Circulating Corticosterone Concentrations Research Articles

Chronic Adolescent Restraint Stress Downregulates miRNA-200a Expression in Male and Female C57BL/6J and BALB/cJ Mice.

Adolescence is a critical developmental period when the brain is plastic, and stress exposure can have lasting physiological consequences. One mechanism through which adolescent stress may have lasting effects is by altering microRNAs (miRNAs), leading to wide-scale gene expression changes. Three prior independent studies used unbiased approaches (RNA sequencing or microarray) to identify miRNAs differentially expressed by chronic variable stress in male rodents. In all three studies, miRNA-200a was differentially expressed in areas of the brain associated with emotion regulation. The current study extends this research to determine if chronic non-variable adolescent stress downregulates miRNA-200a expression by looking at two strains (BALB/cJ and C57BL/6J) of male and female mice. We utilized a 14-day (2 h/day) restraint stress protocol and verified stress effects on adolescent body weight gain and circulating corticosterone concentrations relative to non-restraint controls. Mice were then left undisturbed until they were euthanized in adulthood, at which time brains were collected to measure miRNA-200a in the ventral hippocampus. Three weeks after adolescent stress ended, differences in body weight between groups were no longer significant; however, animals exposed to stress had less miRNA-200a expression in the ventral hippocampus than control animals. These data implicate miRNA-200a expression as a potential mechanism by which adolescent stress can have persistent impacts on multiple outcomes in both male and female mice.

Nutrient-sensing AgRP neurons relay control of liver autophagy during energy deprivation

Autophagy represents a key regulator of aging and metabolism in sensing energy deprivation. We find that fasting in mice activates autophagy in the liver paralleled by activation of hypothalamic AgRP neurons. Optogenetic and chemogenetic activation of AgRP neurons induces autophagy, alters phosphorylation of autophagy regulators, and promotes ketogenesis. AgRP neuron-dependent induction of liver autophagy relies on NPY release in the paraventricular nucleus of the hypothalamus (PVH) via presynaptic inhibition of NPY1R-expressing neurons to activate PVHCRH neurons. Conversely, inhibiting AgRP neurons during energy deprivation abrogates induction of hepatic autophagy and rewiring of metabolism. AgRP neuron activation increases circulating corticosterone concentrations, and reduction of hepatic glucocorticoid receptor expression attenuates AgRP neuron-dependent activation of hepatic autophagy. Collectively, our study reveals a fundamental regulatory principle of liver autophagy in control of metabolic adaptation during nutrient deprivation.

Paternal deprivation induces vigilance-avoidant behavior and accompanies sex-specific alterations in stress reactivity and central proinflammatory cytokine response in California mice (Peromyscus californicus).

Early-life stress (ELS) can increase anxiety, reduce prosocial behaviors, and impair brain regions that facilitate emotional and social development. This knowledge greatly stems from assessing disrupted mother-child relationships, while studies investigating the long-term effects of father-child relationships on behavioral development in children are scarce. However, available evidence suggests that fathers may uniquely influence a child's behavioral development in a sex-specific manner. Rodent models examining mother-offspring interaction demonstrate relationships among ELS, neuroinflammatory mediators, and behavioral development; yet, the role paternal care may play in neuroimmune functioning remains unreported. Using the biparental California mouse (Peromyscus californicus), we examined to what extent paternal deprivation impairs social and anxiety-like behaviors, augments peripheral corticosterone (CORT) response, and alters central proinflammatory cytokine production following an acute stressor in adulthood. Biparentally reared and paternally deprived (permanent removal of the sire 24h post-birth) adult mice were assessed for sociability, preference for social novelty, social vigilance, and social avoidance behaviors, followed by novelty-suppressed feeding (NSF) testing for general anxiety-like behavior. Following an acute stressor, circulating CORT concentrations and region-specific proinflammatory cytokine concentrations were determined via radioimmunoassay and Luminex multianalyte analysis, respectively. In response to a novel same-sex conspecific, social vigilance behavior was associated with reduced sociability and increased avoidance in paternally deprived mice-an effect not observed in biparentally reared counterparts. Yet, in response to a familiar same-sex conspecific, social vigilance persisted but only in paternally deprived females. The latency to consume during NSF testing was not significantly altered by paternal deprivation. In response to an acute physical stressor, lower circulating CORT concentrations were observed in paternally deprived females. Compared to control-reared males, paternal deprivation increased hypothalamic interleukin-1β, but decreased hippocampal IL-6 protein concentration. Greater social vigilance behavior was demonstrated in paternally deprived mice while they avoided social interaction with a novel same-sex conspecific; however, in response to a familiar same-sex conspecific, paternal deprivation increased social vigilance behavior but only in females. It is possible that different neurobiological mechanisms underlie these observed behavioral outcomes as sex-specific central proinflammatory cytokine and stress responsivity were observed in paternally deprived offspring.

