Activation Of Stress Axis Research Articles

Skin swabbing protocol to collect DNA samples from small-bodied fish species

Fish species are commonly used as experimental models in the laboratory. DNA is routinely collected from these animals to permit identification of their genotype. The current standard procedure to sample DNA is fin clipping, which involves anaesthetising individuals and removing a portion of the caudal fin. While fin clipping reliably generates good quality DNA samples for downstream applications, there is evidence that it can alter health and welfare, and impact the fish’s behaviour. This in turn can result in greater variation in the data collected. In a recent study we adapted a skin swabbing protocol to collect DNA from small-bodied fish, including sticklebacks and zebrafish, without the use of analgesics, anaesthetics or sharp instruments. A rayon-tipped swab was used to collect mucus from the flank of the fish, which was then used for DNA extraction. We subsequently demonstrated that compared to fin clipping, skin swabbing triggered fewer changes in stress axis activation and behaviour. We also found that gene expression and behaviour data collected from swabbed fish were less variable than similar data collected from fish that had been fin clipped. This potentially allows smaller sample sizes in experimental groups to be used after skin swabbing, thereby reducing animal use. Here we provide a detailed protocol explaining how to collect DNA samples from small laboratory fish using skin swabs.

Macrophage-specific deletion of Notch-1 induced M2 anti-inflammatory effect in atherosclerosis via activation of the PI3K-oxidative stress axis.

Notch-1 signaling is significantly associated with the occurrence and development of atherosclerosis (AS). However, the molecular mechanisms underlying the specific deletion of Notch-1 in AS-associated macrophages are not fully understood. This study aimed to investigate the effects of Notch-1 in AS. Tissue samples were obtained from atherosclerotic segments of human carotid arteries. Immunofluorescence staining showed that Notch-1 was significantly colocalized with macrophages (CD68+), and Notch-1 staining was increased in human vulnerable plaques. Notch-1MAC-KO/ApoE-/- mice were generated in which Notch-1 was selectively inactivated in macrophages, and WT for littermate control mice (ApoE-/-/Notch-1WT). A control group was then established. All mice fed with a high-fat and Oil Red O, Movat, a-SMA, CD68, and Sirius red staining were used to evaluate the morphology. Specific deletion of Notch-1 in macrophages repressed the pathophysiology of AS. Immunofluorescent staining and Western blotting revealed that Notch-1MAC-KO repressed M1 and M2 responses in AS. Here, GSEA revealed that Notch-1 activation and PI3K signaling were statistically significantly correlated with each other, and Notch-1 was involved in the regulation of the PI3K signaling pathway. In the in vitro experiments, the secretion of Arg-1 and exosomes was classified by peritoneal macrophages of Notch-1MAC-KO/ApoE-/- and Notch-1WT/ApoE-/- mice. Immunohistochemistry staining and Western blotting were used to measure the expression levels of Notch1, PI3K, p-PI3K, AKT, p-AKT, Arg-1, IL-6, CD36, SREBP-1, CD206, iNOS, cleaved-caspase-3/-9, Bax, CD9, Alix and TSG101 in the peritoneal macrophages and exosomes, respectively. The specific deletion of Notch-1 in macrophage represses the formation and development of AS via the PI3K/AKT signaling pathway.

The relationship between self-reported chronic stress, physiological stress axis dysregulation and medically-unexplained symptoms

