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Objective: Primary polydipsia is characterized by excessive fluid intake which may suppress vasopressin levels. It is speculated that suppressed vasopressin levels lead to a dysregulated hypothalamic–pituitary–adrenal (HPA) axis as vasopressin co‐modulates the HPA axis. However, data are contradictory. The aim of this study was to investigate markers of the HPA axis in patients with primary polydipsia compared to healthy controls. Design: Exploratory analysis combining data from two different prospective observational studies. Patients: We included 34 patients with primary polydipsia (68% females, median aged 29.5 years (interquartile range, IQR: 26.0, 38.8) and 20 healthy controls (55% females, median age 24.0 years [IQR: 22.0, 27.2]). Measurements: The main outcome was difference in HPA axis activity assessed using circadian serum and salivary cortisol, 24‐h urinary free cortisol and cortisol levels before and after adrenocorticotropic hormone (ACTH) stimulation; vasopressin suppression was assessed measuring fasting copeptin levels between patients with primary polydipsia and healthy controls using Wilcoxon rank‐sum test. Results: No difference was seen in circadian serum cortisol levels (p =.9), urinary free cortisol levels (p =.17) and serum cortisol in response to ACTH stimulation (p =.77) between groups. Circadian salivary cortisol levels were significantly lower in patients with primary polydipsia compared to healthy controls with an estimated difference of −3.7 nmol/L (95% CI: −5.5, −1.8 nmol/L, p <.001). Fasting copeptin levels were significantly lower in patients with primary polydipsia compared to healthy volunteers (p < 0.01). Conclusion: Our results suggest no difference in HPA axis activity between patients with primary polydipsia and healthy controls. The observed difference in salivary cortisol levels may be linked to a dilution effect in saliva rather than an altered stress axis considering the other findings. [ABSTRACT FROM AUTHOR]

BackgroundWe have recently shown that binge or heavy levels of alcohol drinking increase deoxyribonucleic acid (DNA) methylation and reduce gene expression of proopiomelanocortin (POMC) and period 2 (PER2) in adult human subjects (Gangisetty et al., Alcohol Clin Exp Res, 43, 2019, 212). One hypothesis would be that methylation of these 2 genes is consistently associated with alcohol exposure and could be used as biomarkers to predict risk of prenatal alcohol exposure (PAE). Results of the present study provided some support for this hypothesis.MethodsWe conducted a series of studies to determine DNA methylation changes in stress regulatory genes proopiomelanocortin (POMC) and period 2 (PER2) using biological samples from 3 separate cohorts of patients: (i) pregnant women who consumed moderate-to-high levels of alcohol or low/unexposed controls, (ii) children with PAE and non-alcohol-exposed controls, and (iii) children with PAE treated with or without choline.ResultsWe found pregnant women who consumed moderate-to-high levels of alcohol and gave birth to PAE children had higher DNA methylation of POMC and PER2. PAE children also had increased methylation of POMC and PER2. The differences in the gene methylation of PER2 and POMC between PAE and controls did not differ by maternal smoking status. PAE children had increased levels of stress hormone cortisol and adrenocorticotropic hormone. Choline supplementation reduced DNA hypermethylation and increased expression of POMC and PER2 in children with PAE.ConclusionsThese data suggest that PAE significantly elevates DNA methylation of POMC and PER2 and increases levels of stress hormones. Furthermore, these results suggest the possibility that measuring DNA methylation levels of PER2 and POMC in biological samples from pregnant women or from children may be useful for identification of a woman or a child with PAE.

Stress generally indicates any change of an exogenous or endogenous nature that can exert negative effects on the individual. While some recent studies showed that acute stress might actually be beneficial for the cognitive functions, chronic stress was found to be implicated in neuropsychiatric, cardiovascular, digestive, metabolic, endocrine, and malignant disorders development. Moreover, it was recently suggested that chronic stress exposure in animal models could successfully induce behavioural and molecular impairments described in the aforementioned disorders. Zebrafish (Danio rerio) models are nowadays gaining more attention due to their advantages, as well as their complete neurobehavioral, biochemical, and genetic description, great similarity to human. In this context, the aim of this mini review is to describe and to identify possible interdisciplinary applications of the neurobehavioral and biochemical changes induced by chronic stress exposure in zebrafish. [ABSTRACT FROM AUTHOR]

Chronic stress has long been hypothesized to play a role in driving population cycles. Christian (1950) hypothesized that high population density results in chronic stress and mass "die-offs" in small mammal populations. Updated variations of this hypothesis propose that chronic stress at high population density may reduce fitness, reproduction, or program aspects of phenotype, driving population declines. We tested the effect of density on the stress axis in meadow voles (Microtus pennsylvanicus) by manipulating population density in field enclosures over three years. Using fecal corticosterone metabolites as a non-invasive measure of glucocorticoid (GC) concentrations, we found that density alone was not associated with GC differences. However, we found that the seasonal relationship of GC levels differed by density treatment, with high-density populations having elevated GC levels early in the breeding season and decreasing towards late summer. We additionally tested hippocampal glucocorticoid receptor and mineralocorticoid receptor gene expression in juvenile voles born at different densities, with the hypothesis that high density may reduce receptor expression, altering negative feedback of the stress axis. We found that females had marginally higher glucocorticoid receptor expression at high density, no effect in males, and no detectable effect of density on mineralocorticoid receptor expression in either sex. Hence, we found no evidence that high density directly impairs negative feedback in the hippocampus, but rather female offspring may be better equipped for negative feedback. We compare our findings with prior studies to attempt to disentangle the complicated relationship between density, seasonality, sex, reproduction and the stress axis. [ABSTRACT FROM AUTHOR]