The cortisol switch between vulnerability and resilience.

In concert with neuropeptides and transmitters, the end products of the hypothalamus-pituitary-adrenal (HPA) axis, the glucocorticoid hormones cortisol and corticosterone (CORT), promote resilience: i.e., the ability to cope with threats, adversity, and trauma. To exert this protective action, CORT activates mineralocorticoid receptors (MR) and glucocorticoid receptors (GR) that operate in a complementary manner -as an on/off switch- to coordinate circadian events, stress-coping, and adaptation. The evolutionary older limbic MR facilitates contextual memory retrieval and supports an on-switch in the selection of stress-coping styles at a low cost. The rise in circulating CORT concentration after stress subsequently activates a GR-mediated off-switch underlying recovery of homeostasis by providing the energy for restraining the primary stress reactions and promoting cognitive control over emotional reactivity. GR activation facilitates contextual memory storage of the experience to enable future stress-coping. Such complementary MR-GR-mediated actions involve rapid non-genomic and slower gene-mediated mechanisms; they are time-dependent, conditional, and sexually dimorphic, and depend on genetic background and prior experience. If coping fails, GR activation impairs cognitive control and promotes emotional arousal which eventually may compromise resilience. Such breakdown of resilience involves a transition to a chronic stress construct, where information processing is crashed; it leads to an imbalanced MR-GR switch and hence increased vulnerability. Novel MR-GR modulators are becoming available that may reset a dysregulated stress response system to reinstate the cognitive flexibility required for resilience.

Inferring Whole-Organism Metabolic Rate From Red Blood Cells in Birds.

Metabolic rate is a key ecological variable that quantifies the energy expenditure needed to fuel almost all biological processes in an organism. Metabolic rates are typically measured at the whole-organism level (woMR) with protocols that can elicit stress responses due to handling and confinement, potentially biasing resulting data. Improved, non-stressful methodology would be especially valuable for measures of field metabolic rate, which quantifies the energy expenditure of free-living individuals. Recently, techniques to measure cellular metabolic rate (cMR) in mitochondria of blood cells have become available, suggesting that blood-based cMR can be a proxy of organismal aerobic performance. Aerobic metabolism actually takes place in the mitochondria. Quantifying cMR from blood samples offers several advantages such as direct estimates of metabolism and minimized disturbance of individuals. To our knowledge, the hypothesis that blood-based cMR correlates with woMR has not yet been directly tested. We measured cMR in red blood cells of captive great tits (Parus major), first during their morning activity period and second after subjecting them to a 2.5 h day-time respirometry protocol to quantify woMR. We predicted cMR to decrease as individuals transitioned from an active to a resting state. In the two blood samples we also assessed circulating corticosterone concentrations to determine the perceived disturbance of individuals. From respirometry traces we extracted initial and final woMR measures to test for a predicted positive correlation with cMR measures, while accounting for corticosterone concentrations. Indeed, cMR declined from the first to the second measurement. Furthermore, woMR and cMR were positively related in individuals that had relatively low corticosterone concentrations and displayed little locomotor activity throughout respirometry. By contrast, woMR and cMR covaried negatively in birds that increased corticosterone concentrations and activity levels substantially. Our results show that red blood cell cMR represents a proxy for woMR when birds do not display signs of stress, i.e., either before increases in hormonal or behavioral parameters have occurred or after they have abated. This method represents a valuable tool for obtaining metabolic data repeatedly and in free-living individuals. Our findings also highlight the importance of accounting for individual stress responses when measuring metabolic rate at any level.

