The Arcuate Nucleus: A Site of Fast Negative Feedback for Corticosterone Secretion in Male Rats

PubMed Central

Kawata, Mitsuhiro; Escobar, Carolina

2017-01-01

Abstract Variations in circulating corticosterone (Cort) are driven by the paraventricular nucleus of the hypothalamus (PVN), mainly via the sympathetic autonomic nervous system (ANS) directly stimulating Cort release from the adrenal gland and via corticotropin-releasing hormone targeting the adenohypophysis to release adrenocorticotropic hormone (ACTH). Cort feeds back through glucocorticoid receptors (GRs). Here we show in male Wistar rats that PVN neurons projecting to the adrenal gland do not express GRs, leaving the question of how the ANS in the PVN gets information about circulating Cort levels to control the adrenal. Since the arcuate nucleus (ARC) shows a less restrictive blood–brain barrier, expresses GRs, and projects to the PVN, we investigated whether the ARC can detect and produce fast adjustments of circulating Cort. In low Cort conditions (morning), local microdialysis in the ARC with type I GR antagonist produced a fast and sustained increase of Cort. This was not observed with a type II antagonist. At the circadian peak levels of Cort (afternoon), a type II GR antagonist, but not a type I antagonist, increased Cort levels but not ACTH levels. Antagonist infusions in the PVN did not modify circulating Cort levels, demonstrating the specificity of the ARC to give Cort negative feedback. Furthermore, type I and II GR agonists in the ARC prevented the increase of Cort after stress, demonstrating the role of the ARC as sensor to modulate Cort release. Our findings show that the ARC may be essential to sense blood levels of Cort and adapt Cort secretion depending on such conditions as stress or time of day. PMID:28275717

Acupuncture Stimulation Alleviates Corticosterone-Induced Impairments of Spatial Memory and Cholinergic Neurons in Rats

PubMed Central

Lee, Bombi; Sur, Bong-Jun; Kwon, Sunoh; Jung, Euntaek; Shim, Insop; Lee, Hyejung; Hahm, Dae-Hyun

2012-01-01

The purpose of this study was to examine whether acupuncture improves spatial cognitive impairment induced by repeated corticosterone (CORT) administration in rats. The effect of acupuncture on the acetylcholinergic system was also investigated in the hippocampus. Male rats were subcutaneously injected with CORT (5 mg/kg) once daily for 21 days. Acupuncture stimulation was performed at the HT7 (Sinmun) acupoint for 5 min before CORT injection. HT7 acupoint is located at the end of transverse crease of ulnar wrist of forepaw. In CORT-treated rats, reduced spatial cognitive function was associated with significant increases in plasma CORT level (+36%) and hippocampal CORT level (+204%) compared with saline-treated rats. Acupuncture stimulation improved the escape latency for finding the platform in the Morris water maze. Consistently, the acupuncture significantly alleviated memory-associated decreases in cholinergic immunoreactivity and mRNA expression of BDNF and CREB in the hippocampus. These findings demonstrate that stimulation of HT7 acupoint produced significant neuroprotective activity against the neuronal impairment and memory dysfunction. PMID:22216057

Chronic Glucocorticoids Increase Hippocampal Vulnerability to Neurotoxicity under Conditions That Produce CA3 Dendritic Retraction But Fail to Impair Spatial Recognition Memory

PubMed Central

Conrad, Cheryl D.; McLaughlin, Katie J.; Harman, James S.; Foltz, Cainan; Wieczorek, Lindsay; Lightner, Elizabeth; Wright, Ryan L.

2007-01-01

We previously found that chronic stress conditions producing CA3 dendritic retraction and spatial memory deficits make the hippocampus vulnerable to the neurotoxin ibotenic acid (IBO). The purpose of this study was to determine whether exposure to chronic corticosterone (CORT) under conditions that produce CA3 dendritic retraction would enhance CA3 susceptibility to IBO. Male Sprague Dawley rats were chronically treated for 21 d with CORT in drinking water (400 μg/ml), and half were given daily injections of phenytoin (40 mg/kg), an antiepileptic drug that prevents CA3 dendritic retraction. Three days after treatments stopped, IBO was infused into the CA3 region. Conditions producing CA3 dendritic retraction (CORT and vehicle) exacerbated IBO-induced CA3 damage compared with conditions in which CA3 dendritic retraction was not observed (vehicle and vehicle, vehicle and phenytoin, CORT and phenytoin). Additionally, spatial recognition memory was assessed using the Y-maze, revealing that conditions producing CA3 dendritic retraction failed to impair spatial recognition memory. Furthermore, CORT levels in response to a potentially mild stressor (injection and Y-maze exposure) stayed at basal levels and failed to differ among key groups (vehicle and vehicle, CORT and vehicle, CORT and phenytoin), supporting the interpretations that CORT levels were unlikely to have been elevated during IBO infusion and that the neuroprotective actions of phenytoin were not through CORT alterations. These data are the first to show that conditions with prolonged glucocorticoid elevations leading to structural changes in hippocampal dendritic arbors can make the hippocampus vulnerable to neurotoxic challenges. These findings have significance for many disorders with elevated glucocorticoids that include depression, schizophrenia, Alzheimer’s disease, and Cushing’s disease. PMID:17670974

Acute corticosterone sexually dimorphically facilitates social learning and inhibits feeding in mice.