The positive feedback model of medically-unexplained symptoms posits that chronic stress affects the activity of the physiological stress axes, which in turn generates medically-unexplained symptoms. As a first step to empirically test its model assumptions, we investigated potential associations between chronic stress, physiological stress axis activity and medically-unexplained in a cross-sectional study. One hundred-ninety-nine healthy individuals provided self-reports on chronic stress and medically-unexplained symptoms, resting heart rate/variability (HR/HRV; e.g., root mean square of successive differences/RMSSD, low frequency/LF power), cortisol awakening response (CAR) and diurnal cortisol. Significant positive contributors to medically-unexplained symptoms were the chronic stress scales ‘lack of social appreciation’ and ‘chronic worries’, as well as CAR and LF HRV; diurnal cortisol was a negative contributor. Mediation analyses showed that the impact of neural indicators associated with physiological stress axis activity (HR/HRV) related to medically-unexplained symptoms, which was mediated by chronic stress, whereas the mediation effect as suggested by the positive feedback model was not significant. These cross-sectional findings do not support the positive feedback model. Longitudinal studies are required to conclude about potential mechanistic and causal relationships in the model. Nevertheless, our mediation analyses give first indication that the constitution of physiological stress axes may play a major role in how stressors are perceived and which kind of health-consequences (e.g., medically-unexplained symptoms) this may have.

Assessing Chronodisruption Distress in Goldfish: The Importance of Multimodal Approaches.

Chronodisruption caused by factors such as light at night and mistimed meals has been linked to numerous physiological alterations in vertebrates and may be an anxiogenic factor affecting welfare. This study aims to investigate whether chronodisruption causes measurable changes in the anxiety responses of goldfish under two conditions: randomly scheduled feeding (RF) and continuous light (LL). Anxiety-like behavior was assessed in the open field with object approach and black/white preference tests, which had been validated using diazepam. An increased thigmotaxis response and decreased object exploration under both chronodisruption protocols indicated anxiety states. Furthermore, locomotor activity was increased in LL fish. The black/white preference test discriminated anxiolysis induced by diazepam but was unable to detect anxiety caused by chronodisruption. Plasma cortisol increased in both RF and LL fish throughout the experiment, confirming that both conditions caused stress. The LL fish also showed an apparently desensitized hypothalamus-pituitary-interrenal HPI axis, with a decrease in pomc and crf expression. Individual analysis found no correlation between anxiety-like behavior and stress axis activation nor between scototaxis and thigmotaxis responses. However, individual differences in sensitivity to each test were detected. Altogether, these results highlight circadian disruption as a stressor for fish and endorse a multiple variable approach for reliably assessing animal discomfort.

Copeptin response to panic provocation with CO2 in healthy adults

Repeated panic attacks are the core symptom of panic disorder and severely stressful for patients. Additional to the psychological response, the physiological symptoms are an important aspect of the experienced panic. However, data on the extent of hypothalamic-pituitary-adrenal (HPA)-axis activation during panic attacks is inconsistent. Therefore, in the present study, we aimed at investigating the stress-axis activity in more detail by including Copeptin (CoP) as a stable surrogate parameter for the vasopressinergic hypothalamic activity during experimentally induced panic attacks in healthy adults (N = 21). During a placebo-controlled panic challenge with 35% CO2 compared to normal air inhalation, we measured CoP and the peripheral effector hormones Adrenocorticotropic Releasing Hormone (ACTH) and cortisol in plasma along with the psychological response to panic anxiety. We analyzed hormonal secretion patterns, their correlations and individual panic ratings over time and explored differences between female and male participants. We found a significant CO2-induced increase of CoP plasma levels and psychological panic symptoms after CO2-administration, while no positive correlations of CoP levels with the peripheral HPA-axis hormones and with panic symptoms were present. No differences between female and male participants concerning their psychological response nor their baseline CoP levels, the release of CoP or its increase during the experiment were found. CoP could be a sensitive indicator for an organism's physiologic acute hypothalamic response during stress and panic attacks.

Stress and sleep disturbances in COVID-19 pandemic, current neurology and psychology aspects: a narrative review