We conducted a systematic review with meta‐analytic elements using publicly available Gene Expression Omnibus (GEO) datasets to determine the role of epigenetic mechanisms in prenatal alcohol exposure (PAE)‐induced hypothalamic–pituitary–adrenal (HPA) axis dysfunctions in offspring. Several studies have demonstrated that PAE has long‐term consequences on HPA axis functions in offspring. Some studies determined that alcohol‐induced epigenetic alterations during fetal development persist in adulthood. However, additional research is needed to understand the major epigenetic events leading to alcohol‐induced teratogenesis of the HPA axis. Our network analysis of GEO datasets identified key pathways relevant to alcohol‐mediated histone modifications, DNA methylation, and miRNA involvement associated with PAE‐induced alterations of the HPA axis. Our analysis indicated that PAE perturbated the epigenetic machinery to activate corticotrophin‐releasing hormone, while it suppressed opioid, glucocorticoid receptor, and circadian clock genes. These results help to further our understanding of the epigenetic basis of alcohol's effects on HPA axis development. [ABSTRACT FROM AUTHOR]

The importance of steroidogenesis is underscored by its vital and conserved functions from higher to lower vertebrate species, such as stress, immune and inflammatory responses, sexual development and reproduction, osmoregulation and even the ability to adapt to the environment and environmental changes. Correspondingly, the rate-limiting step of steroidogenesis mediated by the steroidogenic acute regulatory protein is an ongoing target for scientific investigation. An expanding collection of studies has now reported key similarities, as well as some differences, in the transcriptional and translational regulation of steroidogenic acute regulatory protein across species. This review will discuss the current understanding of steroidogenic acute regulatory protein in fish, as these lower vertebrate models uniquely rely on steroid hormones for osmotic balance, reproductive functions, responses to environmental stimuli and much more.

Abstract Developmental plasticity can allow the exploitation of alternative diets. While such flexibility during early life is often adaptive, it can leave a legacy in later life that alters the overall health and fitness of an individual. Species of the spadefoot toad genus Spea are uniquely poised to address such carryover effects because their larvae can consume drastically different diets: their ancestral diet of detritus or a derived shrimp diet. Here, we use Spea bombifrons to assess the effects of developmental plasticity in response to larval diet type and nutritional stress on juvenile behaviors and stress axis reactivity. We find that, in an open‐field assay, juveniles fed shrimp as larvae have longer latencies to move, avoid prey items more often, and have poorer prey‐capture abilities. While juveniles fed shrimp as larvae are more exploratory, this effect disappears if they also experienced a temporary nutritional stressor during early life. The larval shrimp diet additionally impairs juvenile jumping performance. Finally, larvae that were fed shrimp under normal nutritional conditions produce juveniles with higher overall glucocorticoid levels, and larvae that were fed shrimp and experienced a temporary nutritional stressor produce juveniles with higher stress‐induced glucocorticoid levels. Thus, while it has been demonstrated that consuming the novel, alternative diet can be adaptive for larvae in nature, doing so has marked effects on juvenile phenotypes that may recalibrate an individual's overall fitness. Given that organisms often utilize diverse diets in nature, our study underscores the importance of considering how diet type interacts with early‐life nutritional adversity to influence subsequent life stages.

Anticipation of stress induces physiological, behavioral and cognitive adjustments that are required for an appropriate response to the upcoming situation. Additional research examining the response of cardiopulmonary parameters and stress hormones during anticipation of stress in different chronic stress adaptive models is needed. As an addition to our previous research, a total of 57 subjects (16 elite male wrestlers, 21 water polo player and 20 sedentary subjects matched for age) were analyzed. Cardiopulmonary exercise testing (CPET) on a treadmill was used as the laboratory stress model; peak oxygen consumption (VO2) was obtained during CPET. Plasma levels of adrenocorticotropic hormone (ACTH), cortisol, alpha-melanocyte stimulating hormone (alpha-MSH) and N-terminal-pro-B type natriuretic peptide (NT-pro-BNP) were measured by radioimmunometric, radioimmunoassay and immunoassay sandwich technique, respectively, together with cardiopulmonary measurements, 10 minutes pre-CPET and at the initiation of CPET. The response of diastolic blood pressure and heart rate was different between groups during stress anticipation (p=0.019, 0.049, respectively), while systolic blood pressure, peak VO2 and carbon-dioxide production responses were similar. ACTH and cortisol increased during the experimental condition, NT-pro-BNP decreased and alpha-MSH remained unchanged. All groups had similar hormonal responses during stress anticipation with the exception of the ACTH/cortisol ratio. In all three groups, DNT-pro-BNP during stress anticipation was the best independent predictor of peak VO2 (B=36.01, r=0.37, p=0.001). In conclusion, the type of chronic stress exposure influences the hemodynamic response during anticipation of physical stress and the path of hormonal stress axis activation. Stress hormones released during stress anticipation may hold predictive value for overall cardiopulmonary performance during the stress condition. [ABSTRACT FROM AUTHOR]

Stress response is essential for the organism to quickly restore physiological homeostasis disturbed by various environmental insults. In addition to well-established physiological cascades, stress also evokes various brain and behavioral responses. Aquatic animal models, including the zebrafish (Danio rerio), have been extensively used to probe pathobiological mechanisms of stress and stress-related brain disorders. Here, we critically discuss the use of zebrafish models for studying mechanisms of stress and modeling its disorders experimentally, with a particular cross-taxon focus on the potential evolution of stress responses from zebrafish to rodents and humans, as well as its translational implications.