PubMed

Choleris, Elena; Cazzin, Laura; Lymer, Jennifer M; Amor, Talya R; Lu, Ray; Kavaliers, Martin; Valsecchi, Paola

2013-12-01

In numerous species social learning is predominant and adaptive, yet, we know little of its neurobiological mechanisms. Social learning is modulated by motivations and emotions, in a manner that is often sexually dimorphic. Additionally, stress hormones acutely modulate the related social cognitive process of social recognition. Whether this is true even for social learning is currently unknown. We investigated the acute effects of the stress hormone corticosterone (CORT) on the social transmission of food preferences (STFP) in male and female mice. During a brief social interaction an observer (OBS) acquires a food preference from a same-sex demonstrator (DEM). CORT (1.0, 2.5, 5.0 mg/kg), its ethanol vehicle (0.1%), and saline solution (0.9%) were administered intraperitoneally to the OBS, 10 min before a 30-min social interaction. Levels of plasma CORT were assessed in other mice that had received the same doses of CORT and either had or had not gone through a 30 min social interaction 10 min post-treatment. Exogenous CORT elicited levels of plasma level comparable to those seen at the peak of the circadian cycle and facilitated the STFP with males responding more than females both in terms of the duration of the food preference and the minimum effective dose. CORT also sexually dimorphically inhibited feeding, with females showing a greater dose-response than males. Saline solution and ethanol vehicles also sexually dimorphically facilitated the STFP and reduced feeding, but less than CORT did. These results indicate that CORT facilitates social learning, like social recognition. Hence, CORT may generally increase social information processing. Copyright © 2013 Elsevier Ltd. All rights reserved.

Nutritional stress affects corticosterone deposition in feathers of Caspian tern chicks

USGS Publications Warehouse

Patterson, Allison G. L.; Kitaysky, Alexander S.; Lyons, Donald E.; Roby, Daniel D.

2015-01-01

Stressful environmental conditions affect the adrenocortical function of developing animals, which can have consequences for their fitness. Discovery of the avian stress hormone corticosterone (CORT) in feathers has the potential to broaden the application of endocrine research in ecological and evolutionary studies of wild birds by providing a long-term measure of CORT secretion. Mechanisms of CORT deposition in feathers are not well known and few studies have related feather CORT to circulating plasma CORT during feather growth. Our objective was to experimentally test the validity of using feather CORT as a measure of CORT secretion in developing birds experiencing nutritional stress. Caspian tern Hydroprogne caspia chicks were fed ad libitum or restricted (35% less than ad libitum) diets for four weeks. We measured CORT in feathers from these chicks to examine the relationship between feather CORT concentrations and nutritional limitation, circulating plasma CORT, and feather development. We found that feather CORT was higher in controls fed ad libitum than in restricted individuals, despite higher levels of plasma CORT in restricted chicks compared to controls. Feather mass and growth rates were strongly and positively related to feather CORT concentrations in both treatments. This is the first experimental study to show that feather CORT concentrations can be lower in response to nutritional stress, even when plasma CORT concentrations are elevated. Our results indicate that CORT deposition in feathers may be confounded when feather mass and growth rates are compromised by nutritional stress. We conclude that feather CORT can be used for assessing nutritional stress in growing birds, but the direction of response depends on how strongly stress affects feather development.

Effects of voluntary running on plasma levels of neurotrophins, hippocampal cell proliferation and learning and memory in stressed rats.

PubMed

Yau, S-Y; Lau, B W-M; Zhang, E-D; Lee, J C-D; Li, A; Lee, T M C; Ching, Y-P; Xu, A-M; So, K-F

