting in the elevation of heart rate (HR and blood pressure (BP. Combined stress (psychological and physical can exacerbate these cardiovascular responses, which may partially contribute to the elevated risk of CVD and increased proportionate mortality risks experienced by some occupations (e.g., firefighting and law enforcement. Studies have supported the benefits of physical activity on physiological and psychological health, including the cardiovascular response to acute stress. Aerobically trained individuals exhibit lower sympathetic nervous system (e.g., HR reactivity and enhanced cardiovascular efficiency (e.g., lower vascular reactivity and decreased recovery time in response to physical and/or psychological stress. In addition, resistance training has been demonstrated to attenuate cardiovascular responses and improve mental health. This review will examine stress-induced cardiovascular reactivity and plausible explanations for how exercise training and physical fitness (aerobic and resistance exercise can attenuate cardiovascular responses to stress. This enhanced functionality may facilitate a reduction in the incidence of stroke and myocardial infarction. Finally, this review will also address the interaction of obesity and physical activity on cardiovascular reactivity and CVD.

A Novel Shape-Free Plane Quadratic Polygonal Hybrid Stress-Function Element

Directory of Open Access Journals (Sweden)

Pei-Lei Zhou

2015-01-01

Full Text Available A novel plane quadratic shape-free hybrid stress-function (HS-F polygonal element is developed by employing the principle of minimum complementary energy and the fundamental analytical solutions of the Airy stress function. Without construction of displacement interpolation function, the formulations of the new model are much simpler than those of the displacement-based polygonal elements and can be degenerated into triangular or quadrilateral elements directly. In particular, it is quite insensitive to various mesh distortions and even can keep precision when element shape is concave. Furthermore, the element does not show any spurious zero energy modes. Numerical examples show the excellent performance of the new element, denoted by HSF-AP-19β, in both displacement and stress solutions.

Metabolic syndrome, activity of the hypothalamic-pituitary-adrenal axis and inflammatory mediators in depressive disorder.

Science.gov (United States)

Martinac, Marko; Pehar, Davor; Karlović, Dalibor; Babić, Dragan; Marcinko, Darko; Jakovljević, Miro

2014-03-01

Depression has been associated with various cardiovascular risk factors such as hypertension, obesity, atherogenic dyslipidemia and hyperglycemia. In depressive disorder, hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis and changes in the immune system have been observed. On the other hand, somatic diseases such as obesity, hyperlipidemia, hypertension and diabetes mellitus type 2 are now perceived as important comorbid conditions in patients with depression. The pathogenesis of the metabolic syndrome and depression is complex and poorly researched; however, it is considered that the interaction of chronic stress, psychotrauma, hypercotisolism and disturbed immune functions contribute to the development of these disorders. The aim of the study was to investigate the relationship between depression and metabolic syndrome regarding the HPA axis dysfunction and altered inflammatory processes. Literature search in Medline and other databases included articles written in English published between 1985 and 2012. Analysis of the literature was conducted using a systematic approach with the search terms such as depression, metabolic syndrome, inflammation, cytokines, glucocorticoids, cortisol, and HPA axis. In conclusion, the relationship between depression and metabolic syndrome is still a subject of controversy. Further prospective studies are required to clarify the possible causal relationship between depression and metabolic syndrome and its components. Furthermore, it is important to explore the possibility of a common biologic mechanism in the pathogenesis of these two disorders, in which special attention should be paid to the immune system function, especially the possible specific mechanisms by which cytokines can induce and maintain depressive symptoms and metabolic disorders. The data presented here emphasize the importance of recognition and treatment of depressive disorders with consequent reduction in the incidence of metabolic syndrome, but

Stress intensity factors and weight functions for cracks in front of notches

International Nuclear Information System (INIS)

Fett, T.

1993-12-01

The knowledge of stress intensity factors for cracks at notch roots is important for the fracture mechanical treatment of real components. Stress intensity factor solutions are available only for special notches and externally applied loads. For the treatment of more complex loadings as thermal stresses near the notch root the weight function is needed in addition. In the first part of this report weight functions for cracks in front of internal notches are derived from stress intensity factor solutions under external loading available in the literature. The second part deals with cracks in front of edge notches. Limit cases of stress intensity factors are derived which allow to estimate stress intensity factors for cracks in front of internal elliptical notches with arbitrary aspect ratio of the ellipse and for external notches. (orig.) [de

Effects of heat stress on baroreflex function in humans

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Crandall, Craig G.; Cui, Jian; Wilson, Thad E.

2003-01-01

INTRODUCTION: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function. METHODS: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non-pharmacological methods. In addition, the effects of heat stress on post-synaptic vasoconstrictor responsiveness were assessed. RESULTS: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists. CONCLUSION: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.