Telomere shortening is associated with corticosterone stress response in adult barn swallows.

When vertebrates face stressful events, the hypothalamic–pituitary–adrenal (HPA) axis is activated, generating a rapid increase in circulating glucocorticoid (GC) stress hormones followed by a return to baseline levels. However, repeated activation of HPA axis may lead to increase in oxidative stress. One target of oxidative stress is telomeres, nucleoprotein complexes at the end of chromosomes that shorten at each cell division. The susceptibility of telomeres to oxidizing molecules has led to the hypothesis that increased GC levels boost telomere shortening, but studies on this link are scanty. We studied if, in barn swallows Hirundo rustica, changes in adult erythrocyte telomere length between 2 consecutive breeding seasons are related to corticosterone (CORT) (the main avian GC) stress response induced by a standard capture-restraint protocol. Within-individual telomere length did not significantly change between consecutive breeding seasons. Second-year individuals showed the highest increase in circulating CORT concentrations following restraint. Moreover, we found a decline in female stress response along the breeding season. In addition, telomere shortening covaried with the stress response: a delayed activation of the negative feedback loop terminating the stress response was associated with greater telomere attrition. Hence, among-individual variation in stress response may affect telomere dynamics.

SAT-586 Cold-Acclimation Prevents the Onset of Glucocorticoid-Induced Adipose Dysfunction in Male Mice

Glucocorticoid (GC) excess, either endogenously or exogenously, has been causally linked to the development of chronic diseases such as obesity and type-2 diabetes mellitus. Continuously elevated GC levels result in an expansion of white adipose tissue (WAT) depots and a dramatic decrease in the thermogenic capacity in brown and beige adipose tissue (BAT and BeAT, respectively). Herein we aimed to examine the interaction between GCs and the sympathetic nervous system (SNS) in the regulation of WAT, BAT, and BeAT. To this end, we utilized an altered environmental temperature as a non-invasive method for the modulation of sympathetic activity - cold is an activator of SNS-mediated non-shivering thermogenesis. Thus, during a 4-week treatment with either corticosterone or placebo, 10-week-old male C57BL/6NRj mice were maintained at two different temperature levels: 29°C (thermoneutrality) or 13°C (cold temperature). Body weight, as well as energy and water intake, were monitored throughout the study. At sacrifice, serum and adipose tissues were collected for analysis. GC-exposed mice showed a marked increase in circulating corticosterone concentrations compared to placebo controls with no appreciable difference between temperature levels. At thermoneutrality, GC-treated mice gained more weight and consumed more food than their placebo-treated littermates. This GC-induced body weight gain was accompanied by increased (visceral & subcutaneous) WAT weight as well as adipocyte hypertrophy. Interestingly, cold-acclimatized mice showed a marked reduction in GC-induced weight gain, hyperphagia, and fat accumulation. Moreover, the GC-induced rise in blood glucose and serum insulin concentrations - readily observed when mice were maintained at thermoneutrality - was absent in cold-exposed animals. In addition, GC treatment at thermoneutrality resulted in increased lipid deposition and decreased UCP1 expression in BAT, the ‘whitening’ of BAT. This GC-induced loss of thermogenic capacity was profoundly reduced in cold-adapted mice. Across all groups, UCP-1 protein levels in BAT closely correlated (r2 = 0.70, p < 0.0001) with those of tyrosine hydroxylase (TH), the rate-limiting enzyme of catecholamine synthesis. These results indicate that cold-acclimation prevents the development of GC-induced metabolic dysfunction in mice. Thus, environmental temperature is a potent modulator of GC-induced adiposity and body weight gain, potentially via an interaction between SNS and GC signaling.

Food supplementation by an invasive fleshy-fruited shrub sustains body condition of a native frugivorous bird during winter.