2012-10-11

Previous studies have shown that a 2-week treatment with 40 mg/kg corticosterone (CORT) in rats suppresses hippocampal neurogenesis and decreases hippocampal brain-derived neurotrophic factor (BDNF) levels and impairs spatial learning, all of which could be counteracted by voluntary wheel running. BDNF and insulin-like growth factor (IGF-1) have been suggested to mediate physical exercise-enhanced hippocampal neurogenesis and cognition. Here we examined whether such running-elicited benefits were accompanied by corresponding changes of peripheral BDNF and IGF-1 levels in a rat model of stress. We examined the effects of acute (5 days) and chronic (4 weeks) treatment with CORT and/or wheel running on (1) hippocampal cell proliferation, (2) spatial learning and memory and (3) plasma levels of BDNF and IGF-1. Acute CORT treatment improved spatial learning without altered cell proliferation compared to vehicle treatment. Acute CORT-treated non-runners showed an increased trend in plasma BDNF levels together with a significant increase in hippocampal BDNF levels. Acute running showed no effect on cognition, cell proliferation and peripheral BDNF and IGF-1 levels. Conversely, chronic CORT treatment in non-runners significantly impaired spatial learning and suppressed cell proliferation in association with a decreased trend in plasma BDNF level and a significant increase in hippocampal BDNF levels. Running counteracted cognitive deficit and restored hippocampal cell proliferation following chronic CORT treatment; but without corresponding changes in plasma BDNF and IGF-1 levels. The results suggest that the beneficial effects of acute stress on cognitive improvement may be mediated by BDNF-enhanced synaptic plasticity that is hippocampal cell proliferation-independent, whereas chronic stress may impair cognition by decreasing hippocampal cell proliferation and BDNF levels. Furthermore, the results indicate a trend in changes of plasma BDNF levels associated with a significant alteration in hippocampal levels, suggesting that treatment with running/CORT for 4 weeks may induce a change in central levels of hippocampal BDNF level, which may not lead to a significant change in peripheral levels. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of Corticosterone and Dietary Energy on Immune Function of Broiler Chickens

PubMed Central

Sheikhahmadi, Ardashir; Wang, Yufeng; Li, Congcong; Jiao, Hongchao; Lin, Hai; Song, Zhigang

2015-01-01

An experiment was conducted to investigate the effects of dietary energy level on the performance and immune function of stressed broiler chickens (Gallus gallus domesticus). A total of 96 three-day-old male broiler chickens (Ross × Ross) were divided into two groups. One group received a high energy (HE) diet and the other group received a low energy (LE) diet for 7 days. At 5 days of age, the chickens from each group were further divided into two sub-groups and received one of the following two treatments for 3 days: (1) subcutaneous injection of corticosterone, twice per day (CORT group; 2 mg of CORT/kg BW in corn oil) and (2) subcutaneous injection of corn oil, twice per day (Control/Sham treatment group). At 10 days of age, samples of blood, duodenum, jejunum, and ileum were obtained. Compared with the other three groups, the LE group treated with CORT had the lowest average daily gain (ADG) and the poorest feed conversion ratio (FCR, P < 0.05). Furthermore, CORT treatment decreased the relative weight (RW) of the bursa independent of the dietary energy level, but it decreased the RW of the thymus only in the chickens fed the LE diet. By contrast, CORT administration decreased the RW of the spleen only in the chickens fed the HE diet (P < 0.05). The plasma total protein, albumin, tumor necrosis factor alpha, interleukin 2 and immunoglobulin G (IgG) levels were affected by the CORT treatment (P < 0.05); however, these factors were not significantly affected by the dietary energy level. Toll-like receptor-5 mRNA level was down-regulated by CORT injection in the duodenum and ileum (P < 0.05) and showed a trend of down-regulation in the jejunum (P=0.0846). The present study showed that CORT treatment induced immunosuppressive effects on the innate immune system of broiler chickens, which were ameliorated by consumption of higher dietary energy. PMID:25803644

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

PubMed

Polich, Rebecca L

2016-01-01

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.

Baseline and stress-induced levels of corticosterone in male and female Afrotropical and European temperate stonechats during breeding.

PubMed

Apfelbeck, Beate; Helm, Barbara; Illera, Juan Carlos; Mortega, Kim G; Smiddy, Patrick; Evans, Neil P