Developmental plasticity can allow the exploitation of alternative diets. While such flexibility during early life is often adaptive, it can leave a legacy in later life that alters the overall health and fitness of an individual. Species of the spadefoot toad genus Spea are uniquely poised to address such carryover effects because their larvae can consume drastically different diets: their ancestral diet of detritus or a derived shrimp diet. Here, we use Speabombifrons to assess the effects of developmental plasticity in response to larval diet type and nutritional stress on juvenile behaviors and stress axis reactivity. We find that, in an open‐field assay, juveniles fed shrimp as larvae have longer latencies to move, avoid prey items more often, and have poorer prey‐capture abilities. While juveniles fed shrimp as larvae are more exploratory, this effect disappears if they also experienced a temporary nutritional stressor during early life. The larval shrimp diet additionally impairs juvenile jumping performance. Finally, larvae that were fed shrimp under normal nutritional conditions produce juveniles with higher overall glucocorticoid levels, and larvae that were fed shrimp and experienced a temporary nutritional stressor produce juveniles with higher stress‐induced glucocorticoid levels. Thus, while it has been demonstrated that consuming the novel, alternative diet can be adaptive for larvae in nature, doing so has marked effects on juvenile phenotypes that may recalibrate an individual's overall fitness. Given that organisms often utilize diverse diets in nature, our study underscores the importance of considering how diet type interacts with early‐life nutritional adversity to influence subsequent life stages. [ABSTRACT FROM AUTHOR]

Small everyday gestures such as a tap on the shoulder can affect the way humans feel and act. Touch can have a calming effect and alter the way stress is handled, thereby promoting mental and physical health. Due to current technical advances and the growing role of intelligent robots in households and healthcare, recent research also addressed the potential of robotic touch for stress reduction. In addition, touch by non-human agents such as animals or inanimate objects may have a calming effect. This conceptual article will review a selection of the most relevant studies reporting the physiological, hormonal, neural, and subjective effects of touch on stress, arousal, and negative affect. Robotic systems capable of non-social touch will be assessed together with control strategies and sensor technologies. Parallels and differences of human-to-human touch and human-to-non-human touch will be discussed. We propose that, under appropriate conditions, touch can act as (social) signal for safety, even when the interaction partner is an animal or a machine. We will also outline potential directions for future research and clinical relevance. Thereby, this review can provide a foundation for further investigations into the beneficial contribution of touch by different agents to regulate negative affect and arousal in humans.

Environmental sex determination (ESD) is common among ectothermic vertebrates. The stress axis and production of stress hormones (corticosteroids) regulates ESD in fish, but evidence of a similar influence in reptiles is sparse and conflicting. The central bearded dragon (Pogona vitticeps) has a system of sex determination involving the interplay between sex chromosomes (ZZ/ZW female heterogamety) and the thermal environment. High egg incubation temperatures induce sex reversal of the ZZ genotype, feminizing chromosomally male individuals. Here we show that corticosterone elevation is not associated with sex reversal in the central bearded dragon, either during embryonic development or adulthood. We also demonstrate experimentally that sex determination is not affected by corticosterone injection into the yolk. This strongly suggests that stress axis upregulation by high temperature during incubation does not cause sex reversal in P. vitticeps. Our work is in general agreement with other research in reptiles, which suggests that the stress axis does not mediate sex in reptiles with ESD. Alternative biological systems may be responsible for capturing environmental conditions during reptile development, such as cellular calcium and redox regulation or the action of temperature‐sensitive splicing factors. Research Highlights: Yolk injection of corticosterone early in development does not induce sex reversal in the central bearded dragon (Pogona vitticeps).Before the differentiation of the gonad, tissue corticosterone levels are not elevated in embryos incubated at high sex‐reversing temperatures.Sex‐reversed females do not display upregulation of basal levels of plasma corticosterone or oxidized guanine (as an indicator of DNA damage). [ABSTRACT FROM AUTHOR]

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Small everyday gestures such as a tap on the shoulder can affect the way humans feel and act. Touch can have a calming effect and alter the way stress is handled, thereby promoting mental and physical health. Due to current technical advances and the growing role of intelligent robots in households and healthcare, recent research also addressed the potential of robotic touch for stress reduction. In addition, touch by non-human agents such as animals or inanimate objects may have a calming effect. This conceptual article will review a selection of the most relevant studies reporting the physiological, hormonal, neural, and subjective effects of touch on stress, arousal, and negative affect. Robotic systems capable of non-social touch will be assessed together with control strategies and sensor technologies. Parallels and differences of human-to-human touch and human-to-non-human touch will be discussed. We propose that, under appropriate conditions, touch can act as (social) signal for safety, even when the interaction partner is an animal or a machine. We will also outline potential directions for future research and clinical relevance. Thereby, this review can provide a foundation for further investigations into the beneficial contribution of touch by different agents to regulate negative affect and arousal in humans. [ABSTRACT FROM AUTHOR]

Arctic ecosystems are changing rapidly in response to climate warming. While Arctic mammals are highly evolved to these extreme environments, particularly with respect to their stress axis, some species may have limited capacity to adapt to this change. We examined changes in key components of the stress axis (cortisol and its carrier protein—corticosteroid binding globulin [CBG]) in polar bears (Ursus maritimus) from western Hudson Bay (N = 300) over a 33 year period (1983–2015) during which time the ice‐free period was increasing. Changing sea ice phenology limits spring hunting opportunities and extends the period of onshore fasting. We assessed the response of polar bears to a standardized stressor (helicopter pursuit, darting, and immobilization) during their onshore fasting period (late summer–autumn) and quantified the serum levels of the maximum corticosteroid binding capacity (MCBC) of CBG, the serum protein that binds cortisol strongly, and free cortisol (FC). We quantified bear condition (age, sex, female with cubs or not, fat condition), sea ice (breakup in spring–summer, 1 year lagged freeze‐up in autumn), and duration of fasting until sample collection as well as cumulative impacts of the latter environmental traits from the previous year. Data were separated into "good" years (1983–1990) when conditions were thought to be optimal and "poor" years (1991–2015) when sea ice conditions deteriorated and fasting on land was extended. MCBC explained 39.4% of the variation in the good years, but only 28.1% in the poor ones, using both biological and environmental variables. MCBC levels decreased with age. Changes in FC were complex, but more poorly explained. Counterintuitively, MCBC levels increased with increased time onshore, 1 year lag effects, and in poor ice years. We conclude that MCBC is a biomarker of stress in polar bears and that the changes we document are a consequence of climate warming. [ABSTRACT FROM AUTHOR]