Pandemic is a phenomenon that has been occurring for decades. In the past two years, the world has again faced a pandemic situation due to coronavirus disease-19 (COVID-19) caused by severe acute respiratory syndrome coronavirus (SARS-CoV). The COVID-19 pandemic has brought the world to a standstill. People also experience psychological stress conditions in the form of anxiety, worry, and anger due to the social impacts caused by the COVID-19 pandemic as has happened in other countries. Social distancing regulations lead to an increase in psychiatric symptoms, including stress, anxiety, depression, and sleep disturbances. Sleep disturbances can also have a negative impact on health, quality of work, and the risk of bad behavior or events in the workplace, as well as the risk of work-related accidents or injuries. There is a correlation between the SARS-CoV-2 pandemic and the neuroendocrine stress axis. The ability of an organism to adapt to the stressors encountered involves the sympathoadrenal system and the hypothalamic-pituitary-adrenal (HPA) axis. The interactions between these two systems play an important role in adaptation. Excessive or chronic activation of the endocrine stress axis, which also causes feedback loop disruption, triggers and contributes to a variety of stress disorders and conditions in humans, including anxiety, sleep disorders, post-traumatic stress disorder, major depressive disorder, and job burnout.

The environmental and social stress perception in autism spectrum disorder – focusing on stress coping mechanisms and gastrointestinal manifestations

IntroductionAutism spectrum disorder (ASD) is currently defined as persistent deficits in social communication and social interaction additional to repetitive behavioural patterns, and restrictive interests or activities. Several studies suggested that ASD is accompanied by defective perception and altered response to the environmental factors, including environmental and social stress. In this context, frequent reports addressed the manifestation of different stress-related behavioural and physiological patterns, such as restless leg syndrome, migraine, and functional gastrointestinal disorders (FGIDs). Thus, a major problem in ASD patients’ management could be related to the exacerbated effects of stress.ObjectivesIn this study, we aimed to find a correlation between the stress perception and response and the manifestation of some neurological and FGIDs in ASD.MethodsThe main scientific databases were screened for studies describing the effects of stress in autism patients and animal models. Exclusion criteria: (1) studies not written in English language; (2) not available as full text; (3) not describing stress response; and/or (2) functional gastrointestinal manifestations in autism.ResultsThe repetitive behaviours have a heterogenous pattern in both severity and manifestations, varying from repetitive motor movements and inflexible adherence to routines to hypo- or hyper-reactivity to exterior stimuli. Moreover, some studies describe repetitive behaviours as altered stress coping mechanisms meant to relieve anxious states – one of the main stress axis activation effects. We recently described some significantly reported FGID-like manifestations in ASD that could be the result of various abnormalities in the brain – gut interaction, such as impaired parasympathetic activity and increased endocrine stress response. In this context, there could be a correlation between the altered perception and response to stress and the FGID-like manifestations, as we previously described the stress axis implication in one of the most common FGID, irritable bowel syndrome – which is also frequently reported in ASD cases.ConclusionsIn ASD, the perception and response to environmental and social stress could be impaired. Thus, impaired stress coping mechanisms, defective stress axis, and altered behavior could lead to stress-specific manifestations, such as restless leg syndrome, migraine, and irritable bowel syndrome.Funding: *B. I.-M. and *R. M.-A. are supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational ProgramDisclosure of InterestI. M. Balmus Grant / Research support from: B. I.-M. is supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., M. A. Robea Grant / Research support from: R. M.- A. is supported by the Project POCU/993/6/13/153322 ”Suport educațional și formativ pentru doctoranzi și tineri cercetători în pregătirea inserției în piața muncii” of the European Social Fund through the Human Capital Operational Program., R. Lefter: None Declared, A. Ciobica: None Declared, L. Gorgan: None Declared, C. Stanciu: None Declared, A. Trifan: None Declared

Abstract 12407: Hypothalamic-Pituitary Adrenal Axis Activation in Women With Takotsubo Syndrome