2017-05-22

Latitudinal variation in avian life histories falls along a slow-fast pace of life continuum: tropical species produce small clutches, but have a high survival probability, while in temperate species the opposite pattern is found. This study investigated whether differential investment into reproduction and survival of tropical and temperate species is paralleled by differences in the secretion of the vertebrate hormone corticosterone (CORT). Depending on circulating concentrations, CORT can both act as a metabolic (low to medium levels) and a stress hormone (high levels) and, thereby, influence reproductive decisions. Baseline and stress-induced CORT was measured across sequential stages of the breeding season in males and females of closely related taxa of stonechats (Saxicola spp) from a wide distribution area. We compared stonechats from 13 sites, representing Canary Islands, European temperate and East African tropical areas. Stonechats are highly seasonal breeders at all these sites, but vary between tropical and temperate regions with regard to reproductive investment and presumably also survival. In accordance with life-history theory, during parental stages, post-capture (baseline) CORT was overall lower in tropical than in temperate stonechats. However, during mating stages, tropical males had elevated post-capture (baseline) CORT concentrations, which did not differ from those of temperate males. Female and male mates of a pair showed correlated levels of post-capture CORT when sampled after simulated territorial intrusions. In contrast to the hypothesis that species with low reproduction and high annual survival should be more risk-sensitive, tropical stonechats had lower stress-induced CORT concentrations than temperate stonechats. We also found relatively high post-capture (baseline) and stress-induced CORT concentrations, in slow-paced Canary Islands stonechats. Our data support and refine the view that baseline CORT facilitates energetically demanding activities in males and females and reflects investment into reproduction. Low parental workload was associated with lower post-capture (baseline) CORT as expected for a slow pace of life in tropical species. On a finer resolution, however, this tropical-temperate contrast did not generally hold. Post-capture (baseline) CORT was higher during mating stages in particular in tropical males, possibly to support the energetic needs of mate-guarding. Counter to predictions based on life history theory, our data do not confirm the hypothesis that long-lived tropical populations have higher stress-induced CORT concentrations than short-lived temperate populations. Instead, in the predator-rich tropical environments of African stonechats, a dampened stress response during parental stages may increase survival probabilities of young. Overall our data further support an association between life history and baseline CORT, but challenge the role of stress-induced CORT as a mediator of tropical-temperate variation in life history.

Effect of voluntary wheel running on circadian corticosterone release and on HPA axis responsiveness to restraint stress in Sprague-Dawley rats.

PubMed

Fediuc, Sergiu; Campbell, Jonathan E; Riddell, Michael C

2006-06-01

Adaptations of the hypothalamic-pituitary-adrenal (HPA) axis to voluntary exercise in rodents are not clear, because most investigations use forced-exercise protocols, which are associated with psychological stress. In the present study, we examined the effects of voluntary wheel running on the circadian corticosterone (Cort) rhythm as well as HPA axis responsiveness to, and recovery from, restraint stress. Male Sprague-Dawley rats were divided into exercise (E) and sedentary (S) groups, with E rats having 24-h access to running wheels for 5 wk. Circadian plasma Cort levels were measured at the end of each week, except for week 5 when rats were exposed to 20 min of restraint stress, followed by 95 min of recovery. Measurements of glucocorticoid receptor content in the hippocampus and anterior pituitary were performed using Western blotting at the termination of the restraint protocol. In week 1, circadian Cort levels were twofold higher in E compared with S animals, but the levels progressively decreased in the E group throughout the training protocol to reach similar values observed in S by week 4. During restraint stress and recovery, Cort values were similar between E and S, as was glucocorticoid receptor content in the hippocampus and pituitary gland after death. Compared with E, S animals had higher plasma ACTH levels during restraint. Taken together, these data indicate that 5 wk of wheel running are associated with normal circadian Cort activity and normal negative-feedback inhibition of the HPA axis, as well as with increased adrenal sensitivity to ACTH after restraint stress.

Exogenous corticosterone and nest abandonment: a study in a long-lived bird, the Adélie penguin.

PubMed

Spée, Marion; Marchal, Lorène; Lazin, David; Le Maho, Yvon; Chastel, Olivier; Beaulieu, Michaël; Raclot, Thierry

2011-09-01

Breeding individuals enter an emergency life-history stage when their body reserves reach a minimum threshold. Consequently, they redirect current activity toward survival, leading to egg abandonment in birds. Corticosterone (CORT) is known to promote this stage. How and to what extent CORT triggers egg abandonment when breeding is associated with prolonged fasting, however, requires further investigation. We manipulated free-living male Adélie penguins with CORT-pellets before their laying period. We then examined their behavioral response with respect to nest abandonment in parallel with their prolactin levels (regulating parental care), and the subsequent effects of treatment on breeding success in relieved birds. Exogenous CORT triggered nest abandonment in 60% of the treated penguins ~14 days after treatment and induced a concomitant decline in prolactin levels. Interestingly, prolactin levels in treated penguins that did not abandon their nest were higher at the point of implantation and also after being relieved by females, when compared with abandoning penguins. Among successful birds, the treatment did not affect the number of chicks, nor the brood mass. Our results show the involvement of CORT in the decision-making process regarding egg abandonment in Adélie penguins when incubation is associated with a natural long fast. However, we suggest that CORT alone is not sufficient to trigger nest abandonment but that 1) prolactin levels need to reach a low threshold value, and 2) a rise in proteolysis (i.e. utilization of protein as main energy substrate) seems also to be required. Copyright © 2011 Elsevier Inc. All rights reserved.

Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice.

PubMed

Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R; Lawrence, Catherine B; Coll, Anthony P; White, Anne

2016-11-01

Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances.

