Energetic response to repeated restraint stress in rapidly growing mice

There is a cost of stress that may result in the loss of normal biological function (e.g., growth). Repeated, and even single, applications of stressors have been shown to induce negative energy balance in rodents. However, here we addressed whether this energetic response changes during multiple stress exposure and whether there is complete recovery subsequent to the cessation of stress exposure. These questions were addressed in growing C57Bl/6 mice (31 day) by determining at different times the energetic and endocrine responses after the exposure to restraint (R) stress for 4 h applied once (R1), repeatedly over 3 days (R3), or repeatedly over 7 days (R7). Compared with control values, R elevated (P<0.05) plasma corticosterone and reduced plasma insulin-like growth factor I on all days of exposure to the stressor. Seven days, but not 1 or 3 days of R, decreased the net growth (126%, P<0.05) and deposition of fat (71%, P<0.05) and lean (60%, P<0.05) energy over the 7 days. Only R7 depressed the 7-day metabolizable energy intake (P<0.05), and R7, but not R1 or R3, increased the overall energy expenditure (10%, P<0.05). Our results demonstrate that repeated episodes of stress are energetically costly to the rapidly growing animal, but compensatory mechanisms mitigate this cost of repeated stress exposure and permit complete recovery of energy balance after the cessation of stress application.     

Effects of corticosterone treatment on growth, development, and the corticosterone response to handling in young Japanese quail (Coturnix coturnix japonica)

Corticosterone, a glucocorticoid secreted during stress responses, has a range of actions that help birds respond to stressors. Although effects of corticosterone treatment have been described in several avian species, the impacts of defined increases in plasma corticosterone on early development and on corticosterone stress responses are little known. These issues were addressed by providing quail with different doses of corticosterone in drinking water from days 8 to 38 post-hatch. The corticosterone dose consumed by each bird during treatment days 15-30 was calculated by measuring water intake. The corticosterone dose was inversely, but weakly, correlated with weights of the bursa, thymus, spleen, liver, testes, oviduct, muscle, and body, and positively correlated with peritoneal fat deposition. When birds were divided into groups based on their corticosterone intake, weights of the spleen, thymus, bursa, muscle, testes, and oviduct were significantly reduced in birds receiving the highest doses; with the exception of muscle, similar reductions were also observed in birds receiving medium doses, and thymic growth was inhibited in birds receiving low doses. The acute corticosterone stress response was measured by handling birds for 15 min. Plasma corticosterone was transiently increased at 15 min in control birds in response to the handling stressor. Some birds consuming low doses of corticosterone had corticosterone responses similar to control birds. Initial corticosterone concentrations were elevated in birds consuming higher doses of corticosterone. Plasma corticosterone in these birds decreased from 0 to 15 min, then increased from 15 to 30 min. The initial decrease could be due to corticosterone clearance, whilst the increase could indicate that the birds had a greater response than control birds to isolation as a stressor. Corticosterone treatment may have reduced the strength of corticosterone negative feedback within the hypothalamo-pituitary-adrenal axis. The results indicate that individuals and organs differ in their sensitivity to corticosterone. Moreover, elevated plasma corticosterone may disrupt the acute corticosterone stress response, and may thus reduce the ability of birds to cope with stressors.     

Exogenous and endogenous corticosterone alter feather quality

We investigated how exogenous and endogenous glucocorticoids affect feather replacement in European starlings (Sturnus vulgaris) after approximately 56% of flight feathers were removed. We hypothesized that corticosterone would retard feather regrowth and decrease feather quality. After feather regrowth began, birds were treated with exogenous corticosterone or sham implants, or endogenous corticosterone by applying psychological or physical (food restriction) stressors. Exogenous corticosterone had no impact on feather length and vane area, but rectrices were lighter than controls. Exogenous corticosterone also decreased inter-barb distance for all feathers and increased barbule number for secondaries and rectrices. Although exogenous corticosterone had no affect on rachis tensile strength and stiffness, barbicel hooking strength was reduced. Finally, exogenous corticosterone did not alter the ability of Bacillus licheniformis to degrade feathers or affect the number of feathers that failed to regrow. In contrast, endogenous corticosterone via food restriction resulted in greater inter-barb distances in primaries and secondaries, and acute and chronic stress resulted in greater inter-barb distances in rectrices. Food-restricted birds had significantly fewer barbules in primaries than chronic stress birds and weaker feathers compared to controls. We conclude that, although exogenous and endogenous corticosterone had slightly different effects, some flight feathers grown in the presence of high circulating corticosterone are lighter, potentially weaker, and with altered feather micro-structure.     

