Valeria Marasco

Pre- and post-natal stress in context: effects on the stress physiology in a precocial bird

SUMMARY Developmental stress can significantly influence physiology and survival in many species. Mammalian studies suggest that pre- and 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 post-natal 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.

Developmental post-natal stress can alter the effects of pre-natal stress on the adult redox balance

Across diverse vertebrate taxa, stressful environmental conditions during development can shape phenotypic trajectories of developing individuals, which, while adaptive in the short-term, may impair health and survival in adulthood. Regardless, the long-lasting benefits or costs of early life stress are likely to depend on the conditions experienced across differing stages of development. Here, we used the Japanese quail (Coturnix coturnix japonica) to experimentally manipulate exposure to stress hormones in developing individuals. We tested the hypothesis that interactions occurring between pre- and post-natal developmental periods can induce long-term shifts on the adult oxidant phenotype in non-breeding sexually mature individuals. We showed that early life stress can induce long-term alterations in the basal antioxidant defences. The magnitude of these effects depended upon the timing of glucocorticoid exposure and upon interactions between the pre- and post-natal stressful stimuli. We also found differences among tissues with stronger effects in the erythrocytes than in the brain in which the long-term effects of glucocorticoids on antioxidant biomarkers appeared to be region-specific. Recent experimental work has demonstrated that early life exposure to stress hormones can markedly reduce adult survival (Monaghan et al., 2012). Our results suggest that long-term shifts in basal antioxidant defences might be one of the potential mechanisms driving such accelerated ageing processes and that post-natal interventions during development may be a potential tool to shape the effects induced by pre-natally glucococorticoid-exposed phenotypes.

Repeated exposure to stressful conditions can have beneficial effects on survival.

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.

Pre- and post-natal stress programming : developmental exposure to glucocorticoids causes long-term brain-region specific changes to transcriptome in the precocial Japanese quail

Exposure to stress during early development can permanently influence an individuals physiology and behaviour, and affect its subsequent health. The extent to which elevated glucocorticoids cause such long‐term ‘programming’ remains largely untested. In the present study, using the Japanese quail as our study species, we independently manipulated exposure to corticosterone during pre‐ and/or post‐natal development and investigated the subsequent effects on global gene expression profiles within the hippocampus and hypothalamus upon achieving adulthood. Our results showed that the changes in transcriptome profiles in response to corticosterone exposure clearly differed between the hippocampus and the hypothalamus. We also showed that these effects depended on the developmental timing of exposure and identified brain‐region specific gene expression patterns that were either: (i) similarly altered by corticosterone regardless of the developmental stage in which hormonal exposure occurred or (ii) specifically and uniquely altered by either pre‐natal or post‐natal exposure to corticosterone. Corticosterone‐treated birds showed alterations in networks of genes that included known markers of the programming actions of early‐life adversity (e.g. brain‐derived neurotrophic factor and mineralocorticoid receptor within the hippocampus; corticotrophin‐releasing hormone and serotonin receptors in the hypothalamus). Altogether, for the first time, these findings provide experimental support for the hypothesis that exposure to elevated glucocorticoids during development may be a key hormonal signalling pathway through which the long‐term phenotypic effects associated with early‐life adversity emerge and potentially persist throughout the lifespan. These data also highlight that stressors might have different long‐lasting impacts on the brain transcriptome depending on the developmental stage in which they are experienced; more work is now required to relate these mechanisms to organismal phenotypic differences.

Signaling in a Polluted World: Oxidative Stress as an Overlooked Mechanism Linking Contaminants to Animal Communication

The capacity to communicate effectively with other individuals plays a critical role in the daily life of an individual and can have important fitness consequences. Animals rely on a number of visual and non-visual signals, whose production brings costs to the individual. The theory of honest signaling states that these costs are higher for low than for high-quality individuals, which prevents cheating and makes signals, such as skin and plumage colouration, indicators of individual’s quality or condition. The condition-dependent nature of signals makes them ideally suited as indicators of environmental quality, implying that signal production might be affected by contaminants. In this mini-review article, we have made the point that oxidative stress (OS) is one overlooked mechanism linking exposure to contaminants to signaling because (i) many contaminants can influence the individual’s oxidative balance, and (ii) generation of both visual and non-visual signals is sensitive to oxidative stress. To this end, we have provided the first comprehensive review on the way both non-organic (heavy metals, especially mercury) and organic (persistent organic pollutants) contaminants may influence either OS or sexual signaling. We have also paid special attention to emerging classes of pollutants like brominated flame-retardants and perfluoroalkoxy alkanes in order to stimulate research in this area. We have finally provided suggestions and warnings for future work on the links among OS, sexual signaling and contaminant exposure.

Environmental conditions shape the temporal pattern of investment in reproduction and survival.