Many strains of zebrafish (Danio rerio) are readily available. Earlier we observed differences between AB and Tupfel long-fin (TL) larvae regarding baseline hypothalamus-pituitary-interrenal (HPI) axis activity and (neuro)development. Light regimes, i.e. 14 h light:10 h dark and 24 h continuous dark or light, affect hatching rate and larval growth. Here, we assessed baseline transcript abundance of HPI-axis-related genes and (neuro)development-related genes of AB and TL larvae (5 days post fertilisation) using these light regimes. A principal component analysis revealed that in AB larvae the baseline expression of HPI-axis-related genes was higher the more hours of light, while the expression of (neuro)development-related genes was higher under 14 h light:10 h dark than under both continuous light or dark. In TL larvae, a complex pattern emerged regarding baseline expression of HPI-axis-related and (neuro)development-related genes. These data extend data of earlier studies by showing that light regimes affect gene-expression in larvae, and more importantly so, strengthen the notion of differences between larvae of the AB and TL strain. The latter finding adds to the growing database of phenotypical differences between zebrafish of the AB and TL strain.

Noradrenergic pathways have been implicated in eating pathologies. These experiments sought to examine how dietary-induced binge eating influences the neuronal activity of the locus coeruleus (LC)-norepinephrine (NE) system. Young adult female Sprague Dawley rats (7–8 weeks old) were exposed to a repeated intermittent (twice weekly) cycle of 30-min access to a highly palatable sweetened fat (i.e., vegetable shortening with 10% sucrose) with or without intermittent (24 h) calorie restriction (Restrict Binge or Binge groups, respectively). Age- and weight-matched female control rats were exposed to standard chow feeding (Naive group) or intermittent chow feeding (Restrict group). The Binge and Restrict Binge groups demonstrated an escalation in sweet-fat food intake after 2.5 weeks. On week 3, in vivo single-unit LC electrophysiological activity was recorded under isoflurane anesthesia. Restrict Binge (20 cells from six rats) and Binge (27 cells from six rats) had significantly reduced (approximate 20% and 26%, respectively) evoked LC discharge rates compared with naive rats (22 cells, seven rats). Spontaneous and tonic discharge rates were not different among the groups. Signal-to-noise ratio was reduced in the groups with intermittent sweetened fat exposure. In order to investigate the neuropeptide alterations as a consequence of dietary binge eating, relative gene expression of neuropeptide Y (NPY), glucagon-like peptide 1 receptor (GLP-1r), prodynorphin, and related genes were measured in LC and hypothalamic arcuate (Arc) regions. Glp-1r, Npy2r, and Pdyn in LC region were reduced with repeated intermittent restriction. Npy1r was reduced by approximately 27% in ARC of Restrict compared with Naive group. Such data indicate that dietary-induced binge eating alters the neural response of LC neurons to sensory stimuli and dampens the neural stress response.

The social environment encountered early during development can temporarily or permanently influence life history decisions and behaviour of individuals and correspondingly shape molecular pathways. In the highly social cichlid fish Neolamprologus pulcher, deprivation of brood care permanently affects social behaviour and alters the expression of stress axis genes in juveniles and adults. It is unclear when gene expression patterns change during early life depending on social experience, and which genes are involved. We compared brain gene expression of N. pulcher at two time points during the social experience phase when juveniles were reared either with or without brood care, and one time point shortly afterwards. We compared (a) whole transcriptomes and (b) expression of 79 genes related to stress regulation, in order to define a neurogenomic state of stress for each fish. At developmental day 75, that is, after the social experience phase, 43 genes were down‐regulated in fish having experienced social deprivation, while two genes involved in learning and memory and in post‐translational modifications of proteins (PTM), respectively, were up‐regulated. Down‐regulated genes were mainly associated with immunity, PTM and brain function. In contrast, during the experience phase no genes were differentially expressed when assessing the whole transcriptome. When focusing on the neurogenomic state associated with the stress response, we found that individuals from the two social treatments differed in how their brain gene expression profiles changed over developmental stages. Our results indicate that the early social environment influences the transcriptional activation in fish brains, both during and after an early social experience, possibly affecting plasticity, immune system function and stress axis regulation. [ABSTRACT FROM AUTHOR]

Snowshoe hares, Lepus americanus , are the dominant prey species in the boreal forest and they undergo regular, predator-driven population cycles every 8–11 years. Previous research has found that hare stress physiology is highly sensitive to both within-year (seasonal/litter group) and across-year (cycle phase) variation in predation risk and that maternal–offspring stress profiles are tightly correlated. Thus, both pre- and postnatal environments may interact to shape offspring physiological phenotype. If changes in the function and reactivity of the maternal stress axis are associated with variation in offspring behaviours that increase survival during periods of high predation risk, then the maternal effects on offspring physiology seen previously could represent a mechanistic route of adaptive maternal programming. To examine the relationship between physiology and behaviour in snowshoe hares, we monitored free-ranging adult and juvenile stress hormone levels in the first and second litters of the breeding season and assessed open field exploratory behaviour in weaning-age and independent juveniles in the southwestern Yukon (Canada) during 2013–2015, when predator density was low but increasing. Thus, our study spanned the late low phase (2013) and the early increase phase (2014–2015) of the hare population cycle. We found that increased concentrations of faecal cortisol metabolites (FCMs) were associated with aspects of risk avoidance in weaning-age hares. Juveniles with higher stress hormone levels spent more time under cover and were less active during open field trials, highlighting a potential mechanistic route to allow individuals to sensitively cope with a changing environment. Although average FCM levels of breeding females and juveniles were not correlated with one another and litter-based differences in physiology and behaviour were not present during these low-risk phases of the cycle, the association between stress hormone levels and behaviour sets the stage for adaptive maternal effects on offspring behaviour and survival as the cycle progresses and predation risk intensifies. • Wild snowshoe hares are acutely sensitive to fluctuating predation risk. • We measured population-level stress and juvenile open field exploratory behaviour. • High faecal cortisol levels were associated with risk avoidance in juveniles. • Pre- and postnatal environments influenced offspring physiological phenotype. [ABSTRACT FROM AUTHOR]