Modulation of corticosterone availability to white adipose tissue of lean and obese Zucker rats by corticosteroid-binding globulin.

Corticosterone-binding (CB) capacity was determined in periovarian and subcutaneous white adipose tissue (WAT), as well as in plasma of lean and obese Zucker rats. In lean rats, plasma CB was twice the level of obese rats. In lean rat WAT, dexamethasone binding accounted for only 0.05-0.09% of corticosterone binding, and aldosterone bound even less; in the obese rats, dexamethasone accounted for 0.2 - 0.3 % of corticosterone binding. Scatchard plots showed that KD for corticosterone was 3.1 nM (WAT) or 3.4 nM (plasma) in lean rats and 1.8 nM (WAT) or 1.5 nM (plasma) in obese rats. The total CB capacity in WAT was lower in the obese than in lean rats (47-50%). Plasma non-esterified fatty acid levels were higher in obese rats. The results suggest that CBG may limit the access of glucocorticoids to adipocytes more weakly in obese rats because of the lower CBG. Fatty acids may increase the affinity of CBG for corticosterone, which would make WAT cells less accessible to circulating glucocorticoids. The modulation of CBG by fatty acids may protect fat reserves by decreasing the sensitivity of WAT to glucocorticoids.     

Focus: The Science of Stress: The Effect of a Combined Fast and Chronic Stress on Body Mass,Blood Metabolites,Corticosterone, and Behavior in House Sparrows (Passer domesticus)

One aspect of the Reactive Scope Model is wear-and-tear, which describes a decrease in an animal’s ability to cope with a stressor, typically because of a period of chronic or repeated stressors. We investigated whether wear-and-tear due to chronic stress would accelerate a transition from phase II to phase III of fasting. We exposed house sparrows (Passer domesticus) to three weeks of daily fasts combined with daily intermittent repeated acute stressors to create chronic stress, followed by two weeks of daily fasts without stressors. We measured circulating glucose, β-hydroxybutyrate (a ketone), and uric acid in both fasted and fed states. We expected birds to be in phase II (high fat breakdown) in a fasted state, but if wear-and-tear accumulated sufficiently, we hypothesized a shift to phase III (high protein breakdown). Throughout the experiment, the birds exhibited elevated β-hydroxybutyrate when fasting but no changes in circulating uric acid, indicating that a transition to phase III did not occur. In both a fasted and fed state, the birds increased glucose mobilization throughout the experiment, suggesting wear-and-tear occurred, but was not sufficient to induce a shift to phase III. Additionally, the birds exhibited a significant decrease in weight, no change in corticosterone, and a transient decrease in neophobia with chronic stress. In conclusion, the birds appear to have experienced wear-and-tear, but our protocol did not accelerate the transition from phase II to phase III of fasting.     

Stress,song and survival in sparrows

The stress response—increases in circulating glucocorticoids following a stressor—is typically considered adaptive, but few studies address the fitness consequences of individual variation in stress response. Generally, due to negative consequences of prolonged elevation of glucocorticoids, animals should have a transient stress response just sufficient to cope with the stressor. In rodents, stress responsiveness is affected by early developmental experience, and hyper-responsiveness to stress is linked to morbidity and mortality. We assessed individual variation in stress responses in free-living song sparrows, Melospiza melodia, in relation to fitness-related measures including song and overwinter survival. Birds with greater increases in corticosterone 30 min following restraint stress were less likely to return to breed the following year. Stress responsiveness was also correlated with song complexity: males with fewer syllables in their song repertoires had greater stress reactivity. Our findings support the hypothesis that developmental stressors both impair song development and affect the adult stress response. Thus, individual variation in the stress response may relate to variation in fitness.     