Birds tend to adjust their behavior and physiology to changes in food availability in their environment. Seasonal fluctuation of food resources may act as an energetic challenge, augmenting hypothalamus-pituitary-adrenal axis (HPA axis) activity, leading to an increase in corticosterone concentrations and promoting the metabolism of energy stores. Plant invasions may alter seasonal food fluctuations by providing a food supply during scarce seasons. This could attenuate the energetic challenge, reducing HPA axis activity and the metabolism of reserves. Using a system with seasonal fluctuation in food availability, we tested if fruit supplementation by the invasive fleshy-fruited Pyracantha angustifolia during the season of native fruit scarcity decreases the consumption of energy stores through activity attenuation of the HPA axis. We measured changes in body condition and circulating corticosterone (CORT) concentration in Turdus chiguanco occurring at sites both invaded and not invaded by P. angustifolia over 3 time periods that correspond to the periods prior to, during and after highest fruit production of the plant. Fruit scarcity in the ecosystem appears as an energetic challenge for T. chiguanco, given that body mass, fat score and residuals of body mass/tarsus length decreased during winter in a site not invaded by the exotic shrub. Conversely, the presence of the invasive plant seemed to attenuate the metabolism of energetic reserves, as we did not record changes in body condition in birds inhabiting the invaded site. Unexpectedly, plasma CORT concentration did not vary between sites or periods. Further evaluation is required to elucidate how enhanced body condition, resulting from the consumption of a fleshy-fruited invasive plant, affects survivorship and reproductive performance in T. chiguanco.

Baclofen but Not Diazepam Alleviates Alcohol-Seeking Behavior and Hypothalamic-Pituitary-Adrenal Axis Dysfunction in Stressed Withdrawn Mice.

This study compares the impact of repeated injections of baclofen (an agonist of GABAB receptors) or diazepam (a benzodiazepine having an agonist action on GABAA receptors) given during the alcohol-withdrawal period on the stress-induced restoration of alcohol-seeking behavior and hypothalamic–pituitary–adrenal (HPA) axis dysfunction after a long (4 weeks) abstinence. Thus, C57BL/6 mice were submitted to a 6-month alcohol consumption [12% volume/volume (v/v)] and were progressively withdrawn to water before testing. Diazepam (Valium®, Roche) and baclofen (Baclofen®, Mylan) were administered intraperitoneally for 15 consecutive days (1 injection/day) during the withdrawal period at decreasing doses ranging from 1.0 mg/kg (Day 15) to 0.25 mg/kg (Day 1) for diazepam and from 1.5 mg/kg (Day 15) to 0.37 mg/kg (Day 1) for baclofen. Alcohol-seeking behavior was evaluated by alcohol-place preference in an odor recognition task. In the stress condition, mice received three electric footshocks 45 min before behavioral testing. Blood was sampled immediately after behavioral testing, and plasma corticosterone concentrations were measured by commercial enzyme immunoassay kits. Results showed that non-stressed withdrawn mice did not exhibit alcohol-place preference or alteration of plasma corticosterone concentrations relative to water controls. After stress, however, withdrawn mice exhibited a significant alcohol-place preference and higher circulating corticosterone concentrations as compared to stressed water controls. Interestingly, repeated administration during the withdrawal phase of baclofen but not diazepam suppressed both the alcohol-place preference and normalized corticosterone levels in stressed withdrawn animals. In conclusion, this study evidences that a pre-treatment with baclofen but not with diazepam during the withdrawal phase normalized, even after a long period of abstinence, the HPA axis response to stress, which contributes to the long-term preventing effects of this compound on alcohol-seeking behavior.

Grading Distress of Different Animal Models for Gastrointestinal Diseases Based on Plasma Corticosterone Kinetics.