Introduction. Takotsubo Syndrome (TS) has been associated with acute stress exposure and excessive activation of the adrenergic nervous system. Less is known about the role of chronic stress and of the hypothalamic-pituitary-adrenal (HPA) axis in the pathophysiology of TS. Hair cortisol concentration (HCC) is a novel biomarker of chronic stress and HPA axis activation. Plasma cortisol is incorporated in growing hair (average growth rate = 1 cm/month), reflecting HPA axis activity over the preceding months. In this study we measured HCC in TS patients and explored associations between HCC, trigger status, and psychological characteristics at enrollment. Methods. HCC was measured in a group of patients admitted with a new TS diagnosis based on Mayo Clinic criteria (n=18). Demographics, perceived stress, depression, anxiety, PTSD symptoms, coping skills, and resilience (self-report questionnaires); trigger history (standardized in-person interview); and HCC were collected at the baseline visit. Hair strands were cut near the scalp from a posterior vertex position. HCC was measured in the first 3 cm of hair, which reflects plasma cortisol levels during the previous 3 months. Samples were washed, ground, extracted in HPLC-grade methanol, and quantified (pg/mg) using a high-sensitivity enzyme immunoassay (EIA) kit. Descriptive statistics were used to characterize the sample, and Spearman rho to examine associations. A p value (2-sided) < .05 was considered significant. Results. Participants were 65.6 (SD 9.4) years old, 100% female, 100% white, 10% Hispanic. 52% married/living as married. Median HCC was 6.35 pg/mg (IQR 3.6, 15.2). HCC was significantly higher in patients reporting no triggers vs. those reporting a trigger prior to the TS episode (14.9 vs. 6.8 pg/ml, p=0.03). No associations were found between psychological measures and HCC, except for a non-significant inverse association between HCC and PTSD symptoms (rho=-0.35; p=0.14). Conclusions. This first exploration of HCC levels in patients with a recent TS episode suggests that chronic HPA axis activation likely does not play a role in the pathophysiology of TS. Findings need to be confirmed in a controlled study with a larger and more diverse sample.

Does stress predict the development of internalizing symptoms in middle childhood? An examination of additive, mediated, and moderated effects of early family stress, daily interpersonal stress, and physiological stress.

Early life stress, daily life experiences, and the stress responsive hypothalamic-pituitary-adrenal (HPA) axis have each been examined as predictors of the development of psychopathology. Rarely have researchers attempted to understand the covariation or interaction among these stress domains using a longitudinal design in the prediction of symptoms of internalizing psychopathology, particularly during childhood. This study examined early family stress, daily interpersonal stress, indicators of diurnal cortisol, and internalizing symptoms in a racially/ethnically and socioeconomically diverse sample of twins (N = 970 children; Mage at outcome = 9.73; 52% female; 23.7% Hispanic/Latino, 58.8% White; 30% below middle class; Lemery-Chalfant et al., 2019). An additive model of stress, a stress mediation model, and a stress sensitization framework model each delineated potential pathways linking stress and internalizing symptoms. Supporting additive pathways, multilevel models showed that all 3 stress indicators uniquely predicted internalizing symptoms. There was a significant indirect path from early family stress to 9 year internalizing symptoms through interpersonal stress, supporting stress mediation. Family stress moderated the association between interpersonal stress and internalizing symptoms, though not in the direction that would support stress sensitization. Child stress, including daily interpersonal stress and HPA axis activity, and internalizing symptoms are prevalent and family stress is a significant precursor to child internalizing symptoms across child development. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Physiological behavior during stress anticipation across different chronic stress exposure adaptive models

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, ΔNT-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.

Skin swabbing protocol to collect DNA samples from small-bodied fish species.

Fish species are commonly used as experimental models in the laboratory. DNA is routinely collected from these animals to permit identification of their genotype. The current standard procedure to sample DNA is fin clipping, which involves anaesthetising individuals and removing a portion of the caudal fin. While fin clipping reliably generates good quality DNA samples for downstream applications, there is evidence that it can alter health and welfare, and impact the fish's behaviour. This in turn can result in greater variation in the data collected. In a recent study we adapted a skin swabbing protocol to collect DNA from small-bodied fish, including sticklebacks and zebrafish, without the use of analgesics, anaesthetics or sharp instruments. A rayon-tipped swab was used to collect mucus from the flank of the fish, which was then used for DNA extraction. We subsequently demonstrated that compared to fin clipping, skin swabbing triggered fewer changes in stress axis activation and behaviour. We also found that gene expression and behaviour data collected from swabbed fish were less variable than similar data collected from fish that had been fin clipped. This potentially allows smaller sample sizes in experimental groups to be used after skin swabbing, thereby reducing animal use. Here we provide a detailed protocol explaining how to collect DNA samples from small laboratory fish using skin swabs.

