Prolonged high secretion of glucocorticoids normally reflects a state of chronic stress, which has been associated with an increase in disease susceptibility and reduction in Darwinian fitness. Here, we hypothesize that an increase in oxidative stress accounts for the detrimental effects of prolonged high secretion of glucocorticoids. We performed a meta-analysis on studies where physiological stress was induced by administration of glucocorticoids to evaluate the magnitude of their effects on oxidative stress. Glucocorticoids have a significant effect on oxidative stress (Pearson r = 0.552), although this effect depends on the duration of treatment, and is larger in long-term experiments. Importantly, there was a significant effect on tissue, with brain and heart being the most and the least susceptible to GC-induced oxidative stress, respectively. Furthermore, effect size was larger (1) in studies using both sexes compared to males only, (2) when corticosterone rather than dexamethasone was administered and (3) in juveniles than in adults. These effects were not confounded by species, biochemical biomarker, or whether wild or laboratory animals were studied. In conclusion, our meta-analysis suggests that GC-induced oxidative stress could be a further mechanism underlying increases in disease susceptibility and decreases in Darwinian fitness observed under chronic stress.

International audienceOur understanding of fundamental organismal biology has been disproportionately influenced by studies of a relatively small number of ‘model’ species extensively studied in captivity. Laboratory populations of model species are commonly subject to a number of forms of past and current selection that may affect experimental outcomes. Here, we examine these processes and their outcomes in one of the most widely used vertebrate species in the laboratory – the zebra finch (Taeniopygia guttata). This important model species is used for research across a broad range of fields, partly due to the ease with which it can be bred in captivity. However despite this perceived amenability, we demonstrate extensive variation in the success with which different laboratories and studies bred their subjects, and overall only 64% of all females that were given the opportunity, bred successfully in the laboratory. We identify and review several environmental, husbandry, life-history and behavioural factors that potentially contribute to this variation. The variation in reproductive success across individuals could lead to biases in experimental outcomes and drive some of the heterogeneity in research outcomes across studies. The zebra finch remains an excellent captive animal system and our aim is to sharpen the insight that future studies of this species can provide, both to our understanding of this species and also with respect to the reproduction of captive animals more widely. We hope to improve systematic reporting methods and that further investigation of the issues we raise will lead both to advances in our fundamental understanding of avian reproduction as well as to improvements in future welfare and experimental efficiency

SUMMARYDevelopmental stress can significantly influence physiology and survival in many species. Mammalian studies suggest that preand post-natal stress can have different effects (i.e. hyper-or hypo-responsiveness) on the hypothalamic-pituitary-adrenal (HPA) axis, the main mediator of the stress response. In mammals, the physiological intimacy between mother and offspring constrains the possibility to control, and therefore manipulate, maternal pre-and post-natal influences. Here, using the Japanese quail (Coturnix coturnix japonica) as our model, we elevated levels of the glucocorticoid stress hormone corticosterone in ovo and/or in the endogenous circulation of hatchlings. We examined the effects of treatments on corticosterone and glucose stress responses at two different ages, in juvenile and adult quail. In juveniles, corticosterone data revealed a sex-specific effect of postnatal treatment regardless of the previous pre-natal protocol, with post-natally treated females showing shorter stress responses in comparison with the other groups, while no differences were observed among males. In adulthood, birds previously stressed as embryos showed higher corticosterone concentrations over the stress response compared with controls. This effect was not evident in birds subjected to either post-natal treatment or the combined treatments. There were no effects on glucose in the juveniles. However, adult birds previously stressed in ovo showed opposite sex-specific basal glucose patterns compared with the other groups. Our results demonstrate that (1) early glucocorticoid exposure can have both transient and long-term effects on the HPA axis, depending upon the developmental stage and sex and (2) post-natal stress can modulate the effects of pre-natal stress on HPA activity.