Noradrenergic pathways have been implicated in eating pathologies. These experiments sought to examine how dietary-induced binge eating influences the neuronal activity of the locus coeruleus (LC)-norepinephrine (NE) system. Young adult female Sprague Dawley rats (7–8 weeks old) were exposed to a repeated intermittent (twice weekly) cycle of 30-min access to a highly palatable sweetened fat (i.e., vegetable shortening with 10% sucrose) with or without intermittent (24 h) calorie restriction (Restrict Binge or Binge groups, respectively). Age- and weight-matched female control rats were exposed to standard chow feeding (Naive group) or intermittent chow feeding (Restrict group). The Binge and Restrict Binge groups demonstrated an escalation in sweet-fat food intake after 2.5 weeks. On week 3, in vivo single-unit LC electrophysiological activity was recorded under isoflurane anesthesia. Restrict Binge (20 cells from six rats) and Binge (27 cells from six rats) had significantly reduced (approximate 20% and 26%, respectively) evoked LC discharge rates compared with naive rats (22 cells, seven rats). Spontaneous and tonic discharge rates were not different among the groups. Signal-to-noise ratio was reduced in the groups with intermittent sweetened fat exposure. In order to investigate the neuropeptide alterations as a consequence of dietary binge eating, relative gene expression of neuropeptide Y (NPY), glucagon-like peptide 1 receptor (GLP-1r), prodynorphin, and related genes were measured in LC and hypothalamic arcuate (Arc) regions. Glp-1r , Npy2r , and Pdyn in LC region were reduced with repeated intermittent restriction. Npy1r was reduced by approximately 27% in ARC of Restrict compared with Naive group. Such data indicate that dietary-induced binge eating alters the neural response of LC neurons to sensory stimuli and dampens the neural stress response. [ABSTRACT FROM AUTHOR]

Structural-paragenetic and kinematic methods of tectonophysics are applied to study earthquake focal mechanisms of the Zagros system. Nodal planes of focal mechanisms are identified as L-, L′- and R-, R′-shears by the first method, whereby coordinates of principal stress axes P, T and N (i.e. in tectonophysics, σ1, σ3 and σ2, if σ1 ≥ σ2 ≥ σ3) are defined. ‘Working’ nodal planes corresponding to activated ruptures are revealed. Axes of the main normal stresses are combined into local groups on the basis of the kinematic identity of planes of seismogenic ruptures (Figure 2). The second method is applied to construct stereograms of the main axes P, T and N, to construct and interpret stereograms of vectors of seismogenic shifts (Figure 3), and to more clearly define coordinates of principal axes σ1, σ3 и σ2. As evidenced by their comparison, coordinates of the principal axes obtained by the two tectonophysical methods are well coincident (see Figure 2). Five groups of seismogenesis are distinguished; they differ in combination of deformation regimes and kinematic conditions. Locations are determined of the areas wherein earthquake foci of similar parameters are located. This means that seismogenic zones are distinguished; structural and kinematic characteristics of such zones are determined by parameters of stereographic models of corresponding types of seismogenesis (Figures 4 and 5). It is established that the region is dominated by shear and upthrust deformation regimes due to regional submeridional compression and SW-NE compression (see Figures 4 and 5). Submeridional subhorizontal compression is explained by the northward movement of the Arabian plate, and SW-NE compression is explained by divergent processes within the limits of the Red Sea rift. The time pattern of the seismogenic processes from 1979 to 2001 shows that submeridional compression and SW-NE compression are associated with different deep mechanisms. Processes of SE-NW compression, which are observed in the northern part of the Arabian plate, are caused by its interaction with the Eastern Black Sea microplate.

Highlights • Type 1 diabetes causes an increase in NE release in the PVN and serum corticosterone levels. • The brain of diabetic animals is less sensitive to leptin compared to the adrenal gland. • Clonidine blocked the effect of leptin in the PVN and adrenal, but Isoproterenol blocked the effect on the adrenal gland. Abstract Type I Diabetes (T1D) is associated with reduced leptin levels and increased stress axis activity marked by elevations in norepinephrine (NE) levels in the paraventricular nucleus (PVN) of the hypothalamus. We hypothesized that leptin suppresses stress axis activity in T1D through central and peripheral mechanisms. In the first experiment, adult male Sprague Dawley rats were implanted with a cannula in the PVN and randomly divided into a non-diabetic group treated with vehicle (n = 6) and a diabetic group treated with streptozotocin (n = 13). Food intake and water intake was measured for 14 days. On the last day, a subset of diabetic rats were treated with 500 µg of leptin i.p. Rats were subjected to push-pull perfusion of the PVN and hourly blood sampling for 5 h. In the next experiment, diabetic rats were treated either with an alpha-2 adrenergic agonist, clonidine (CLON), or a beta adrenergic agonist isoproterenol (ISO), to reverse the effects of leptin. Rats were subjected to push pull perfusion and hourly blood sampling. In experiment 1, T1D increased food intake, water intake, NE release in the PVN and circulating CS levels. Leptin treatment decreased NE release modestly but produced a robust reduction in corticosterone (CS) levels. In experiment 2, CLON but not ISO was able to reverse the effect of leptin on NE levels in the PVN, however, both agonists were capable of blocking leptin's effects on circulating CS. These results suggest that in diabetic rats, the sensitivity of the hypothalamus to beta adrenergic agonists is altered, while the adrenals remain sensitive to both alpha and beta adrenergic agonists. [ABSTRACT FROM AUTHOR]