Hypocaloric Dieting Unsettles the Neuroenergetic Homeostasis in Humans.

Background: The effects of low-calorie dieting in obesity are disappointing in the long run. The brain’s energy homeostasis plays a key role in the regulation of body weight. We hypothesized that the cerebral energy status underlies an adaptation process upon body weight loss due to hypocaloric dieting in humans. Objective: We instructed 26 healthy obese participants to reduce body weight via replacement of meals by a commercial diet product for two weeks. The cerebral energy status was assessed by 31 phosphorus magnetic resonance spectroscopy (31 PMRS) before and after low-caloric dieting as well as at follow-up. A standardized test buffet was quantified after body weight loss and at follow-up. Blood glucose metabolism and neurohormonal stress axis activity were monitored. Results: Weight loss induced a decline in blood concentrations of insulin (p = 0.002), C-peptide (p = 0.005), ACTH (p = 0.006), and norepinephrine (p = 0.012). ATP/Pi (p = 0.003) and PCr/Pi ratios (p = 0.012) were increased and NADH levels reduced (p = 0.041) after hypocaloric dieting. At follow-up, weight loss persisted (p < 0.001), while insulin, C-peptide, and ACTH increased (p < 0.005 for all) corresponding to baseline levels again. Despite repealed hormonal alterations, ratios of PCr/Pi remained higher (p = 0.039) and NADH levels lower (p = 0.007) 6 weeks after ending the diet. ATP/Pi ratios returned to baseline levels again (p = 0.168). Conclusion: Low-calorie dieting reduces neurohormonal stress axis activity and increases the neuroenergetic status in obesity. This effect was of a transient nature in terms of stress hormonal measures. In contrast, PCr/Pi ratios remained increased after dieting and at follow-up while NADH levels were still reduced, which indicates a persistently unsettled neuroenergetic homeostasis upon diet-induced rapid body weight loss.

Loneliness Mediates the Relationship Between Early Life Stress and Perceived Stress but not Hypothalamic-Pituitary-Adrenal Axis Functioning.

Many authors have proposed that early life stress (ELS) provokes a dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis and contributes negatively to the management of stress in adulthood. However, these associations have not always been observed, making it necessary to include new factors that could explain the different results found. In this regard, people with ELS experiences report less social support during adulthood, suggesting that loneliness could be a mediating factor. Thus, our aims were to investigate whether ELS was related to both perceived stress and diurnal HPA axis activity, and whether loneliness mediates these relationships, in a community sample (N=187, 18–55years old). Fourteen cortisol samples were collected on two non-consecutive days to obtain the overall diurnal cortisol, diurnal cortisol slope, and bedtime levels. Additionally, ELS was assessed with the Risky Families Questionnaire (RFQ) and the Recalled Childhood and Adolescence Perceived Stress (ReCAPS) measure. Results revealed that ELS was associated with perceived stress, but not HPA axis functioning, and loneliness mediated the relationship between ELS and perceived stress, but not between ELS and HPA axis functioning. Similar results were found for both ELS questionnaires, suggesting that the ReCAPS is an adequate tool. These results highlight the importance of loneliness in understanding the long-term effects of ELS, and they indicate different effects of ELS on subjective and physiological stress indicators.