Simple SummaryAnimal welfare is an important aspect of biomedical research. Many regulations have been implemented to combine high quality of research with minimal harm to laboratory animals. These guidelines also demand a prospective severity assessment of each animal model. A comparison of distress between animal models could allow realistic harm and benefit analysis and an appropriate use of refinement methods. However, studies comparing distress between different animal models are still rare. One good parameter for analyzing distress is the concentration of the stress hormone corticosterone in the blood. Therefore, we compared the corticosterone kinetics of distinct gastrointestinal animal models. The aim of this study was to evaluate which parameter the highest corticosterone concentration or the duration of increased stress hormone level could be used to quantify distress. We observed a significant increase of corticosterone 30 min after stress induction in all animal models. However, the corticosterone kinetics differed between the distinct interventions. Both the absolute value and the duration of increased corticosterone level correlated directly with an assessed distress score. We conclude that both variables of corticosterone kinetics are valid parameters to compare distress between animal models. Comparative studies for evaluating distress in established animal models are still rare. However, this issue is becoming more important as a consequence of worldwide appreciation of animal welfare. One good parameter for evaluating distress is the quantification of corticosterone. We hypothesized that not just the absolute value but also the duration of increased corticosterone concentration in the blood is an important aspect for evaluating animal distress. Therefore, we analyzed plasma corticosterone concentrations 30, 60, 120, and 240 min after induction of pancreatitis by cerulein, liver damage by carbon tetrachloride, liver damage by bile duct ligation, and after orthotopic injection of pancreatic cancer cells. We also evaluated corticosterone kinetics after injection of distinct carrier substances. Compared to phosphate buffered saline, dimethyl sulfoxide leads to dose-dependent higher and longer-lasting circulating corticosterone concentrations. In all disease models, we observed significantly increased corticosterone concentration 30 min after stress induction. However, the corticosterone kinetics differed among the animal models. Both the absolute value of corticosterone concentration and the duration correlated positively with the quantification of animal distress by a score sheet. This suggests that both variables of corticosterone kinetics might provide a solid basis for comparing and grading distress of different animal models.

Non-invasive monitoring of physiological stress in an afrotropical arid-zone passerine bird, the southern pied babbler

Using faecal matter to monitor stress levels in animals non-invasively is a powerful technique for elucidating the effects of biotic and abiotic stressors on free-living animals. To validate the use of droppings for measuring stress in southern pied babblers (Turdoides bicolor) we performed an ACTH challenge on captive individuals and determined the effect of temporary separation from their social group on their faecal glucocorticoid metabolite (fGCM) concentration. Additionally, we compared fGCM concentrations of captive babblers to those of wild conspecifics and examined the effects of dominance rank on fGCM concentration. We found droppings to be a suitable matrix for measuring physiological stress in babblers and that individual separation from the group caused an increase in fGCM levels. In addition, babblers temporarily held in captivity had substantially higher fGCM concentrations than wild individuals, indicating that babblers kept in captivity experience high levels of stress. In wild, free-living individuals, dominant males showed the highest levels of stress, suggesting that being the dominant male of a highly territorial social group is stressful. Non-invasive sampling allows field-based researchers to reduce disturbance related to monitoring adrenocortical function, thereby avoiding artificially increasing circulating corticosterone concentration as it is not necessary to physically restrain study animals.

Influence of corticosterone on growth, home-cage activity, wheel running, and aerobic capacity in house mice selectively bred for high voluntary wheel-running behavior

Glucocorticoids, a class of metabolic hormones, impact a wide range of traits (e.g., behavior, skeletal growth, muscle maintenance, glucose metabolism), and variation in concentrations of circulating glucocorticoids (such as corticosterone), at the level of natural individual variation, in relation to endocrine disorders, or from exogenous supplementation, have manifold effects. Changes in circulating corticosterone concentrations can also impact multiple aspects of locomotor behavior, including both motivation and physical ability for exercise. To examine further the role of corticosterone in locomotor behavior and associated traits, we utilized laboratory house mice from a long-term experiment that selectively breeds for high levels of voluntary exercise. As compared with four non-selected control (C) lines, mice from the four replicate High Runner (HR) lines have ~2-fold higher baseline circulating corticosterone concentrations as well as ~3-fold higher voluntary wheel running on a daily basis, higher home-cage activity when deprived of wheels, higher maximal aerobic capacity, and smaller body size; potentially, all of these differences could be modulated by circulating corticosterone. We administered 50 μg/mL corticosterone-21-hemisuccinate in the drinking water of both HR and C male mice from weaning through ~8 weeks of age. As compared with mice from C lines, HR mice had higher endogenous corticosterone levels; higher daily wheel-running distance, duration, and speed; higher maximal oxygen consumption during forced exercise (VO2max); spent more time in the closed arms of an elevated plus maze; and had larger reproductive fat pads. For both HR and C mice, corticosterone treatment strongly suppressed endogenous circulating corticosterone levels, decreased growth rate and adult body mass, increased food and water consumption (both adjusted for body mass), increased entries into closed arms of an elevated plus maze, decreased home-cage activity (total and average intensity), decreased wheel-running distance and maximum speed, and decreased VO2max. At the suborganismal level, corticosterone treatment decreased relative adrenal, liver, and triceps surae muscle mass, as well as tail length, but increased both subdermal and reproductive fat pad masses, as well as hematocrit. Overall, the responses of both HR and C mice to corticosterone supplementation were “negative” from a health perspective. These results have significant implications for understanding both the evolution of baseline corticosterone levels and stress-related effects on activity levels. They also suggest that patients experiencing extended periods of glucocorticoid treatment might benefit from attempts to increase their physical activity as an adjuvant.

