Living Low and Dry: Costs of and Resilience to Soil Hydric Stress in a Fossorial Amphisbaenian Reptile.

In humans, bereavement is associated with an increase in glucocorticoid (GC) levels, though this increase can be mitigated by social support. We examined faecal GC levels and grooming behaviour of free-ranging female baboons to determine whether similar effects were also evident in a non-human species. Females who lost a close relative experienced a significant increase in GC levels in the weeks following their relative's death compared with the weeks before, whereas control females showed no such increase. Despite the fact that females concentrate much of their grooming on close kin, females who lost a close female relative did not experience a decrease in grooming rate and number of grooming partners; instead, both grooming rate and number of grooming partners increased after a relative's death. While the death of a close relative was clearly stressful over the short term, females appeared to compensate for this loss by broadening and strengthening their grooming networks. Perhaps as a result, females' GC levels soon returned to baseline. Even in the presence of familiar troop-mates and other relatives, females experienced a stress response when they lost specific companions, and they apparently sought to alleviate it by broadening and strengthening their social relationships.

Electric fields (EFs) can reduce elevated levels of stress-related hormones in some organisms. In this study, endocrine effects of exposure to a 50 Hz EF were investigated in male BALB/c mice. Specifically, plasma glucocorticoid (GC) levels were examined because GC is known to mediate the stress response in mice, including changes induced by immobilization. Mice were exposed to 50 Hz EFs (at 2.5-200 kV/m) for 60 min. They were immobilized for the latter half (30 min). At the end of exposure period, blood samples were collected and GC levels estimated by spectrofluorometry. GC levels were not influenced by EFs in absence of immobilization, but they were significantly higher in immobilized mice than in non-immobilized mice (P < 0.01). Elevated GC levels induced by immobilization were significantly reduced by exposure to an EF at 10 kV/m (P < 0.05), and the effect of EFs at 0-10 kV/m on GC levels increased in a kV/m-dependent manner (P < 0.05). In contrast, following treatment with EFs at 50 and 200 kV/m, GC levels were higher than those observed at 10 kV/m. To assess the effect of EF treatment duration, mice were also exposed to 50 Hz EFs (10 kV/m) for 6, 20, or 60 min. Immobilization-induced increase in GC levels was significantly suppressed by EF exposure for 20 and 60 min. Therefore, our results demonstrate that extremely low-frequency EFs alter stress response of mice in a kV/m- and duration-dependent manner.

Although extremely low-frequency electric fields (ELF-EF) have been utilised for therapeutic purposes, the biological effect and the underlying mechanism of ELF-EF have not been elucidated. Here, we developed a mouse model of immobilisation-induced increase in glucocorticoid (GC) to evaluate the effect of ELF-EF. Mice were exposed to 50-Hz 10 kV/m EF via a parallel plate electrode and immobilised as needed. The ELF-EF suppressed the immobilisation-induced increase in blood GC level. Here, the results of 32 tests using the model were pooled and analysed. The suppressive effect of ELF-EF on immobilisation-induced increase in GC was reproduced, and the GC level was slightly higher in the ELF-EF-treated mice than in the sham-controlled mice, a novel observation. The immobilisation-induced increase in lactate dehydrogenase, glutamic oxaloacetic transaminase, and glutamic pyruvic transaminase, markers of tissue damage, was suppressed by co-treatment with EF in the biochemical tests using the same plasma sample. In the metabolome analysis, the changes in corticosterones, leukotrienes, and hydroxyeicosatetraenoic acids, markers of inflammation, showed a pattern similar to that of the plasma GC level. Thus, ELF-EF suppresses the stress response that causes an increase in the GC level and slightly promotes GC production in the absence of stress. Moreover, the suppressive effect of ELF-EF on induced stress response might be involved in stress-induced tissue damage or inflammation in immobilised mice. Overall, the model and the data help explore the biological effect of ELF-EF and explain the stress-relieving effect of EF. They would be useful in determining the medical applications of EF in humans and animals.