Aerobic Exercise and Stretching as Add-On to Inpatient Treatment for Depression Have No Differential Effects on Stress-Axis Activity, Serum-BDNF, TNF-Alpha and Objective Sleep Measures

(1) Background: While the antidepressant effects of aerobic exercise (AE) are well documented, fewer studies have examined impact of AE as an add-on treatment. Moreover, various effects on neurobiological variables have been suggested. This study examines effects of AE on Cortisol Awakening Reaction (CAR), serum Brain Derived Neurotrophic Factor (sBDNF), Tumor Necrosis Factor alpha (TNF-alpha) and sleep. (2) Methods: Inpatients with moderate-to-severe depression (N = 43) were randomly assigned to the AE or stretching condition (active control) taking place 3x/week for 6 weeks. CAR, sBDNF and TNF-alpha were assessed at baseline, after 2 weeks and post-intervention. The 17-item Hamilton Depression Rating Scale (HDRS17), subjective sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI) and polysomnography (PSG) were obtained at baseline and post-intervention. (3) Results: Stress axis activity decreased in both groups from baseline to post-intervention. sBDNF showed a significant increase over time, whereas the number of awakenings significantly decreased. No significant time by group interactions were detected for any of the study variables. Correlational analyses showed that higher improvements in maximum oxygen capacity (VO2max) from baseline to post-intervention were associated with reduced scores on the HDRS17, PSQI and REM-latency post-intervention. (4) Conclusions: While some neurobiological variables improved during inpatient treatment (CAR, sBDNF), no evidence was found for differential effects between AE and an active control condition (stretching). However, patients in which cardiorespiratory fitness increased showed higher improvements in depression severity and depression-related sleep-parameters.

Stress hormones mediate developmental plasticity in vertebrates with complex life cycles

The environment experienced by developing organisms can shape the timing and character of developmental processes, generating different phenotypes from the same genotype, each with different probabilities of survival and performance as adults. Chordates have two basic modes of development, indirect and direct. Species with indirect development, which includes most fishes and amphibians, have a complex life cycle with a free-swimming larva that is typically a growth stage, followed by a metamorphosis into the adult form. Species with direct development, which is an evolutionarily derived developmental mode, develop directly from embryo to the juvenile without an intervening larval stage. Among the best studied species with complex life cycles are the amphibians, especially the anurans (frogs and toads). Amphibian tadpoles are exposed to diverse biotic and abiotic factors in their developmental habitat. They have extensive capacity for developmental plasticity, which can lead to the expression of different, adaptive morphologies as tadpoles (polyphenism), variation in the timing of and size at metamorphosis, and carry-over effects on the phenotype of the juvenile/adult. The neuroendocrine stress axis plays a pivotal role in mediating environmental effects on amphibian development. Before initiating metamorphosis, if tadpoles are exposed to predators they upregulate production of the stress hormone corticosterone (CORT), which acts directly on the tail to cause it to grow, thereby increasing escape performance. When tadpoles reach a minimum body size to initiate metamorphosis they can vary the timing of transformation in relation to growth opportunity or mortality risk in the larval habitat. They do this by modulating the production of thyroid hormone (TH), the primary inducer of metamorphosis, and CORT, which synergizes with TH to promote tissue transformation. Hypophysiotropic neurons that release the stress neurohormone corticotropin-releasing factor (CRF) are activated in response to environmental stress (e.g., pond drying, food restriction, etc.), and CRF accelerates metamorphosis by directly inducing secretion of pituitary thyrotropin and corticotropin, thereby increasing secretion of TH and CORT. Although activation of the neuroendocrine stress axis promotes immediate survival in a deteriorating larval habitat, costs may be incurred such as reduced tadpole growth and size at metamorphosis. Small size at transformation can impair performance of the adult, reducing probability of survival in the terrestrial habitat, or fecundity. Furthermore, elevations in CORT in the tadpole caused by environmental stressors cause long term, stable changes in neuroendocrine function, behavior and physiology of the adult, which can affect fitness. Comparative studies show that the roles of stress hormones in developmental plasticity are conserved across vertebrate taxa including humans.

Stress reactivity near birth affects nest building timing and offspring number and survival in the European rabbit (Oryctolagus cuniculus).