Prenatal stress programs neuroendocrine stress responses and affective behaviors in second generation rats in a sex-dependent manner.

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Grundwald, Natalia J; Brunton, Paula J

2015-12-01

An adverse environment in early life is often associated with dysregulation of the hypothalamo-pituitary-adrenal (HPA) axis and higher rates of mood disorders in adulthood. In rats, exposure to social stress during pregnancy results in hyperactive HPA axis responses to stress in the adult offspring and heightened anxiety behavior in the males, but not the females. Here we tested whether, without further intervention, the effects of prenatal stress (PNS) in the first filial generation (F1) are transmitted to the F2 generation via the maternal line. F1 control and PNS female rats were mated with control males and housed under non-stress conditions throughout pregnancy. HPA axis responses to acute stress, anxiety- and depressive-like behavior were assessed in the adult F2 offspring. ACTH and corticosterone responses to an acute stressor were markedly enhanced in F2 PNS females compared with controls. This was associated with greater corticotropin releasing hormone (Crh) mRNA expression in the paraventricular nucleus and reduced hippocampal glucocorticoid (Gr) and mineralocorticoid receptor (Mr) mRNA expression. Conversely, in the F2 PNS males, HPA axis responses to acute stress were attenuated and hippocampal Gr mRNA expression was greater compared with controls. F2 PNS males exhibited heightened anxiety-like behavior (light-dark box and elevated plus maze) compared with F2 control males. Anxiety-like behavior did not differ between F2 control and PNS females during metestrus/diestrus, however at proestrus/estrus, F2 control females displayed a reduction in anxiety-like behavior, but this effect was not observed in the F2 PNS females. Heightened anxiety in the F2 PNS males was associated with greater Crh mRNA expression in the central nucleus of the amygdala compared with controls. Moreover, Crh receptor-1 (Crhr1) mRNA expression was significantly increased, whereas Crhr2 mRNA was significantly decreased in discrete regions of the amygdala in F2 PNS males compared

Locus of Control Predicts Cortisol Reactivity and Speech Performance in Response to Acute Stress in Undergraduate Students

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Szabo, Yvette Z.; Chang, Andrew; Chancellor-Freeland, Cheryl

2015-01-01

Previous studies have found that an individual's perception of control in a situation (Locus of Control; LOC) can serve as a protective factor that has physiological and psychological benefits. The present study examines LOC in an acute stress paradigm to examine the relationship between LOC and hypothalamic-pituitary-adrenal axis functioning as…

The Place of Stress and Emotions in the Irritable Bowel Syndrome.

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Pellissier, S; Bonaz, B

2017-01-01

Our emotional state can have many consequences on our somatic health and well-being. Negative emotions such as anxiety play a major role in gut functioning due to the bidirectional communications between gut and brain, namely, the brain-gut axis. The irritable bowel syndrome (IBS), characterized by an unusual visceral hypersensitivity, is the most common disorder encountered by gastroenterologists. Among the main symptoms, the presence of current or recurrent abdominal pain or discomfort associated with bloating and altered bowel habits characterizes this syndrome that could strongly alter the quality of life. This chapter will present the physiopathology of IBS and explain how stress influences gastrointestinal functions (permeability, motility, microbiota, sensitivity, secretion) and how it could be predominantly involved in IBS. This chapter will also describe the role of the autonomic nervous system and the hypothalamic-pituitary axis through vagal tone and cortisol homeostasis. An analysis is made about how emotions and feelings are involved in the disruption of homeostasis, and we will see to what extent the balance between vagal tone and cortisol may reflect dysfunctions of the brain-gut homeostasis. Finally, the interest of therapeutic treatments focused on stress reduction and vagal tone enforcement is discussed. © 2017 Elsevier Inc. All rights reserved.

Child Behavior Problems, Teacher Executive Functions, and Teacher Stress in Head Start Classrooms

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Friedman-Krauss, Allison H.; Raver, C. Cybele; Neuspiel, Juliana M.; Kinsel, John