Elevated Hypothalamic Glucocorticoid Levels Are Associated With Obesity and Hyperphagia in Male Mice

PubMed Central

Sefton, Charlotte; Harno, Erika; Davies, Alison; Small, Helen; Allen, Tiffany-Jayne; Wray, Jonathan R.; Lawrence, Catherine B.; Coll, Anthony P.

2016-01-01

Glucocorticoid (Gc) excess, from endogenous overproduction in disorders of the hypothalamic-pituitary-adrenal axis or exogenous medical therapy, is recognized to cause adverse metabolic side effects. The Gc receptor (GR) is widely expressed throughout the body, including brain regions such as the hypothalamus. However, the extent to which chronic Gcs affect Gc concentrations in the hypothalamus and impact on GR and target genes is unknown. To investigate this, we used a murine model of corticosterone (Cort)-induced obesity and analyzed Cort levels in the hypothalamus and expression of genes relevant to Gc action. Mice were administered Cort (75 μg/mL) or ethanol (1%, vehicle) in drinking water for 4 weeks. Cort-treated mice had increased body weight, food intake, and adiposity. As expected, Cort increased plasma Cort levels at both zeitgeber time 1 and zeitgeber time 13, ablating the diurnal rhythm. Liquid chromatography dual tandem mass spectrometry revealed a 4-fold increase in hypothalamic Cort, which correlated with circulating levels and concentrations of Cort in other brain regions. This occurred despite decreased 11β-hydroxysteroid dehydrogenase (Hsd11b1) expression, the gene encoding the enzyme that regenerates active Gcs, whereas efflux transporter Abcb1 mRNA was unaltered. In addition, although Cort decreased hypothalamic GR (Nr3c1) expression 2-fold, the Gc-induced leucine zipper (Tsc22d3) mRNA increased, which indicated elevated GR activation. In keeping with the development of hyperphagia and obesity, Cort increased Agrp, but there were no changes in Pomc, Npy, or Cart mRNA in the hypothalamus. In summary, chronic Cort treatment causes chronic increases in hypothalamic Cort levels and a persistent elevation in Agrp, a mediator in the development of metabolic disturbances. PMID:27649090

Exogenous prenatal corticosterone exposure mimics the effects of prenatal stress on adult brain stress response systems and fear extinction behavior.

PubMed

Bingham, Brian C; Sheela Rani, C S; Frazer, Alan; Strong, Randy; Morilak, David A

2013-11-01

Exposure to early-life stress is a risk factor for the development of cognitive and emotional disorders later in life. We previously demonstrated that prenatal stress (PNS) in rats results in long-term, stable changes in central stress-response systems and impairs the ability to extinguish conditioned fear responding, a component of post-traumatic stress disorder (PTSD). Maternal corticosterone (CORT), released during prenatal stress, is a possible mediator of these effects. The purpose of the present study was to investigate whether fetal exposure to CORT at levels induced by PNS is sufficient to alter the development of adult stress neurobiology and fear extinction behavior. Pregnant dams were subject to either PNS (60 min immobilization/day from ED 14-21) or a daily injection of CORT (10mg/kg), which approximated both fetal and maternal plasma CORT levels elicited during PNS. Control dams were given injections of oil vehicle. Male offspring were allowed to grow to adulthood undisturbed, at which point they were sacrificed and the medial prefrontal cortex (mPFC), hippocampus, hypothalamus, and a section of the rostral pons containing the locus coeruleus (LC) were dissected. PNS and prenatal CORT treatment decreased glucocorticoid receptor protein levels in the mPFC, hippocampus, and hypothalamus when compared to control offspring. Both treatments also decreased tyrosine hydroxylase levels in the LC. Finally, the effect of prenatal CORT exposure on fear extinction behavior was examined following chronic stress. Prenatal CORT impaired both acquisition and recall of cue-conditioned fear extinction. This effect was additive to the impairment induced by previous chronic stress. Thus, these data suggest that fetal exposure to high levels of maternal CORT is responsible for many of the lasting neurobiological consequences of PNS as they relate to the processes underlying extinction of learned fear. The data further suggest that adverse prenatal environments constitute a risk factor for PTSD-like symptomatology, especially when combined with chronic stressors later in life. Copyright © 2013 Elsevier Ltd. All rights reserved.

The nexus of hair corticosterone level, immunocompetence, metabolic rates and overwinter survival in the root vole, Microtus oeconomus.