Sex differences in hippocampal mineralocorticoid and glucocorticoid receptor mRNA expression in response to acute mate pair separation in zebra finches (Taeniopygia guttata).

Mate separation has been shown to mediate changes in physiological and behavioral processes via activation of the hypothalamo-pituitary-adrenal (HPA) axis in both mammalian and avian species. To elucidate the neural mechanisms associated with changes in the HPA axis in response to social stress, we investigated the effects of mate pair separation on circulating corticosterone concentrations as well as gene expression levels of mineralocorticoid receptor (MR), glucocorticoid receptor (GR), and corticotropin releasing hormone (CRH) in the hypothalamus and hippocampus of both male and female zebra finches, a species that forms strong pair bonds. Zebra finches (Taeniopygia guttata) were housed three to a cage (a mated pair plus a stimulus female), and were assigned to one of three new housing treatment groups: (1) male or female removed from their respective mate and placed in a cage with a new opposite sex conspecific and stimulus female (2) male or female that remained with their mate, but a new stimulus female was introduced, or (3) the subjects were handled but not separated from their mate or the stimulus female. After 48 hr in the new housing condition, we observed significant increases in plasma corticosterone concentrations in response to both mate pair and stimulus female separation. No significant differences in MR, GR, or CRH mRNA expression in the hypothalamus were observed in response to any treatment for both males and females. Females exhibited a significant up regulation in hippocampal MR, but not GR mRNA, whereas males exhibited a significant down regulation of both hippocampal MR and GR mRNA in response to mate pair separation. Thus, the hippocampus appears to play a key role in regulating sex specific responses to social stressors.

House sparrows mitigate growth effects of post-natal glucocorticoid exposure at the expense of longevity

Acute, short-term effects of early-life stress and associated glucocorticoid upregulation on physiology and survival are widely documented across vertebrates. However, the persistence and severity of these effects are largely unknown, especially through the adult stage and for natural systems. Here, we investigate physiological, morphological, and survival effects of post-natal glucocorticoid upregulation across the nestling, juvenile, and adult life stages in house sparrows (Passer domesticus). We manipulate circulating corticosterone concentration in wild, free-living house sparrow nestlings and monitor body size, size-corrected mass, two measures of health (hematocrit and phytohemagglutinin-induced skin swelling), and survival in a captive environment until adulthood. We find that early-life corticosterone exposure depresses nestling size-corrected mass in both sexes, with no strong effect of the treatment on body size or our two measures of health. Birds are able to compensate for negative effects of high early-life corticosterone exposure in the long-term and this effect largely disappears by the juvenile and adult stages. However, treatment has a negative effect on survival through one year of age, suggesting that long-term compensation comes at a price.