We determined the effects of voluntary wheel running on the hypothalamic-pituitary-adrenal (HPA) axis, and the peripheral determinants of glucocorticoids action, in male Zucker diabetic fatty (ZDF) rats. Six-week-old euglycemic ZDF rats were divided into Basal, Sedentary, and Exercise groups (n = 8-9 per group). Basal animals were immediately killed, whereas Sedentary and Exercising rats were monitored for 10 wk. Basal (i.e., approximately 0900 AM in the resting state) glucocorticoid levels increased 2.3-fold by week 3 in Sedentary rats where they remained elevated for the duration of the study. After an initial elevation in basal glucocorticoid levels at week 1, Exercise rats maintained low glucocorticoid levels from week 3 through week 10. Hyperglycemia was evident in Sedentary animals by week 7, whereas Exercising animals maintained euglycemia throughout. At the time of death, the Sedentary group had approximately 40% lower glucocorticoid receptor (GR) content in the hippocampus, compared with the Basal and Exercise groups (P < 0.05), suggesting that the former group had impaired negative feedback regulation of the HPA axis. Both Sedentary and Exercise groups had elevated ACTH compared with Basal rats, indicating that central drive of the axis was similar between groups. However, Sedentary, but not Exercise, animals had elevated adrenal ACTH receptor and steroidogenic acute regulatory protein content compared with the Basal animals, suggesting that regular exercise protects against elevations in glucocorticoids by a downregulation of adrenal sensitivity to ACTH. GR and 11beta-hydroxysteroid dehydrogenase type 1 content in skeletal muscle and liver were similar between groups, however, GR content in adipose tissue was elevated in the Sedentary groups compared with the Basal and Exercise (P < 0.05) groups. Thus, the gradual elevations in glucocorticoid levels associated with the development of insulin resistance in male ZDF rats can be prevented with regular exercise, likely because of adaptations that occur primarily in the adrenal glands.

Species-specific patterns in fecal glucocorticoid and androgen levels in zoo-living orangutans (Pongo spp.)

Stress is known to inhibit neuronal growth in the hippocampus. In addition to reducing the size and complexity of the dendritic tree, stress and elevated glucocorticoid levels are known to inhibit adult neurogenesis. Despite the negative effects of stress hormones on progenitor cell proliferation in the hippocampus, some experiences which produce robust increases in glucocorticoid levels actually promote neuronal growth. These experiences, including running, mating, enriched environment living, and intracranial self-stimulation, all share in common a strong hedonic component. Taken together, the findings suggest that rewarding experiences buffer progenitor cells in the dentate gyrus from the negative effects of elevated stress hormones. This chapter considers the evidence that stress and glucocorticoids inhibit neuronal growth along with the paradoxical findings of enhanced neuronal growth under rewarding conditions with a view toward understanding the underlying biological mechanisms.

Parasites are ubiquitous and can strongly affect their hosts through mechanisms such as behavioural changes, increased energetic costs and/or immunomodulation. When parasites are detrimental to their hosts, they should act as physiological stressors and elicit the release of glucocorticoids. Alternatively, previously elevated glucocorticoid levels could facilitate parasite infection due to neuroimmunomodulation. However, results are equivocal, with studies showing either positive, negative or no relationship between parasite infection and glucocorticoid levels. Since factors such as parasite type, infection severity or host age and sex can influence the parasite-glucocorticoid relationship, we review the main mechanisms driving this relationship. We then perform a phylogenetic meta-analysis of 110 records from 65 studies in mammalian hosts from experimental and observational studies to quantify the general direction of this relationship and to identify ecological and methodological drivers of the observed variability. Our review produced equivocal results concerning the direction of the relationship, but there was stronger support for a positive relationship, although causality remained unclear. Mechanisms such as host manipulation for parasite survival, host response to infection, cumulative effects of multiple stressors, and neuro-immunomodulatory effects of glucocorticoids could explain the positive relationship. Our meta-analysis results revealed an overall positive relationship between glucocorticoids and parasitism among both experimental and observational studies. Because all experimental studies included were parasite manipulations, we conclude that parasites caused in general an increase in glucocorticoid levels. To obtain a better understanding of the directionality of this link, experimental manipulation of glucocorticoid levels is now required to assess the causal effects of high glucocorticoid levels on parasite infection. Neither parasite type, the method used to assess parasite infection nor phylogeny influenced the relationship, and there was no evidence for publication bias. Future studies should attempt to be as comprehensive as possible, including moderators potentially influencing the parasite-glucocorticoid relationship. We particularly emphasise the importance of testing hosts of a broad age range, concomitantly measuring sex hormone levels or at least reproductive status, and for observational studies, also considering food availability, host body condition and social stressors to obtain a better understanding of the parasite-glucocorticoid relationship.