The physiological response to stressors has great importance, and its variance has an adaptive role in the survival of individuals. This study describes the effects of stress-axis activation on maternal behavior during the birthing process (parturition) in captive rabbits (Oryctolagus cuniculus). In this species, chances of survival are strongly influenced by nest quality. Thus, maternal care is initiated with nest preparation in late pregnancy, which itself is subject to strict and complex hormonal regulation. Among these hormones, progesterone is one of the most dominant in the process of nest construction. We have demonstrated that its level is altered by the level of cortisol elevation in the animal in question, potentially having an influence on the preparation of the nest for the newborn kittens. We found that does that had a constant and un-elevated level of cortisol metabolite while delivering their litters performed better than those individuals that showed an increased corticoid response around parturition. The latter group exhibited a perceptible delay in the building of their nests, and in addition, further losses were also experienced in their already smaller litters. As the quality of the nest itself proved to be was in no way inferior to those of the other group, this higher kitten-mortality rate may be attributed to impaired maternal behavior. Individual variances in cortisol levels may also result in subtle changes in hormonal regulation, potentially affecting the expression of maternal behavior. We have concluded that the higher level of cortisol detected in more-sensitive does effectively disrupts the natural hormonal regulation involved in their nest-building processes.

Zygotic exposure to venlafaxine disrupts cortisol stress axis activity in multiple generations of zebrafish.

Ubiquitous use of antidepressants has resulted in increased concentrations of these pharmaceuticals in waterways receiving municipal wastewater effluent. Amongst these, venlafaxine, a selective serotonin and norepinephrine reuptake inhibitor, is commonly found at concentrations surpassing 1ppb in surface waters. We recently showed that the deposition of venlafaxine in zebrafish (Danio rerio) embryos impacts neural development in the hypothalamus, suggesting the possibility of neuroendocrine disruptions due to this antidepressant. Here, we tested the hypothesis that early developmental exposure to venlafaxine disrupts the long-term functioning of the hypothalamus-pituitary-interrenal (HPI) axis in zebrafish. Embryos (1-4cell stage) were injected with either 0, 1, or 10ng venlafaxine, and the ontogeny of cortisol content, as well as changes in cortisol levels following a stressor in larvae and adults were assessed across 3 generations. Zygotic venlafaxine exposure did not affect the ontogeny of cortisol production, but there was a disruption in the cortisol response to stressor exposure, which was also evident in multiple generations. In the F0 generation, venlafaxine exposure did not affect cortisol levels in response to stressor exposure in larvae, but adult females, and not males, showed an attenuated cortisol response compared to control fish. This reduction in cortisol levels in the females was rescued by stimulation with adrenocorticotropic hormone, suggesting that the disruption was at the level of the hypothalamus-pituitary axis. Venlafaxine-mediated disruption in HPI axis functioning was also evident in the F1 and F2 generations, including impaired cortisol responses to a stressor in adult female and larval fish, respectively. Taken together, our results suggest that venlafaxine is an endocrine disruptor, and early developmental exposure to this antidepressant may have long-term and generational consequences on cortisol stress axis activity in zebrafish.

Altered metabolic and hormonal responses to moderate exercise in overweight/obesity

BackgroundAn adequate metabolic and hormonal response to the switch from rest to exercise is critical for the health benefits of exercise interventions. Previous work suggests that this response is impaired with overweight/obesity but the specific differences between overweight/obese and lean individuals remain unclear. MethodsWe compared glucose and non-esterified fatty acid (NEFA) regulation and the changes of key homeostatic hormones during 45 min of moderate exercise between 17 overweight/obese and 28 lean premenopausal women. For this comparison, we implemented an exercise protocol at 60% of individual peak oxygen uptake, with frequent blood sampling and under fasting conditions. ResultsWe found that at the same exercise intensity in the overweight/obese and the lean group of women, the metabolic and hormonal response differed. In contrast to the lean group, the overweight/obese group portrayed an activation in the stress axis (adrenocorticotropic hormone (ACTH)/cortisol) and a lower growth hormone (hGH) response and exercise-increase of plasma NEFA. Both groups, however, displayed increased insulin sensitivity during exercise that was accompanied by a normalization of the elevated fasting glucose in the overweight/obese group after 15–20 min. ConclusionWe conclude that the response to exercise in overweight/obese subjects indeed differs from that in lean individuals. Additionally, we demonstrate that exercise can elicit beneficial (improved glucose regulation) and unwanted effects (stress axis activation) in overweight/obese subjects at the same time. This second finding suggests that exercise interventions for overweight/obese subjects need careful consideration of intensity and dose in order to achieve the intended results and avoid acute, undesired reactions.