Beneficial metabolic effects of dietary epigallocatechin gallate alone and in combination with exendin-4 in high fat diabetic mice

ObjectiveSignificant attempts are being made to generate multifunctional, hybrid or peptide combinations as novel therapeutic strategies for type 2 diabetes, however this presents key challenges including design and pharmaceutical development. In this study, we evaluated metabolic properties of oral nutritional supplement epigallocatechin gallate (EGCG) in combination with GLP-1 agonist exendin-4 in a mouse model of dietary-induced diabetes and obesity. MethodsEGCG, exendin-4 or combination of both were administered twice-daily over 28 days to high fat (HF) mice on background of low-dose streptozotocin. Energy intake, body weight, fat mass, glucose tolerance, insulin sensitivity, lipid profile, biochemical and hormone markers, and islet histology were examined. ResultsAll treatment groups exhibited significantly reduced body weight, fat mass, circulating glucose and insulin concentrations, and HbA1c levels which were independent of changes in energy intake. Similarly, there was marked improvement in glycaemic control, glucose-stimulated insulin release, insulin sensitivity, total cholesterol and triglycerides, with most prominent effects observed following combination therapy. Circulating corticosterone concentrations and 11beta-hydroxysteroid dehydrogenase type1 (11β-HSD1) staining (in pancreas) were beneficially decreased without changes in circulating interleukin 6 (IL-6), alanine transaminase (ALT) and glutathione reductase. Combination therapy resulted in increased islet area and number, beta cell area, and pancreatic insulin content. Generally, metabolic effects were much more pronounced in mice which received combination therapy. ConclusionsEGCG alone and particularly in combination with exendin-4 exerts positive metabolic properties in HF mice. EGCG may be useful dietary adjunct alongside GLP-1 mimetics in treatment of diabetes and related disorders.

Developmental corticosterone treatment does not program immune responses in zebra finches (Taeniopygia guttata).

Developmental conditions may impact the expression of immune traits throughout an individual's life. Early-life challenges may lead to immunological constraints that are mediated by endocrine-immune interactions. In particular, individual differences in the ability to mount immune responses may be programmed by exposure to stressors or glucocorticoid hormones during development. To test this hypothesis, we experimentally elevated levels of the glucocorticoid hormone corticosterone during the nestling and fledgling periods in captive zebra finches (Taeniopygia guttata). We subsequently challenged birds with the antigen lipopolysaccharide (LPS) on days 60 and 100 post-hatch to determine if developmental exposure to elevated corticosterone impacted the later response to LPS. As measures of immune function, we quantified bacteria killing ability, haptoglobin concentrations, and LPS-specific antibody responses at multiple time points. We also measured circulating corticosterone concentrations during the experimental period and on day 60 before and after endotoxin challenge. During the experimental period, corticosterone treatment elevated corticosterone levels. Corticosterone treatment did not induce programming effects on immune function or corticosterone production. Independent of treatment, individuals with higher corticosterone concentrations during the nestling period had lower bacteria killing ability on day 36 and higher baseline corticosterone concentrations on day 60 post-hatch. These results suggest a limited role for corticosterone exposure during early life to mediate immunological constraints later in life. Manipulation of cortisol may be necessary to conclusively determine if developmental glucocorticoid exposure can program immune function in birds. To determine if developmental stress can program the immune response, exposure to environmentally relevant stressors should also be manipulated.

Delayed effect of early-life corticosterone treatment on adult anti-predator behavior in a common passerine

Acute, short-term effects of early-life stress and associated glucocorticoid upregulation on behavior are widely documented across vertebrates. However, the persistence and severity of these effects are largely unknown, especially through the adult stage and in wild species. Here, we investigate long-term effects of experimental post-natal increases in a circulating glucocorticoid on antipredator behavior in wild house sparrows (Passer domesticus) tested in captivity. We manipulate circulating corticosterone concentration in wild, free-living nestlings, transfer fledglings to captivity, and test juveniles and adults for two measures of antipredator behavior: evasiveness during a direct human encounter, and propensity to escape from a risky environment. We find no effect of early-life stress hormone manipulation on escape behavior, but a delayed effect on evasive behavior: evasive behavior was depressed in adults but not juveniles, and influenced by current body condition. These results highlight the importance of state-behavior interactions and life stage in assessing long-term effects of early-life stress, and provide rare evidence for delayed effects of early-life stress to adults of a wild avian species.