Background: Chronic stress, an important factor in the development of depressive disorders, leads to an increased formation of cortisol, which causes a hyperactivity of the hypothalamic-pituitary-adrenal (HPA) axis. In addition, cortisol mediates an adaptive effect on plasma membrane fluidity which may affect signal transduction of membrane-bound receptors and contribute to pathophysiological changes.Methods: Membrane fluidity was measured by fluorescence anisotropy using DPH (1,6-diphenyl-1,3,5-hexatriene) and TMA-DPH (1-(4-(trimethylamino)phenyl)-6-phenylhexa-1,3,5-triene). Changes in cellular content of phosphatidylcholine species was determined by pulse-chase experiments using deuterated choline and mass spectrometry. Single molecule tracking was used to examine the lateral mobility of β1-adrenoceptors and changes in cAMP formation were measured by ELISA.Results: Chronic exposure (6 - 8 days) of C6 cells to cortisol dose-dependently decreased DPH and TMA-DPH fluorescence anisotropy, reflecting increased membrane fluidity. In contrast, cells pretreated with St. John's wort extract Ze117 showed increased DPH and TMA-DPH fluorescence anisotropy values, indicating a membrane rigidification effect which was mediated at least by the constituents hypericin, hyperforin, quercetin, amentoflavone and biapigenin. The observed membrane fluidizing effect of cortisol could be reversed by cotreatment with Ze117. The membrane rigidification of Ze117 was in line with the in parallel observed decrease in the phosphatidylcholine/phosphatidylethanolamine ratio determined in whole cell lipid extracts. Interestingly, pulse-chase experiments demonstrated, that Ze117 inhibited the incorporation of choline-D9 in phosphatidylcholine species with saturated or monounsaturated fatty acids compared to control cells, while the synthesis of phosphatidylcholine species with polyunsaturated fatty acids was not affected. C6 cells whose membranes have become more rigid by Ze117 showed altered lateral mobility of β1-adrenoceptors as well as reduced cAMP formation after stimulation with the β1-adrenoceptor agonist dobutamine.Conclusion: Obviously, the signaling of β1-adrenoceptors depends on the nature of the membrane environment. It can therefore be assumed that Ze117 has a normalizing effect not only on the membrane fluidity of "stressed" cells, but also on lateral mobility and subsequently on the signal transduction of membrane-associated receptors. [ABSTRACT FROM AUTHOR]

Abstract: The stress axis in teleost fish attempts to maintain internal homeostasis in the face of allostatic loading. However, stress axis induction has been associated with a higher predation rate in fish. To date, the physiological and behavioral factors associated with this outcome are poorly understood. The purpose of the present study was to investigate the impact of experimental cortisol elevation on anti‐predator behavior and physiological responses to predator presence. We hypothesized that semi‐chronic cortisol elevation would increase susceptibility to predation by increasing stress‐induced risk‐taking behaviors. To test this hypothesis, schoolmaster snapper were given cocoa butter implants without cortisol (sham) or with cortisol (50 mg/kg body weight) and tethered to cover. Fish were exposed to either a lemon shark or control conditions for 15‐min. Space use and activity were recorded throughout and fish were terminally sampled for blood. Cortisol implantation, relative to shams, resulted in higher blood glucose and plasma cortisol concentrations with a lower plasma lactate concentration. Shark exposure, relative to controls, elicited higher blood glucose and lactate concentrations but had no effect on plasma cortisol concentration. No interactions were detected between shark exposure and cortisol treatment for any physiological trait. Behavioral metrics, including shelter use and activity, were unaffected by either cortisol implantation or shark exposure. Physiological responses to cortisol implantation likely resulted from enhanced gluconeogenic activity, whereas alterations under predator exposure may have been the product of catecholamine mobilization. Further work should address context‐specific influences of stress in mediating behavioral responses to predation. [ABSTRACT FROM AUTHOR]

Aim. The aim of this study was to analyze the expression of 3 genes involved in the regulation of HPA axis: GR, HSP90 and FKBP5, in patients with major depressive disorder (MDD) before antidepressant treatment and after 8 weeks of pharmacotherapy. Additionally, we analyzed the level of glucocorticoid receptor isoforms before and after treatment. Methods. The study included 30 female patients (aged 18-60 years), with major depressive disorder diagnosed on the basis of the Structured Clinical Interview for DSM-IV (SCID). Antidepressant treatment included use of sertraline or venlafaxine. The assessment of patients' mental state (severity of depression) was checked by the Hamilton Depression Rating Scale (HDRS). After 8 weeks of treatment, the same clinical and molecular tests were performed. All of the patients underwent dexamethasone suppression test (DST). MRNA was isolated from the peripheral blood to evaluate the expression of the studied genes using real-time PCR with TaqMan probes. The concentration of GR isoforms (α and β) in serum was also determined using ELISA. Statistical analysis was performed using Statistica v.12.0 software. Results. The abnormal cortisol level was only seen in 20% of patients. Dysregulation on HPA axis was observed in 10% of patients. We observed significant clinical improvement after 8 weeks of pharmacotherapy in all patients. Almost the whole group of patients (except one patient) showed full remission of symptoms. We observed significant moderate correlation between cortisol level after DST before treatment and after 8 weeks of pharmacotherapy (r2 = 0.44). The results showed no significant difference in the expression of 3 analyzed genes compared before and after 8 weeks of therapy. The results of ELISA showed decreased level of α isoform after pharmacotherapy, independent of drug. Conclusions. The results showed no significant changes in the expression of genes involved in the stress axis activity during antidepressant therapy. [ABSTRACT FROM AUTHOR]