Stress physiology as a predictor of survival in Galapagos marine iguanas

Although glucocorticoid hormones are considered important physiological regulators for surviving adverse environmental stimuli (stressors), evidence for such a role is sparse and usually extrapolated from glucocorticoid effects under laboratory, short-term and/or non-emergency conditions. Galápagos marine iguanas (Amblyrhynchus cristatus) provide an excellent model for determining the ultimate function of a glucocorticoid response because susceptibility to starvation induced by El Niño conditions is essentially their only major natural stressor. In a prospective study, we captured 98 adult male marine iguanas and assessed four major components of their glucocorticoid response: baseline corticosterone titres; corticosterone responses to acute stressors (capture and handling); the maximal capacity to secrete corticosterone (via adrenocorticotropin injection); and the ability to terminate corticosterone responses (negative feedback). Several months after collecting initial measurements, weak El Niño conditions affected the Galápagos and 23 iguanas died. The dead iguanas were typified by a reduced efficacy of negative feedback (i.e. poorer post-stress suppression of corticosterone release) compared with surviving iguanas. We found no prior differences between dead and alive iguanas in baseline corticosterone concentrations, responses to acute stressors, nor in capacity to respond. These data suggest that a greater ability to terminate a stress response conferred a survival advantage during starvation.     

Effects of dietary CP and amino acid restriction on the growth dynamics of organs and body components in entire male,castrated and female pigs

The optimized use of dietary nutrients and the accurate knowledge of the growth dynamics of body components is important for efficient pig production. This study aimed at evaluating the growth of carcass components and organs of Swiss Large White pigs from birth to 140 kg BW depending on the CP and amino acid (AA) supply. A total of 66 entire males (EM), 58 castrates (CA) and 66 female (FE) pigs were used. From 20 kg BW onwards, they had either ad libitum access to a control (C) or a diet (LP) with 20% lower CP, lysine, methionine + cystine, threonine and tryptophan content compared to C. The weight of organs, primal cuts and external fat were recorded in eight EM and eight FE; at 10 kg BW, on two EM, CA and FE each, and at 20 kg BW, on eight pigs from each sex. From 40 to 140 kg BW at 20 kg intervals, measurements were recorded on four pigs per sex and dietary treatment. The weight of each component was related to empty body (EB) using allometric regressions. Kidneys were heavier (P<0.05) in C- than LP-pigs and in EM than CA and FE. Above 21 kg EB weight, growth rate of LP-FE overpassed (P<0.05) the one of C-pigs. Consequently, LP-FE had heavier (P<0.05) lean cuts than C-pigs in the finisher period. However, LP-CA and LP-EM displayed lower (P<0.05) weights and growth rates of the lean cuts than C-CA and C-EM. Shoulder and loin weights and growth rates were reduced (P<0.05) in LP-pigs when compared to C-pigs. Growth rates of the ham were greater (P<0.05) in LP-FE than C-FE, whereas in LP-EM and LP-CA they were lower (P<0.05) than their C-counterparts. Total amounts of subcutaneous fat, backfat, ham fat and shoulder fat were lower (P<0.05) in C- than LP-pigs. The total amount of subcutaneous fat, backfat and shoulder fat of C-CA was, regardless of diet, greater (P<0.05) than of C-FE. In the LP group, this difference was even more pronounced. The amount of deposited ham fat was greater (P<0.05) in LP-CA than LP-FE, but not in C-CA v. C-FE. Differences in kidney weights suggested a greater nitrogen clearance required in C-pigs. Overall, dietary restriction and sex did not affect all body parts to the same extent. This study further suggests the possibility to reduce the CP and AA supply in FE without compromising the yield of primal lean cuts or increasing the amount of subcutaneous fat.     