BackgroundIUGR infants have qualitative and quantitative abnormalities in lymphocyte function that persist into childhood, resulting in increased susceptibility to infections. We have previously shown in a rat model of IUGR...

There is evidence that an immunoregulatory circuit integrated by immune-derived cytokines and the hypothalamus-pituitary-adrenal (HPA) axis operates during certain pathological conditions. For example, it has been shown that IL-1 is the main mediator of the increase in ACTH and corticosterone blood levels detected in models of viral infection and bacterial endotoxins. This endocrine response has protective effects during septic shock. In experimental models of tumors, there are also clear indications that the increase in glucocorticoid levels detected during the growth of a lymphoma is mediated by immune-derived products and contributes to the inhibition of the inflammatory response. The disruption of the cytokine-HPA axis circuit can predispose to autoimmunity. This has been shown in animal models of spontaneous autoimmune thyroiditis, lupus-like disease, and experimental arthritis. More recently, it has been shown that the proper operation of this circuit contributes to preventing or moderating autoimmunity. The recovery of animals from experimental autoimmune encephalomyelitis (EAE) is clearly dependent on an increase in endogenous glucocorticoid levels. It has been recently shown that this endocrine response is, at least in part, triggered by the immune response to the encephalitogenic antigen and mediated by the endogenous IL-1 produced during the disease. These examples support the concept that the cytokine-HPA circuit plays a protective role during certain pathologies and that its disruption can lead to predisposition to or aggravation of autoimmune diseases.

In mammals, the costs of reproduction are biased towards females. Lactation is particularly energetically expensive, and behavioral and physiological data indicate that maternal effort during lactation induces energetic stress. Another source of stress in females is male aggression directed towards them when they are cycling. Evaluating the costs of reproduction in wild and mobile animals can be a challenging task, and requires detailed information on state-dependent parameters such as hormone levels. Glucocorticoid (GC) levels are indicative of nutritional and social stress, and are widely used to assess the costs of reproduction. We investigated variation in urinary levels of cortisol, the main GC in female bonobos (Pan paniscus), between and within reproductive stages. Female chimpanzees (Pan troglodytes), the closest living relative of the bonobos, are often exposed to intense aggression from males, which causes a significant rise in their cortisol levels during the phase of their maximum fecundity. In bonobos, males compete for access to fertile females, but aggressive male mating strategies are absent in this species. Therefore, we expected that GC levels of cycling female bonobos would be lower than those of lactating females. Due to the long period of offspring care in bonobos, we expected that GC levels would remain elevated into the late stage of lactation, when immatures gain body weight but may still be nursed and carried by their mothers. We found elevated urinary GC levels only during the early stage of lactation. The GC levels of cycling females did not differ from those in the mid or late lactation stage. Behavioral strategies of female bonobos may allow them to compensate for the elevated energetic demands of lactation and prolonged maternal care.