Sex-dependent effects of paternal deprivation and chronic variable stress on novel object recognition in adult California mice (Peromyscus californicus)

Early-life stress exposure can confer vulnerability for development of psychiatric illnesses and impaired cognition in adulthood. It is well-known that early-life stress can dysregulate the hypothalamic-pituitary-adrenal (HPA) axis in a sex-dependent manner. Specifically, uniparental rodent models of prolonged disrupted mother-offspring relationships (e.g., maternal separation) have demonstrated greater alterations in stress responsivity in adult males, compared to females. Also, chronic early-life stressors (e.g., limited bedding model) impair cognitive function in males more than females. However, the sex-dependent effects of early-life stress and later-life chronic HPA axis activation on cognition have not been well-characterized. Here, we utilized the biparental California mouse (Peromyscus californicus) to model the early-life adversity of paternal deprivation (PD). Fathers either remained in the nest (biparental care) or were permanently removed (PD) on postnatal day (PND) 1. Adult offspring were exposed to daily handling (control) or chronic variable stress (CVS; three stressors for seven days). Twenty-four hours after the final stressor, the novel object recognition (NOR) task commenced, followed by serum collection for corticosterone (CORT) analysis. Independent of sex or rearing, CVS increased CORT. Exploration during acquisition for the NOR task was increased as a result of CVS and PD. During NOR testing, non-stressed females exhibited greater difference scores (i.e., increased recognition memory), compared to non-stressed males. However, the addition of CVS diminished difference scores in females – an effect not observed in CVS-exposed males. Overall, these data suggest that neonatal paternal experience, sex, and chronic stress contribute to exploratory behavior, cognition, and stress hormone concentrations in a biparental species.

Exposure to hypoxia inhibits pituitary-testicular activity in the fish Oreochromis mossambicus

Fishes are exposed to natural hypoxic conditions during aquacultural practices. Although negative effects of hypoxia are documented on fish reproduction, the mechanism of hypoxia-induced alteration in spermatogenic process is not well understood in continuously breeding fishes. The aim of this investigation was to determine the influence of hypoxia on pituitary-testicular activity in the tilapia Oreochromis mossambicus, a cichlid fish that breeds throughout the year. The fish were exposed to moderate hypoxia (MH, Dissolved oxygen (DO) level, 3.24 ± 0.22 mg/L) and severe hypoxia (SH, DO level, 1.64 ± 0.38 mg/L) for 21 days. No significant differences were noticed in the mean numbers of spermatogonia (Sg), primary spermatocytes (Ps), secondary spermatocytes (Ss), early spermatids (Est) and late spermatids (Lst) between controls and fish subjected to MH, whereas the numbers of these cells were significantly lower in fish exposed to SH. Furthermore, weakly immunoreactive luteinizing hormone (LH) secreting cells in the proximal pars distalis (PPD) of the pituitary gland were concomitant with significant reduction in mean serum levels of LH and testosterone as well as androgen receptor immunoreactivity in the Sertoli cells in the testis of fish exposed to SH compared to other groups. On the other hand, the serum cortisol levels were significantly higher in fish exposed to SH compared with other experimental groups. Taken together, these results indicate that the tilapia is able to withstand the moderate hypoxic condition, whereas exposure to severe hypoxic condition suppresses the process of spermatogenesis through the inhibition of LH secretion, which in turn might suppress the testicular steroidogenesis and androgen receptor expression in the Sertoli cells. The results also suggest a possibility that this inhibition might be mediated through the activation of stress-axis in O. mossambicus.