Net effects of multiple stressors in freshwater ecosystems: a meta‐analysis

The accelerating rate of global change has focused attention on the cumulative impacts of novel and extreme environmental changes (i.e. stressors), especially in marine ecosystems. As integrators of local catchment and regional processes, freshwater ecosystems are also ranked highly sensitive to the net effects of multiple stressors, yet there has not been a large‐scale quantitative synthesis. We analysed data from 88 papers including 286 responses of freshwater ecosystems to paired stressors and discovered that overall, their cumulative mean effect size was less than the sum of their single effects (i.e. an antagonistic interaction). Net effects of dual stressors on diversity and functional performance response metrics were additive and antagonistic, respectively. Across individual studies, a simple vote‐counting method revealed that the net effects of stressor pairs were frequently more antagonistic (41%) than synergistic (28%), additive (16%) or reversed (15%). Here, we define a reversal as occurring when the net impact of two stressors is in the opposite direction (negative or positive) from that of the sum of their single effects. While warming paired with nutrification resulted in additive net effects, the overall mean net effect of warming combined with a second stressor was antagonistic. Most importantly, the mean net effects across all stressor pairs and response metrics were consistently antagonistic or additive, contrasting the greater prevalence of reported synergies in marine systems. Here, a possible explanation for more antagonistic responses by freshwater biota to stressors is that the inherent greater environmental variability of smaller aquatic ecosystems fosters greater potential for acclimation and co‐adaptation to multiple stressors.     

Impaired Pressure Natriuresis in Obese Youths

Objective: To compare the response and recovery of blood pressure (BP) and sodium excretion (U_NaV) in response to a behavioral stressor in overweight/obese and lean adolescents. Research Methods and Procedures: Twenty‐five lean (12% to 20% body fat) and 59 overweight/obese (>25% body fat) normotensive adolescents were provided all meals for 3 days (average sodium intake, 4000 ± 200 mg/d), before performing the stressor on the third day. There was a 2‐hour pre‐stress rest, followed by a 1‐hour stress (involving a video game task), and a 2‐hour recovery. Percentage of body fat was obtained from DXA. U_NaV was measured hourly, whereas systolic BP and diastolic BP measurements were obtained at 15‐minute intervals, and averaged for each 1‐hour period. Results: There was no significant difference between the lean and overweight/obese group for the response of systolic BP and diastolic BP (group by time interaction, p = 0.60 and p = 0.64, respectively). However, the lean group had a significantly greater increase in U_NaV in response to the stressor compared with the overweight/obese group (p = 0.02). U_NaV remained elevated compared with baseline in both groups at the 1‐hour (p ≤ 0.0001) and 2‐hour (p ≤ 0.0001) post‐time points. Furthermore, there was a tendency for a larger number of sodium retainers in the overweight/obese group compared with the lean group (39.0% vs. 20.0%; χ² = 2.85, df = 1, p = 0.09). Discussion: This study provided evidence that sodium regulation was impaired during a behavioral stress in overweight/obese individuals compared with lean individuals.     

Effects of Acute Restraint Stress,Prolonged Captivity Stress and Transdermal Corticosterone Application on Immunocompetence and Plasma Levels of Corticosterone on the Cururu Toad (Rhinella icterica)

Glucocorticoid steroids modulate immunocompetence in complex ways with both immunoenhancing and immunosuppressive effects in vertebrates exposed to different stressors. Such bimodal effects have been associated with variation in duration and intensity of the stress response. Given that natural populations have been exposed to a multitude of stressors, a better understanding of the functional association between duration and intensity of the stress response, the resulting changes in glucocorticoid plasma levels and their impact on different aspects of immunocompetence emerges as a cornerstone for vertebrate conservation strategies. We investigated the effects of a restraint challenge (with and without movement restriction), long-term captivity, and transdermal corticosterone application on plasma levels of corticosterone (hereinafter referred to as CORT) and different parameters of innate immunocompetence in the male cururu toads (Rhinella icterica). We show that for R. icterica restraint for 24h proved to be a stressful condition, increasing CORT by 3-fold without consistent immunological changes. However, the application of a more intense stressor (restraint with movement restriction), for the same period, potentiated this response resulting in a 9-fold increase in CORT, associated with increase Neutrophil/Lymphocyte ratio (N:L) and a lower bacterial killing ability (BKA). Transdermal application of corticosterone efficiently mimics repeated acute stress response events, without changing the immune parameters even after 13 days of treatment. Interestingly, long-term captivity did not mitigate the stress response, since the toads maintained 3-fold increased CORT even after 3 months under these conditions. Moreover, long-term captivity in the same condition increased total leukocyte count (TLC) and generated an even greater decrease in BKA, suggesting that consequences of the stress response can be aggravated by time in captivity.     