Non-invasive assessment of glucocorticoid and androgen metabolite levels in cooperatively breeding Damaraland mole-rats (Fukomys damarensis)

Animals that are exposed to environmental stressors may experience chronically elevated glucocorticoid (GC) levels, which can lead to deleterious effects such as immune and reproductive system suppression. Such effects are of special concern in rare species. We measured fecal GC concentrations in endangered San Joaquin kit foxes (Vulpes mocrotis mutica) to assess stress responses in natural and urban habitats. Basal GC levels were significantly higher (P < 0.01) among urban foxes (5.3 ± 2.2 ng cortisol/g dry feces; n = 32) than among foxes in natural habitats (4.7 ± 0.5 ng cortisol/g dry feces; n = 179). In the natural habitat, potential stressors included predation risk, particularly in areas with shrubs where coyote (Canis latrans) abundance was higher. In the urban habitat, the primary stressors were anthropogenic disturbances (e.g., human activity, vehicles). Foxes in natural habitats exhibited acute stress responses when trapped, but exhibited similar mean GC levels between areas of high and low predation risk, suggesting adaptation to the presence of coyotes. Urban foxes did not exhibit acute responses when trapped, suggesting adaptation to the presence of humans. Stress responses based on GC levels indicated that foxes in both natural and urban habitats are habituated to the primary stressors in each habitat, thereby mitigating chronic stress.

In mammals, glucocorticoids (GCs) and their intracellular receptor, the glucocorticoid receptor (GR), represent critical checkpoints in the endocrine control of energy homeostasis. Indeed, aberrant GC action is linked to severe metabolic stress conditions as seen in Cushing's syndrome, GC therapy and certain components of the Metabolic Syndrome, including obesity and insulin resistance. Here, we identify the hepatic induction of the mammalian conserved microRNA (miR)-379/410 genomic cluster as a key component of GC/GR-driven metabolic dysfunction. Particularly, miR-379 was up-regulated in mouse models of hyperglucocorticoidemia and obesity as well as human liver in a GC/GR-dependent manner. Hepatocyte-specific silencing of miR-379 substantially reduced circulating very-low-density lipoprotein (VLDL)-associated triglyceride (TG) levels in healthy mice and normalized aberrant lipid profiles in metabolically challenged animals, mediated through miR-379 effects on key receptors in hepatic TG re-uptake. As hepatic miR-379 levels were also correlated with GC and TG levels in human obese patients, the identification of a GC/GR-controlled miRNA cluster not only defines a novel layer of hormone-dependent metabolic control but also paves the way to alternative miRNA-based therapeutic approaches in metabolic dysfunction.

Chronic restraint stress causes anxiety- and depression-like behaviors, downregulates glucocorticoid receptor expression, and attenuates glutamate release induced by brain-derived neurotrophic factor in the prefrontal cortex

Glucocorticoid (GC) hormones are significant regulators of homeostasis. The physiological effects of GCs critically depend on the time of exposure (short vs. long) as well as on their circulating levels (baseline vs. stress-induced). Previous experiments, in which chronic and high elevation of GC levels was induced, indicate that GCs impair both the activity of the immune system and the oxidative balance. Nonetheless, our knowledge on how mildly elevated GC levels, a situation much more common in nature, might influence homeostasis is limited. Therefore, we studied whether an increase in GC level within the baseline range suppresses or enhances condition (body mass, hematocrit and coccidian infestation) and physiological state (humoral innate immune system activity and oxidative balance). We implanted captive house sparrows Passer domesticus with either 60 days release corticosterone (CORT) or control pellets. CORT-treated birds had elevated baseline CORT levels one week after the implantation, but following this CORT returned to its pre-treatment level and the experimental groups had similar CORT levels one and two months following the implantation. The mass of tail feathers grown during the initial phase of treatment was smaller in treated than in control birds. CORT implantation had a transient negative effect on body mass and hematocrit, but both of these traits resumed the pre-treatment values by one month post-treatment. CORT treatment lowered oxidative damage to lipids (malondialdehyde) and enhanced constitutive innate immunity at one week and one month post-implantation. Our findings suggest that a relatively short-term (i.e. few days) elevation of baseline CORT might have a positive and stimulatory effect on animal physiology.