PubMed

Książek, Aneta; Zub, Karol; Szafrańska, Paulina A; Wieczorek, Monika; Konarzewski, Marek

2017-09-01

Although corticosterone (CORT) regulates many physiological mechanisms, the associations between CORT levels, immunocompetence, energy expenditures and overwinter survival have not been examined. Here, we studied individual variation in CORT level extracted from hair, immunocompetence quantified as the neutrophil-to-lymphocyte (N/L) ratio, total white blood cells (WBC) and natural antibody levels (NAbs), along with the resting (RMR) and peak metabolic rates (PMR) and mortality during three consecutive winter seasons in a natural population of the root vole, Microtus oeconomus. In early winter, hair CORT level was strongly positively associated with body mass and inversely related to voles' ability to survive. We suggest that the observed association between hair CORT level and body mass may be the key component of the physiological nexus driving the survivorship of individual rodents. Additionally, hair CORT was a significant predictor of variation of the whole body RMR, which in turn enhanced overwinter survival in the studied population. On the other hand, hair CORT was not significantly associated with changes in the blood indices. Interestingly, the analysis carried out only during the first year of study (2008), which was characterized by a high population density and prevalence of infestation with a blood protozoan, Babesia spp., showed that the intensity of the infestation was negatively correlated with both the hair CORT level and the N/L ratio. Because CORT is often considered immunosuppressive, we expected a positive association between its level and the N/L ratio. However, hair CORT did not significantly correlate with the N/L ratio. We suggest that the lack of an association between hair CORT and the N/L ratio resulted from a small inter-individual variation in the N/L ratio in 2008, which was much higher and less variable than in the other years of our study. Copyright © 2017 Elsevier Inc. All rights reserved.

Exogenous glucocorticoids and a high-fat diet cause severe hyperglycemia and hyperinsulinemia and limit islet glucose responsiveness in young male Sprague-Dawley rats.

PubMed

Beaudry, Jacqueline L; D'souza, Anna M; Teich, Trevor; Tsushima, Robert; Riddell, Michael C

2013-09-01

Corticosterone (CORT) and other glucocorticoids cause peripheral insulin resistance and compensatory increases in β-cell mass. A prolonged high-fat diet (HFD) induces insulin resistance and impairs β-cell insulin secretion. This study examined islet adaptive capacity in rats treated with CORT and a HFD. Male Sprague-Dawley rats (age ∼6 weeks) were given exogenous CORT (400 mg/rat) or wax (placebo) implants and placed on a HFD (60% calories from fat) or standard diet (SD) for 2 weeks (N = 10 per group). CORT-HFD rats developed fasting hyperglycemia (>11 mM) and hyperinsulinemia (∼5-fold higher than controls) and were 15-fold more insulin resistant than placebo-SD rats by the end of ∼2 weeks (Homeostatic Model Assessment for Insulin Resistance [HOMA-IR] levels, 15.08 ± 1.64 vs 1.0 ± 0.12, P < .05). Pancreatic β-cell function, as measured by HOMA-β, was lower in the CORT-HFD group as compared to the CORT-SD group (1.64 ± 0.22 vs 3.72 ± 0.64, P < .001) as well as acute insulin response (0.25 ± 0.22 vs 1.68 ± 0.41, P < .05). Moreover, β- and α-cell mass were 2.6- and 1.6-fold higher, respectively, in CORT-HFD animals compared to controls (both P < .05). CORT treatment increased p-protein kinase C-α content in SD but not HFD-fed rats, suggesting that a HFD may lower insulin secretory capacity via impaired glucose sensing. Isolated islets from CORT-HFD animals secreted more insulin in both low and high glucose conditions; however, total insulin content was relatively depleted after glucose challenge. Thus, CORT and HFD, synergistically not independently, act to promote severe insulin resistance, which overwhelms islet adaptive capacity, thereby resulting in overt hyperglycemia.

Ethological endophenotypes are altered by elevated stress hormone levels in both Huntington's disease and wildtype mice.

PubMed

Mo, Christina; Renoir, Thibault; Hannan, Anthony J

2014-11-01

Huntington's disease (HD) is an autosomal dominant, neurodegenerative disorder with cognitive, psychiatric, motor, neuroendocrine and peripheral dysfunctions. Symptom onset and progression can be closely modeled in HD transgenic mice, which facilitate the search for therapeutics and environmental modulators. In the first investigation of chronic stress in HD, we have previously shown that administering a moderate dose of the stress hormone, corticosterone (CORT) had no effect on short-term memory in wildtype (WT) mice but accelerated the onset of the impairment in male R6/1 HD mice. We now extend this investigation to ethological dysfunctions in HD, which we hypothesized to be more susceptible to CORT treatment compared to the same functions in WT littermates. Both genotypes consumed similar doses of CORT dissolved in drinking water across 6-14 weeks of age and were assessed for olfactory sensitivity, nest-building, saccharin preference as well as vocal responses to sociosexual stimuli. In female HD and WT mice, olfactory sensitivity and saccharin preference were reduced by 2 and 4 weeks of CORT, respectively. In males, there was no effect of CORT on saccharin preference, however the number of vocalizations to a female mouse was transiently increased by CORT-drinking, regardless of genotype. Nest-building was severely impaired in HD mice at an early age, but was unaffected by CORT. Our results suggest that the presence of the HD mutation had no bearing on CORT-induced effects at this dose, suggesting that even moderately elevated stress hormone levels can impair ethological behaviors in both the HD and healthy brain. Copyright © 2014 Elsevier B.V. All rights reserved.