Objectives:Despite considerable knowledge regarding the importance of stress in coronary artery disease (CAD) pathogenesis, its underestimation persists in routine clinical practice, in part attributable to lack of a standardized, objective assessment. The current study examined the ability of stress hormones to predict CAD severity and prognosis at basal conditions as well as during and following an exertional stimulus. Materials and methods:Forty Caucasian subjects with significant coronary artery lesions (≥50%) were included. Within 2 months of coronary angiography, cardiopulmonary exercise testing (CPET) on a recumbent ergometer was performed in conjunction with stress echocardiography (SE). At rest, peak and after 3 min of recovery following CPET, plasma levels of cortisol, adrenocorticotropic hormone (ACTH) and NT-pro-brain natriuretic peptide (NT-pro-BNP) were measured by immunoassay sandwich technique, radioimmunoassay, and radioimmunometric technique, respectively. Subjects were subsequently followed a mean of 32 ± 10 months. Results and discussion:Mean ejection fraction was 56.7 ± 9.6%. Subjects with 1–2 stenotic coronary arteries (SCA) demonstrated a significantly lower plasma cortisol levels during CPET compared to those with 3-SCA (p < .05), whereas ACTH and NT-pro-BNP were not significantly different (p > .05). Among CPET, SE, and hormonal parameters, cortisol at rest and during CPET recovery demonstrated the best predictive value in distinguishing between 1-, 2-, and 3-SCA [area under ROC curve 0.75 and 0.77 (SE = 0.11, 0.10;p = .043, .04) for rest and recovery, respectively]. ΔCortisol peak/rest predicted cumulative cardiac events (area under ROC curve 0.75, SE = 0.10,p = .049). Conclusions:Cortisol at rest and following an exercise test holds predictive value for CAD severity and prognosis, further demonstrating a link between stress and unwanted cardiac events. [ABSTRACT FROM AUTHOR]

In this paper we present a comprehensive database of 152 earthquake focal mechanism solutions for the Nordland area, northern Norway, and the adjacent offshore regions. 123 focal mechanisms are published for the first time. We developed an equation to objectively determine the quality of the focal mechanisms, while the equation was explicitly adjusted to the used dataset (not globally accepted). We used the equation to assign quality factors to the new focal mechanisms, while the quality of the earlier published focal mechanisms was kept as originally provided. About 20% of all focal mechanisms were set to the higher quality A and B, which was assigned to the onshore earthquakes only, whereas for offshore earthquakes the highest assigned quality was quality C, mostly due to larger azimuthal gaps. The results showed that seismicity onshore and offshore Nordland is different in type: with dominant shallow, normal-faulting earthquakes onshore and mostly deeper, mixed type faulting earthquakes offshore, while along the coast the faulting regime was mostly normal to strike-slip. The results indicated that maximum horizontal compressional stress, sH, directions in the offshore areas on a large scale originate from the plate-tectonic ridge push with NW--SE compression, whereas in the onshore regions sH directions are better explained through local stress-generating sources, such as topography. In our results we also recognised a possible relation between the Svartisen glacier massif and the enhanced seismicity in the surroundings, including an earthquake swarm activity to the west of the glacier. Moreover, in many onshore and offshore regions the nodal plane azimuths, obtained from the focal mechanisms, correlate well with the trends of geologically mapped onshore and offshore structures. [ABSTRACT FROM AUTHOR]

Disruption of non-reproductive endocrine systems in wildlife by chemicals has received little attention but represents a potentially significant problem. Nitrate is a major anthropogenic contaminant in the freshwater aquatic environment and has been identified as a potential disrupter of endocrine function in aquatic animals. This study was conducted to investigate the relationship between the function of the neuroendocrine stress axis in fish and inorganic N loading along reaches of rivers receiving cumulative point source and diffuse chemical inputs. To accomplish this, the responsiveness of the stress axis, quantified as the rate of release of cortisol to water across the gills during exposure to a standardised stressor, was measured in three-spined sticklebacks ( Gasterosteus aculeatus L.) resident at three sites on each of four rivers in north-west England. The magnitude of the stress response in fish captured at the sites furthest downstream on all rivers was more than twice that of fish captured at upstream sites. Site-specific variation in stress axis reactivity was better explained by between-site variation in concentrations of dissolved nitrate, nitrite, and ammonia than by the concentration of wastewater treatment works effluent. An increase in the magnitude of the stress response was seen among sticklebacks at sites where long-term averaged concentrations of NH 3 -N, NO 3 -N and NO 2 -N exceeded 0.6, 4.0 and 0.1 mg/L respectively. These data suggest that either (i) inorganic N is a better surrogate than wastewater effluent concentration for an unknown factor or factors affecting stress axis function in fish, or (ii) dissolved inorganic N directly exerts a disruptive influence on the function of the neuroendocrine stress axis in fish, supporting concerns that nitrate is an endocrine-modulating chemical. [ABSTRACT FROM AUTHOR]

Tectonophysical studies are conducted in South Sakhalin for identification of temporal-spatial changes in the geodynamic settings of the formation of the local structures. Analysis of the field data reveals 11 local stress state (LSS) in the large newest megastructures, which were formed on geological basement of different ages. The parameters of the tectonic stresses are significantly distinct in each LSS, especially the orientations (up to reindexation) of the compression and extension axes in different fault wings. Tectonic stresses of two ages and constant latitudinal and horizontal compression axis are reconstructed. The earlier cofold shear stress field with a horizontal and longitudinal extension axis is post-Miocene and the later stress field of the reversed fault with a vertical extension axis is orogenic. The LSSs reconstructed for the first time by the displacement vectors on slickensides, along with the data on the earthquake mechanisms, substantiate the reindexation of the horizontal extension axis with the vertical intermediate axis of major normal stresses at the postfold orogenic stage of evolution of the territory. These results are in agreement with previous data on the transformation of the dextral to reverse thrust displacements along the longitudinal fault systems. The young stress field is more confidently interpreted in the activation fault zones, which limit the orogenic blocks, whereas the traces of cofold deformations without younger orogenic stress fields better remain inside the blocks which are composed of older and strongly dislocated Mesozoic rocks. [ABSTRACT FROM AUTHOR]