The relationship between environmental stress exposure and ageing is likely to vary with stressor severity, life-history stage and the time scale over which effects are measured. Such factors could influence whether stress exposure accelerates or slows the ageing process, but their interactions have not previously been experimentally investigated. We found that experimental exposure of zebra finches to mildly challenging environmental circumstances from young to old adulthood, which increased exposure to stress hormones, reduced breeding performance during early adulthood, but had positive effects when individuals were bred in old adulthood. This difference was not due to selective mortality, because the effects were evident within individuals, and no evidence of habituation in the response to the stressor was found. The more stressful environment had no effects on survival during young or old adulthood, but substantially improved survival during middle age. Changes in the effects at different ages could be due to the duration and nature of the challenging exposure, or to variation in coping capacity or strategy with age. These results show that living under challenging environmental circumstances can influence ageing trajectories in terms of both reproductive performance and longevity. Our results provide experimental support for the emerging idea that stress exposure needs to be optimized rather than minimized to obtain the best health outcomes.

The unsaturated brain: An evolutionary compromise?

Tothe Editor:The brain has ahigh content of polyunsaturated fattyacids (PUFAs), which are critical for neurodevelopment, neuro-transmission, rapid metabolic turnover and repair [Davletov andMontecucco, 2010]. The high susceptibility of PUFAs to peroxida-tion mediated by reactive oxygen species (ROS), however, results inan increased vulnerability of the brain to oxidative damage [Barja,2004]. The production of ROS by mitochondria (e.g. electrontransport chain; alpha-ketoglutarate dehydrogenase in the Krebscycle), peroxisomes or microglia is further exacerbated by the highoxygen consumption of brain [Barja, 2004; Adam-Vizi, 2005].Moreover,theoxidativechallengeforbrainisworsenbytherelativepaucity of antioxidant enzymes compared with other organs.Considering the prominent role of neuronal signalling pathways asregulators of organismal response to environmental stimuli, PUFAsmay increase the oxidative stress threat for this system, hencejeopardizing its normal function.The continuous degradation and synthesis of RNAs is responsibleof the metabolic changes essential for cell survival, but also of therapid organismal adaptation to new environmental conditions.Oxidative damage to both coding- and non-coding RNAs and theirdegradation control system may therefore affect the regulation ofgene expression and, potentially, result in protein synthesis failure.In turn, this failure may impair the organismal capacity of flexiblyadapting to a novel or unusual input from the internal or externalenvironment [Nunomura et al., 2009; He, 2010]. An importantconsequence of this impairment is the development of neurode-generative disorders. Accumulating evidence suggests that oxida-tiveRNAdamagemayactivelybeinvolvedinthepathomechanismsof neurodegeneration [Nunomura et al., 2009]. Because of itsbiochemical structure, RNAs may be more susceptible to oxidativeinsults than DNA [Nunomura et al., 1999]. RNAs may also be animportant target of oxidation because they are relatively abundantin the cell and they are mostly located in the vicinity ofmitochondria, which are the primary source of ROS [Nunomuraet al., 1999]. As a consequence, oxidative damage to RNA ratherthan DNA may be a more proximate cause of impairment inneuronal functioning through the alteration of brain geneexpression machinery. Specific protective mechanisms of RNAsand their degradation control would be therefore expected to occurin neurons [Houseley and Tollervey, 2009]. May the highsusceptibility of PUFAs to peroxidation indirectly play a role inthe defence system of RNAs and, therefore, of the gene expressionregulatory system inthenervous system? Although thefunctions ofPUFAs in the nervous system are still far from being fullyunderstood, recent studies have shown that PUFAs may affect theexpression of many genes and that these effects appear to beindependent of any changes in membrane composition [de Urquizaet al., 2000; Kitajka et al., 2002, 2004]. It is plausible to speculatethatthehighvulnerabilitytoperoxidationoffreePUFAsinneurons,coupled with their relative abundance in the brain, might play apassive protective role of RNAs, hence limiting their oxidation.Somesupportforthishypothesiscomesfromarecentstudythathassuggested a potential antioxidant role of PUFAs [Kim et al., 2010].Notably, supplementation with omega-3 or omega-6 PUFAs ofcultured neurons from mice lacking the gene encoding palmitoyl-protein thioesterase-1, which mimic infantile neuronal ceroidlipofuscinosis, reduced ROS levels that are normally very high inthese cells [Kim et al., 2010]. Under this scenario, a second questionarises. As PUFAs are major components of neural membranephospholipids and have a critical role in brain signal transductionand neuroplasticity [Davletov and Montecucco, 2010], can PUFAsembedded in the cell membrane contribute to the protection ofRNAs? Weinfer thatthey canlimitthediffusion ofROSinto thecellbecauseoftheirpronenesstobeperoxidized.Thismechanismwouldlimit the intercellular transmission of ROS and that the oxidativecascade will spread to RNAs. Peroxidation of PUFAs in themembrane phospholipids has, however, a number of negativedownstream effects on the cell, such as the decrease in fluidity andincrease in permeability. Consequently, it is of fundamentalimportancetheexistenceofaturnovermechanismthatcompensatesforoxidativePUFAdamage.Manystudieshaveprovidedawealthofevidence that there may be at least two mechanisms regulating the