2017-01-01

Research Findings The current article explores the relationship between teachers’ perceptions of child behavior problems and preschool teacher job stress, as well as the possibility that teachers’ executive functions moderate this relationship. Data came from 69 preschool teachers in 31 early childhood classrooms in 4 Head Start centers and were collected using Web-based surveys and Web-based direct assessment tasks. Multilevel models revealed that higher levels of teachers’ perceptions of child behavior problems were associated with higher levels of teacher job stress and that higher teacher executive function skills were related to lower job stress. However, findings did not yield evidence for teacher executive functions as a statistical moderator. Practice or Policy Many early childhood teachers do not receive sufficient training for handling children’s challenging behaviors. Child behavior problems increase a teacher’s workload and consequently may contribute to feelings of stress. However, teachers’ executive function abilities may enable them to use effective, cognitive-based behavior management and instructional strategies during interactions with students, which may reduce stress. Providing teachers with training on managing challenging behaviors and enhancing executive functions may reduce their stress and facilitate their use of effective classroom practices, which is important for children’s school readiness skills and teachers’ health. PMID:28596698

The Trading Axis in Irkutsk Downtown

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Elena Grigoryeva

2016-10-01

Full Text Available The article reveals a linear concentration of the trading function in the historical center of Irkutsk. It features historical prerequisites and continuation of the tradition in the post-Soviet period, given the conversion of plants and factories. The article analyses the current state and prospects of modernization of the trading axis with its transformation into a modern public space.

Linear and non-linear dose-response functions reveal a hormetic relationship between stress and learning.

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Zoladz, Phillip R; Diamond, David M

2008-10-16

Over a century of behavioral research has shown that stress can enhance or impair learning and memory. In the present review, we have explored the complex effects of stress on cognition and propose that they are characterized by linear and non-linear dose-response functions, which together reveal a hormetic relationship between stress and learning. We suggest that stress initially enhances hippocampal function, resulting from amygdala-induced excitation of hippocampal synaptic plasticity, as well as the excitatory effects of several neuromodulators, including corticosteroids, norepinephrine, corticotropin-releasing hormone, acetylcholine and dopamine. We propose that this rapid activation of the amygdala-hippocampus brain memory system results in a linear dose-response relation between emotional strength and memory formation. More prolonged stress, however, leads to an inhibition of hippocampal function, which can be attributed to compensatory cellular responses that protect hippocampal neurons from excitotoxicity. This inhibition of hippocampal functioning in response to prolonged stress is potentially relevant to the well-described curvilinear dose-response relationship between arousal and memory. Our emphasis on the temporal features of stress-brain interactions addresses how stress can activate, as well as impair, hippocampal functioning to produce a hormetic relationship between stress and learning.

Family functioning, parenting stress and quality of life in mothers and fathers of Polish children with high functioning autism or Asperger syndrome.

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Pisula, Ewa; Porębowicz-Dörsmann, Anna

2017-01-01

The aim of the study was to investigate the perception of the family functioning in parents of children with autism spectrum disorders (ASD) with normal-range intelligence and the relationships between family functioning, parenting stress and quality of life. Dyads of parents of children with ASD without intellectual disability and parents of typically developing children (controls) completed a set of self-report questionnaires. Parents of children with ASD reported lower functioning of the family as a whole and their own functioning as family members; they exhibited higher levels of parenting stress and lower quality of life. Mothers of children with ASD experienced more stress in personal domain than fathers. Relationships between family functioning, parenting stress and quality of life have been established. There were also moderate to strong correlations in mother-father dyads between their assessments of family functioning, parenting stress and QoL in social relationships and environmental domains.

Dynamic regulation of NMDAR function in the adult brain by the stress hormone corticosterone

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Yiu Chung eTse

2012-03-01

Full Text Available Stress and corticosteroids dynamically modulate the expression of synaptic plasticity at glutamatergic synapses in the developed brain. Together with alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid receptors (AMPAR, N-methyl-D-aspartate receptors (NMDAR are critical mediators of synaptic function and are essential for the induction of many forms of synaptic plasticity. Regulation of NMDAR function by cortisol/corticosterone (CORT may be fundamental to the effects of stress on synaptic plasticity. Recent reports of the efficacy of NMDAR antagonists in treating certain stress-associated psychopathologies further highlight the importance of understanding the regulation of NMDAR function by CORT. Knowledge of how corticosteroids regulate NMDAR function within the adult brain is relatively sparse, perhaps due to a common belief that NMDAR function is relatively stable in the adult brain. We review recent results from our laboratory and others demonstrating dynamic regulation of NMDAR function by CORT in the adult brain. In addition, we consider the issue of how differences in the early life environment may program differential sensitivity to modulation of NMDAR function by CORT and how this may influence synaptic function during stress. Findings from these studies demonstrate that NMDAR function in the adult hippocampus remains sensitive to even brief exposures to CORT and that the capacity for modulation of NMDAR may be programmed, in part, by the early life environment. Modulation of NMDAR function may contribute to dynamic regulation of synaptic plasticity and adaptation in the face of stress, however enhanced NMDAR function may be implicated in mechanisms of stress related psychopathologies including depression.