Background: Genes associated with the physiological response to stress in the hypothalamic-pituitary-adrenal axis are considered as good candidates for genetic research in borderline personality disorder (BPD).Methods: In this study, five FKBP5 (a co-chaperone of the glucocorticoid receptor) SNPs (rs3800373, rs9296158, rs737054, rs1360780, rs9470080) were genotyped in a sample of 101 unrelated Caucasian patients with BPD and 111 ethnically matched healthy controls. The interaction between FKBP5 polymorphisms and childhood trauma was also tested.Results: All FKBP5 polymorphisms genotyped showed significant associations with BPD. A main effect of rs9470080 (p = 0.01) and gene x environment (physical abuse) interaction (p = 0.01) was found. A gene x environment (emotional abuse) interaction was also found for rs3800373 (p = 0.03). However, these interactions did not remain significant after multiple testing corrections.Limitations: In this study, only 5 genetic variants were tested and thus tagging of the FKBP5 gene was incomplete. Moreover, the sample size is moderate.Conclusion: BPD is associated with FKBP5 polymorphisms and several types of childhood abuse may modulate the effect between FKBP5 SNPs and this disorder. [ABSTRACT FROM AUTHOR]

The hypothalamic neuropeptide oxytocin (OT) is well known for its prosocial, anxiolytic, and ameliorating effects on various psychiatric conditions, including alcohol use disorder (AUD). In this chapter, we will first introduce the basic neurophysiology of the OT system and its interaction with other neuromodulatory and neurotransmitter systems in the brain. Next, we provide an overview over the current state of research examining the effects of acute and chronic alcohol exposure on the OT system as well as the effects of OT system manipulation on alcohol-related behaviors in rodents and humans. In rodent models of AUD, OT has been repeatedly shown to reduce ethanol consumption, particularly in models of acute alcohol exposure. In humans however, the results of OT administration on alcohol-related behaviors are promising but not yet conclusive. Therefore, we further discuss several physiological and methodological limitations to the effective application of OT in the clinic and how they may be mitigated by the application of synthetic OT receptor (OTR) agonists. Finally, we discuss the potential efficacy of cutting-edge pharmacology and gene therapies designed to specifically enhance endogenous OT release and thereby rescue deficient expression of OT in the brains of patients with severe forms of AUD and other incurable mental disorders., (© 2023. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

It has now become accepted that the immune system and neuroendocrine system form an integrated part of our physiology. Immunological defense mechanisms act in concert with physiological processes like growth and reproduction, energy intake and metabolism, as well as neuronal development. Not only are psychological and environmental stressors communicated to the immune system, but also, vice versa , the immune response and adaptation to a current pathogen challenge are communicated to the entire body, including the brain, to evoke adaptive responses (e.g., fever, sickness behavior) that ensure allocation of energy to fight the pathogen. This phenomenon is evolutionarily conserved. Hence it is both interesting and important to consider the evolutionary history of this bi-directional neuroendocrine-immune communication to reveal phylogenetically ancient or relatively recently acquired mechanisms. Indeed, such considerations have already disclosed an extensive “common vocabulary” of information pathways as well as molecules and their receptors used by both the neuroendocrine and immune systems. This review focuses on the principal mechanisms of bi-directional communication and the evidence for evolutionary conservation of the important physiological pathways involved. [ABSTRACT FROM AUTHOR]

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 exclusively in females. [ABSTRACT FROM AUTHOR]

In vertebrates, the hypothalamus-pituitary-adrenal gland (HPA) axis is the main endocrine pathway regulating the stress response, thus also called the stress axis. It has been well-accepted that the stress axis is tightly controlled by both hypothalamic stimulators and inhibitors [e.g. corticotropin (ACTH)-releasing inhibitory factor (CRIF)]. However, the identity of authentic CRIF remains unclear for decades. Recently, neuropeptide W (NPW) was proved to be the physiological CRIF in chickens. Together with its functional receptor (NPBWR2), they play critical roles in attenuating the activity of the chicken stress axis. Because increasing pieces of evidence suggested that sex steroids could regulate the stress axis, using chicken as a model, we investigated whether the newly identified CRIF and its receptor are under the control of sex steroids in this study. Our results showed that: (1) expression of NPW-NPBWR2 in the hypothalamus-pituitary axis was sexually dimorphic and developmental stage-dependent; (2) progesterone (P 4), rather than 17β-estradiol (E 2) and dihydrotestosterone (DHT), could dose- and time-dependently upregulate NPBWR2 expression, which was accompanied with the decrease of ACTH synthesis and secretion, in cultured pituitary cells; (3) intraperitoneal injection of P 4 could elevate the mRNA level of pituitary NPBWR2 ; (4) P 4 -stimulated NPBWR2 expression was relevant to both nPR-mediated genomic action and mPRs-triggered nongenomic route associated with MEK/ERK, PI3K/AKT cascade, and calcium influx. To our knowledge, our results discover a novel route of sex steroids in modulating the stress axis of chickens, which lays a foundation to reveal the complicated interaction network between reproduction and stress axes in chickens. • Expression of NPBWR2 varied with gender and developmental stage in chicken pituitary. • P 4 , rather than E2 and DHT, can upregulate NPBWR2 expression in chicken pituitary. • P 4 can inhibit pituitary ACTH synthesis/release in chickens. • P 4 -triggered action is relevant to both nuclear and membrane-anchored receptors. • The mPRs-related role is mediated via MEK/ERK, PI3K/AKT cascade, and Ca2+ influx. [ABSTRACT FROM AUTHOR]