Repeated exposure to stressful circumstances is generally thought to be associated with increased pathology and reduced longevity. However, growing lines of evidence suggest that the effects of environmental stressors on survival and longevity depend on a multitude of factors and, under some circumstances, might be positive rather than negative. Here, using the zebra finch (Taeniopygia guttata), we show that repeated exposure to stressful conditions (i.e. unpredictable food availability), which induced no changes in body mass, was associated with a decrease in mortality rate and an increase in the age of death. As expected, the treated birds responded to the unpredictable food supply by increasing baseline glucocorticoid stress hormone secretion and there were no signs of habituation of this hormonal response to the treatment across time. Importantly, and consistent with previous literature, the magnitude of hormone increase induced by the treatment was significant, but relatively mild, since the baseline glucocorticoid concentrations in the treated birds were substantially lower than the peak levels that occur during an acute stress response in this species. Taken together, these data demonstrate that protracted exposure to relatively mild stressful circumstances can have beneficial lifespan effects.Key-words. Chronic stress, unpredictable food availability, glucocorticoids, corticosterone, HPA axis, hormesis. IntroductionProtracted or repeated exposure to stressful stimuli, such as those experienced by individuals living in uncontrollable or highly unstable environments, can have wide ranging effects on animal physiology, but the extent to which these effects are adaptive is the subject of considerate debate (Broonstra 2013). In vertebrates, one of the main systems mediating responses to stressful environmental conditions is the Hypothalamic-Pituitary-Adrenal axis (HPA axis), which regulates both basal production and transient surges of circulating glucocorticoid stress hormones. Transient increases in circulating glucocorticoids are a highly conserved component of the vertebrate stress response and play a key role in initiating an array of metabolic changes intended to mobilise energy, including hepatic gluconeogenesis and inhibition of glucose uptake by peripheral tissues . These changes are thought to be vital for promoting short-term survival (Wingfield et al. 1998;Sapolsky 2000). At the same time, dynamic changes in basal level of glucocorticoids, such as those occurring across differing seasons within the same year in a variety of free-living vertebrate species, are also thought to be critical for survival (Romero 2002). Over a longer time scale, however, the repeated activation of the HPA axis may lead to a dysregulation and dysfunction of the stress axis (Sapolsky 2000).The predominant view is that repeated stress exposure, and the consequent prolonged elevation of glucocorticoid levels, is harmful since it can induce a large variety of downstream negative effects, including impairment of brai...

* Joint first authorsHighlights  We exposed zebra finch females to challenging environmental conditions  We examined treatment effects on age-related changes in oxidative stress (OS)  Levels of damage to DNA and proteins increased with chronological age  The treatment produced a higher age-related increase in the level of damage to DNA  We found treatment-specific links among OS and longevity Corresponding author: Pat.Monaghan@glasgow.ac.uk 2 AbstractUnderstanding the links between environmental conditions and longevity remains a major focus in biological research. We examined within-individual changes between early-and midadulthood in the circulating levels of four oxidative stress markers linked to ageing, using zebra finches (Taeniopygia guttata): a DNA damage product (8-hydroxy-2'-deoxyguanosine; 8-OHdG), protein carbonyls (PC), non-enzymatic antioxidant capacity (OXY), and superoxide dismutase activity (SOD). We further examined whether such within-individual changes differed among birds living under control (ad lib food) or more challenging environmental conditions (unpredictable food availability), having previously found that the latter increased corticosterone levels when food was absent but improved survival over a three year period. Our key findings were: (i) 8-OHdG and PC increased with age in both environments, with a higher increase in 8-OHdG in the challenging environment; (ii) SOD increased with age in the controls but not in the challenged birds, while the opposite was true for OXY; (iii) control birds with high levels of 8-OHdG died at a younger age, but this was not the case in challenged birds. Our data clearly show that while exposure to the potentially damaging effects of oxidative stress increases with age, environmental conditions can modulate the pace of this age-related change.