Development of stress response in nestling pied flycatchers

Birds respond to unpredictable events by secreting corticosterone, which induces various responses to cope with stressful situations. However, the evidence is still elusive whether altricial nestlings perceive and respond to external stressors. We investigated the development of adrenocortical stress response to handling-related stressor in nestlings of a small passerine bird, the pied flycatcher (Ficedula hypoleuca). Nestlings were held in isolation from their parents during the experiment to ensure that they indeed respond to handling, not to parental alarm calls. We found that both 9- and 13-day-old nestlings were able to elicit hormonal stress response. Although baseline as well as stress-induced corticosterone levels rose slightly with age, the magnitude of difference between the control and stress-induced levels remained similar in both age groups. However, comparison with adults showed that the stress response of nestlings prior to fledging was still incomplete and significantly lower than in adults. Overall, our results indicate that altricial nestlings do respond to acute stressors, but on the contrary to previous predictions the development of corticosterone stress response during growth period is not gradual and varies remarkably between different passerine species.     

Early Neuroendocrine Alterations in Female Rats Following a Diet Moderately Enriched in Fat

1. High-fat diets disrupt metabolic equilibrium and hypothalamic-pituitary-adrenal axis function and may lead to the development of metabolic and endocrine dysfunctions. The early neuroendocrine responses elicited by a combination of short-term metabolic and emotional stressors is not fully elucidated. 2. The purpose of the present study was to determine the impact on female rats, of a short-term enriched in fat diet, combined with an acute stressor. 3. Adult female Wistar rats were fed a fat diet for 7 days and subsequently exposed to 5 min swimming stress. Plasma leptin, insulin, glucose, luteinizing hormone (LH) and corticosterone, along with brain corticosteroid receptors' mRNAs were measured at 1 h post stress. 4. Diet, compared to chow, reduced food intake and body weight gain, increased leptin and LH, and decreased glucose in the periphery. The diet increased plasma corticosterone and reduced GR mRNA in the hippocampus, similarly to swim stress. 5. The diet significantly modified the animals' response to the subsequent swim stress, by blocking further corticosterone rise and GR mRNA reduction. In addition, exposure of diet-fed rats to stress, altered their endocrine response, in terms of leptin and LH. 6. These observations suggest that even short, moderately unbalanced diets can affect peripheral and central components of energy balance, reproduction and stress response.     

Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor

Glucocorticoid negative feedback regulation of the hypothalamic-pituitary-adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng.10 microl(-1).2 h(-1) icv) or vehicle (300 microl propylene glycol sc or 10 microl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.     

Regulation of protein breakdown and adrenocortical response to stress in birds during migratory flight

During long-term fasting at rest, protein utilization is maintained at low levels until it increases at a threshold adiposity. This study examines 1) whether such a shift in energy substrate use also occurs during endurance exercise while fasting, 2) the role of corticosterone, and 3) the adrenocortical response to an acute stressor. Ten species of migrating birds caught after an endurance flight over at least 500 km were examined. Plasma uric acid and corticosterone levels were low in birds with fat stores >5% of body mass and high in birds with smaller fat stores. Corticosterone levels were very high in birds with no visible fat stores and emaciated breast muscles. Corticosterone levels increased with handling time only in birds with large fat stores. These findings suggest that 1) migrating birds with appreciable fat stores are not stressed by endurance flight, 2) a metabolic shift (increased protein breakdown), regulated by an endocrine shift (medium corticosterone levels), occurs at a threshold adiposity, as observed in birds at rest, 3) adrenocortical response to an acute stressor is inhibited after this shift, and 4) an adrenocortical response typical for an emergency situation (high corticosterone levels) is only reached when muscle protein is dangerously low.     