No evidence for an effect of traffic noise on the development of the corticosterone stress response in an urban exploiter.

PubMed

Angelier, Frédéric; Meillère, Alizée; Grace, Jacquelyn K; Trouvé, Colette; Brischoux, François

2016-06-01

Anthropogenic noise can have important physiological and behavioral effects on wild animals. For example, urban noise could lead to a state of chronic stress and could alter the development of the hypothalamus-pituitary-adrenal (HPA) axis. Supporting this hypothesis, several studies have found that human disturbance is associated with increased circulating corticosterone (CORT) levels. However, it remains unclear whether increased CORT levels are the result of anthropogenic noise or other anthropogenic factors. Here, we experimentally tested the impact of urban noise on the CORT stress response in an urban exploiter (the house sparrow, Passer domesticus) by exposing chicks to a traffic noise ('disturbed chicks') or not ('control chicks'). If noise exposure has a negative impact on developing chicks, we predicted that (1) disturbed chicks will grow slower, will be in poorer condition, and will have a lower fledging probability than controls; (2) disturbed chicks will have higher baseline CORT levels than control; (3) the CORT stress response will be affected by this noise exposure. Contrary to these predictions, we found no effect of our experiment on growth, body condition, and fledging success, suggesting that house sparrow chicks were not negatively affected by this noise exposure. Moreover, we did not find any effect of noise exposure on either baseline CORT levels or the CORT stress response of chicks. This suggests not only that house sparrow chicks did not perceive this noise as stressful, but also that the development of the HPA axis was not affected by such noise exposure. Our study suggests that, contrary to urban avoiders, urban exploiters might be relatively insensitive to urban noise during their development. Further comparative studies are now needed to understand whether such insensitivity to anthropogenic noise is a consistent phenomenon in urban exploiters and whether this is a major requirement of an urban way of life. Copyright © 2015 Elsevier Inc. All rights reserved.

High post-partum levels of corticosterone given to dams influence postnatal hippocampal cell proliferation and behavior of offspring: A model of post-partum stress and possible depression.

PubMed

Brummelte, Susanne; Pawluski, Jodi L; Galea, Liisa A M

2006-09-01

Post-partum stress and depression (PPD) have a significant effect on child development and behavior. Depression is associated with hypercortisolism in humans, and the fluctuating levels of hormones, including corticosterone, during pregnancy and the post-partum, may contribute to PPD. The present study was developed to investigate the effects of high-level corticosterone (CORT) post-partum in the mother on postnatal neurogenesis and behavior in the offspring. Sprague-Dawley dams were treated with either CORT (40 mg/kg) or sesame oil injections daily for 26 days beginning the day after giving birth. Dams were tested in the forced swim test (FST) and in the open field test (OFT) on days 24-26 post-partum. Results showed that the dams exposed to CORT expressed "depressive-like" behavior compared to controls, with decreased struggling behavior and increased immobility in the FST. To investigate the effects of treatment on hippocampal postnatal cell proliferation and survival in the offspring, males and females from treated dams were injected with BrdU (50 mg/kg) on postnatal day 21 and perfused either 24 h (cell proliferation) or 21 days (cell survival) later. Furthermore, male and female offspring from each litter were tested in adulthood on various behavioral tests, including the forced swim test, open field test, resistance to capture test and elevated plus maze. Intriguingly, male, but not female, offspring of CORT-treated dams exhibited decreased postnatal cell proliferation in the dentate gyrus. Both male and female offspring of CORT-treated dams showed higher resistance to capture and greater locomotor activity as assessed in the open field test. As high levels of CORT may be a characteristic of stress and/or depression, these findings support a model of 'CORT-induced' post-partum stress and possibly depression and demonstrate that the offspring of affected dams can exhibit changes in postnatal neurogenesis and behavior in adulthood.

Response of testosterone and corticosterone plasma levels to the challenge of sibling competition: a study in common terns.