Stress hormone levels in a freshwater turtle from sites differing in human activity.

Glucocorticoids, such as corticosterone (CORT), commonly serve as a measure of stress levels in vertebrate populations. These hormones have been implicated in regulation of feeding behaviour, locomotor activity, body mass, lipid metabolism and other crucial behaviours and physiological processes. Thus, understanding how glucocorticoids fluctuate seasonally and in response to specific stressors can yield insight into organismal health and the overall health of populations. I compared circulating CORT concentrations between two similar populations of painted turtle, Chrysemys picta, which differed primarily in the level of exposure to human recreational activities. I measured basal CORT concentrations as well as the CORT stress response and did not find any substantive difference between the two populations. This similarity may indicate that painted turtles are not stressed by the presence of humans during the nesting season. The results of this study contribute to our understanding of CORT concentrations in freshwater reptiles, a group that is historically under-represented in studies of circulating hormone concentrations; specifically, studies that seek to use circulating concentrations of stress hormones, such as CORT, as a measure of the effect of human activities on wild populations. They also give insight into how these species as a whole may respond to human recreational activities during crucial life-history stages, such as the nesting season. Although there was no discernable difference between circulating CORT concentrations between the urban and rural populations studied, I did find a significant difference in circulating CORT concentrations between male and female C. picta. This important finding provides better understanding of the sex differences between male and female painted turtles and adds to our understanding of this species and other species of freshwater turtle.

Faecal corticosterone metabolite concentrations are not a good predictor of habitat suitability for common gartersnakes.

Measuring habitat suitability is important in conservation and in wildlife management. Measuring the abundance or presence-absence of a species in various habitats is not sufficient to measure habitat suitability because these metrics can be poor predictors of population success. Therefore, having some measure of population success is essential in assessing habitat suitability, but estimating population success is difficult. Identifying suitable proxies for population success could thus be beneficial. We examined whether faecal corticosterone metabolite (fCM) concentrations could be used as a proxy for habitat suitability in common gartersnakes (Thamnophis sirtalis). We conducted a validation study and confirmed that fCM concentrations indeed reflect circulating corticosterone concentrations. We estimated abundance, reproductive output and growth rate of gartersnakes in field and in forest habitat and we also measured fCM concentrations of gartersnakes from these same habitats. Common gartersnakes were more abundant and had higher reproductive outputs and higher growth rates in field habitat than in forest habitat, but fCM concentrations did not differ between the same two habitats. Our results suggest either that fCM concentrations are not a useful metric of habitat suitability in common gartersnakes or that the difference in suitability between the two habitats was too small to induce changes in fCM concentrations. Incorporating fitness metrics in estimates of habitat suitability is important, but these metrics of fitness have to be sensitive enough to vary between habitats.

Corticosterone stress response shows long-term repeatability and links to personality in free-living Nazca boobies

The concept of “coping styles”, or consistently different responses to stressors, is of broad interest in behavioral ecology and biomedicine. Two critical predictions of this concept are individual consistency of neurophysiological and behavioral responses (relative to population variability) and a negative relationship between aggression/proactivity and hypothalamic–pituitary–adrenal axis reactivity. Recent studies failed to provide strong support for these predictions, especially outside of strictly controlled conditions, and long-term measures to test the first prediction are rare. Here, we demonstrate individual repeatability across 2–3years of maximum circulating corticosterone concentration [CORT] and area under the [CORT] response curve (AUCI) during a standard capture-restraint test in wild, free-living adult Nazca boobies (Sula granti). We also show that the stress response predicts the personality traits aggression and anxiety in these birds (measured in the wild); however, the strength of these results was weak. Maximum [CORT] and AUCI showed higher repeatability between years than baseline [CORT]. After controlling breeding status, sex, mass, date sampled, and their interactions, baseline [CORT] was most closely related to personality traits, followed by AUCI, and then maximum [CORT]. The direction of these relationships depended on whether the testing context was social or non-social. [CORT] parameters had little to no relationship with cross-context plasticity in personality traits. Our results generally affirm two critical predictions of coping styles, but match the emerging trend that these relationships are weak in the wild, and may depend on testing context.