Differential effects of hemorrhage and LPS on tissue TNF-alpha, IL-1 and associate neuro-hormonal and opioid alterations

LPS administration and hemorrhage are frequently used models for the in vivo study of the stress response. Both challenges stimulate cytokine production as well as activate opiate and neuro-endocrine pathways; which in turn modulate the inflammatory process. Differences in the magnitude and tissue specificity of the proinflammatory cytokine and neuro-hormonal responses to these stressors are not well established. We contrasted the tissue specificity and magnitude of the increase in circulating and tissue cytokine (TNF-alpha, IL-1alpha and IL-1beta) content in response to either fixed-pressure hemorrhage (approximately 40 mm Hg) followed by fluid resuscitation (HEM) or lipopolysaccharide (LPS; 100 microg/100 g BW) administration. LPS and HEM elevated circulating levels of TNF-alpha, while neither stress altered circulating IL-1-alpha and IL-beta. LPS-induced increases in TNF-alpha content were greater than those elicited by HEM in all tissues studied except for the lung, where both stressors produced similar increases. Tissue (lung, spleen and heart) content of IL-1alpha was increased by HEM but was not affected by LPS. Tissue (lung, spleen, and heart) content of IL-1beta was increased by LPS but was not affected by HEM. HEM produced greater increases than LPS in epinephrine (16- vs. 4-fold) and norepinephrine (4-fold vs. 60%) levels and similar elevations in beta-endorphin. LPS produced greater elevation in corticosterone levels (2-fold) than HEM (50%). These results suggest differential tissue cytokine modulation to HEM and LPS, both with respect to target tissue and cytokine type. The hormonal milieu to HEM is characterized by marked catecholaminergic and moderate glucocorticoid while that of LPS is characterized by marked glucocorticoid with moderate catecholaminergic influence.     

Effects of corticosteroids on oxidative damage and circulating carotenoids in captive adult kestrels (Falco tinnunculus)

Birds control body homeostasis through the secretion of corticosterone. This hormone is the end-product of the hypothalamic-pituitary-adrenal (HPA) axis response to stressors. High levels of corticosterone may be associated with low individual fitness and may affect balance between pro-oxidants and antioxidants. Given these points, chronic stress modulated by hormones could undermine individual fitness by increasing oxidative tissue damage. In this study, we administered corticosteroids by diet (20 mg/kg of diet) to captive adult kestrels (Falco tinnunculus) over a 14-day period to evaluate the effects of a simulated chronic stress modulated by corticosteroids. We found that dietary administration of corticosterone caused a 32% increase of reactive oxygen metabolites, but did not impair total serum antioxidant capacity, serum carotenoids or body mass. Oxidative stress had a 64% increase in treated birds compared to 30% in controls. The two groups did not differ in the total serum antioxidant capacity, which showed a significant decrease over the study period. In contrast, circulating carotenoids and body mass increased in both groups. These results suggest that stress hormones, such as corticosterone, may also act as modulators of oxidative stress in birds.     

Does short-term fasting lead to stressed-out parents? A study of incubation commitment and the hormonal stress responses and recoveries in snow petrels

The hormonal stress response is flexible and can be modulated by individuals according to its costs and benefits. Therefore, it is predicted that parents in poor body condition should modify their hormonal stress response, and thus, redirect energy allocation processes from parental care to self-maintenance when stressors occur. To test this prediction, most studies on free-living vertebrates have only focused on the stress response while the stress recovery – how quickly hormonal levels return to baseline values – has been neglected. Moreover, most studies have only focused on corticosterone – the primary mediator of allostasis – without paying attention to prolactin despite its major role in mediating parental behaviors. Here, we examined the effect of a short-term fasting event on the corticosterone and prolactin stress responses and recoveries, and we subsequently explored their relationships with parental decision in the snow petrel (Pagodroma nivea). By comparing the hormonal profiles of fasting and non-fasting snow petrels, we showed that parents modulate their corticosterone (but not prolactin) stress response according to their energetic status. We also described for the first time the hormonal stress recoveries in wild birds and found that they did not differ between fasting and non-fasting birds. Importantly, egg neglect was negatively correlated with circulating prolactin but not corticosterone levels in this species, demonstrating therefore a complex link between body condition, parental behavior and circulating corticosterone and prolactin levels. We suggest that both corticosterone and prolactin play a major role in the way parents adjust to stressors. This multiple signaling may allow parents to fine-tune their response to stressors, and especially, to activate specific allostasis-related mechanisms in a timely manner.     

Habitual physical activity facilitates stress-induced HSP72 induction in brain,peripheral, and immune tissues

The mechanism(s) for how physically active organisms are resistant to many damaging effects of acute stressor exposure is unknown. Cellular induction of heat-shock proteins (e.g., HSP72) is one successful strategy used by the cell to survive the damaging effects of stress. It is possible, therefore, that the stress-buffering effect of physical activity may be due to an improved HSP72 response to stress. Thus the purpose of the current study was to determine whether prior voluntary freewheel running facilitates the stress-induced induction of HSP72 in central (brain), peripheral, and immune tissues. Adult male Fischer 344 rats were housed with either a mobile running wheel (Active) or a locked, immobile wheel [sedentary (Sed)] for 8 wk before stressor exposure. Rats were exposed to either inescapable tail-shock stress (IS; 100 1.6-mA tail shocks, 5-s duration, 60-s intertrial interval), exhaustive exercise stress (EXS; treadmill running to exhaustion), or no stress (controls). Blood, brain, and peripheral tissues were collected 2 h after stressor termination. The kinetics of HSP72 induction after IS was determined in cultured mesenteric lymph node cells. Activation of the stress response was verified by measuring serum corticosterone (RIA). Tissue and cellular HSP72 content were measured using HSP72 ELISA in cell lysates. Both Active and Sed rats had elevated levels of serum corticosterone after stress. In contrast, Active but not Sed rats exposed to IS and/or EXS had elevated HSP72 in dorsal vagal complex, frontal cortex, hippocampus, pituitary, adrenal, liver, spleen, mesenteric lymph nodes, and heart. In addition, Active rats exposed to IS demonstrated a faster induction of lymphocyte HSP72 compared with Sed rats. Thus Active rats responded to stress with both greater and faster HSP72 responses compared with Sed rats. These results indicate that previous physical activity potentiates HSP72 expression after a wide range of stressors. Facilitated induction of HSP72 may contribute to the increased stress resistance previously reported in physically active organisms.     

Illuminating the interrelated immune and endocrine adaptations after multiple exposures to short immobilization stress by in vivo blocking of IL-6

Intermittent psychological stress was induced in adult rats by 2 h/day of immobilization stress for 4 days, with or without blocking the function of IL-6 by using an anti-IL-6 antibody. Basal concentrations of serum corticosterone, IL-1beta, IL-6, and TNF-alpha were assessed 24 h after the last intervention, as were levels of glucocorticoid receptors (GR) and activities of glucocorticoid-inducible enzymes (tyrosine aminotransferase and glutamine synthetase) in muscle and liver. Whole blood cultures were used to assess both spontaneous and LPS-induced reactivity of peripheral blood mononuclear cells. Stress increased corticosterone concentration in a manner partially modulated by IL-6. Serum IL-1beta concentration was downregulated during stress when IL-6 was blocked (P < 0.01). LPS-induced IL-6 secretion by peripheral blood mononuclear cells in vitro correlated positively with serum IL-1beta concentration in antibody-treated groups, independently of stress (R = 0.70 in nonstressed and R = 0.78 in stressed rats; both P < 0.05), whereas serum corticosterone concentration correlated positively with LPS-induced secretion of IL-6 only in control rats (R = 0.66; P < 0.05). Reductions in liver GR levels indicated independent effects of stress (34.5%) and anti-IL-6 antibody (16.7%) and additive effects for both (62.5%). Similar results are reported for vastus muscle. Conversely, stress increased tyrosine aminotransferase and glutamine synthetase activities in muscle and liver with a significant (P < 0.05) effect of anti-IL-6 antibody only seen in stressed livers. In conclusion, IL-6 plays a role in maintaining circulating IL-1beta concentration after multiple exposures to stress, thus promoting a continued elevation of corticosterone release; in peripheral tissues, IL-6 antagonizes the effects of glucocorticoids, especially at the level of GR concentration.