PubMed

Braasch, Alexander; Becker, Peter H; Groothuis, Ton G G

2014-08-01

The hormonal response to social challenges has been widely studied, however, most work focused on adult behavior in a reproductive context although developing animals also encounter important social challenges early in life. We studied the relationship between acute sibling competition and plasma corticosterone (CORT) and testosterone (T) in common tern (Sterna hirundo) chicks, a species whose young compete for access to food by scramble interactions. Blood samples were taken in nests with two and only one single chick both immediately after a feeding bout and in non-challenged controls. We found that T levels were lower in siblings challenged by a feeding bout as compared to controls, which may be explained by the fact that T suppresses begging behavior and is only elevated in response to territorial intrusion but not sibling competition in a related species. Singletons had, corrected for body condition, generally lower CORT levels than siblings suggesting that growing up with siblings creates a competitive environment in which high CORT levels are sustained irrespective of a social challenge. CORT levels were also negatively correlated with body condition and were higher in males than in females. The latter may be related to sex-specific food requirements and susceptibility to stress. Our results suggest a possible suppressive effect of acute sibling competition on T secretion, and a positive effect on CORT levels by longer term sibling competition. The degree to which these dynamics are related to begging or aggression, or both, needs further experimental work. Copyright © 2014 Elsevier Inc. All rights reserved.

Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats.

PubMed

Mao, Qing-Qiu; Huang, Zhen; Ip, Siu-Po; Xian, Yan-Fang; Che, Chun-Tao

2012-02-01

Repeated injections of corticosterone (CORT) induce the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depressive-like behavior. This study aimed to examine the antidepressant-like effect and the possible mechanisms of total glycosides of peony (TGP) in the CORT-induced depression model in rats. The results showed that the 3-week CORT injections induced the significant increase in serum CORT levels in rats. Repeated CORT injections also caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Moreover, it was found that brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus and frontal cortex were significantly decreased in CORT-treated rats. Treatment of the rats with TGP significantly suppressed the depression-like behavior and increased brain BDNF levels in CORT-treated rats. The results suggest that TGP produces an antidepressant-like effect in CORT-treated rats, which is possibly mediated by increasing BDNF expression in the hippocampus and frontal cortex. Copyright © 2011 Elsevier B.V. All rights reserved.

Effects of population density on corticosterone levels of prairie voles in the field

PubMed Central

Blondel, Dimitri V.; Wallace, Gerard N.; Calderone, Stefanie; Gorinshteyn, Marija; St. Mary, Colette M.; Phelps, Steven M.

2015-01-01

High population density is often associated with increased levels of stress-related hormones, such as corticosterone (CORT). Prairie voles (Microtus ochrogaster) are a socially monogamous species known for their large population density fluctuations in the wild. Although CORT influences the social behavior of prairie voles in the lab, the effect of population density on CORT has not previously been quantified in this species in the field. We validated a non-invasive hormone assay for measuring CORT metabolites in prairie vole feces. We then used semi-natural enclosures to experimentally manipulate population density, and measured density effects on male space use and fecal CORT levels. Our enclosures generated patterns of space use and social interaction that were consistent with previous prairie vole field studies. Contrary to the positive relationship between CORT and density typical of other taxa, we found that lower population densities (80 animals/ha) produced higher fecal CORT than high densities (240/ha). Combined with prior work in the lab and field, the data suggest that high prairie vole population densities indicate favorable environments, perhaps through reduced predation risk. Lastly, we found that field animals had lower fecal CORT levels than laboratory-living animals. The data emphasize the usefulness of prairie voles as models for integrating ecological, evolutionary and mechanistic questions in social behavior. PMID:26342968

Rehabilitation modality and onset differentially influence whisker sensory hypersensitivity after diffuse traumatic brain injury in the rat.

PubMed

Thomas, Theresa Currier; Stockhausen, Ellen Magee; Law, L Matthew; Khodadad, Aida; Lifshitz, Jonathan

2017-01-01

As rehabilitation strategies advance as therapeutic interventions, the modality and onset of rehabilitation after traumatic brain injury (TBI) are critical to optimize treatment. Our laboratory has detected and characterized a late-onset, long-lasting sensory hypersensitivity to whisker stimulation in diffuse brain-injured rats; a deficit that is comparable to visual or auditory sensory hypersensitivity in humans with an acquired brain injury. We hypothesize that the modality and onset of rehabilitation therapies will differentially influence sensory hypersensitivity in response to the Whisker Nuisance Task (WNT) as well as WNT-induced corticosterone (CORT) stress response in diffuse brain-injured rats and shams. After midline fluid percussion brain injury (FPI) or sham surgery, rats were assigned to one of four rehabilitative interventions: (1) whisker sensory deprivation during week one or (2) week two or (3) whisker stimulation during week one or (4) week two. At 28 days following FPI and sham procedures, sensory hypersensitivity was assessed using the WNT. Plasma CORT was evaluated immediately following the WNT (aggravated levels) and prior to the pre-determined endpoint 24 hours later (non-aggravated levels). Deprivation therapy during week two elicited significantly greater sensory hypersensitivity to the WNT compared to week one (p < 0.05), and aggravated CORT levels in FPI rats were significantly lower than sham levels. Stimulation therapy during week one resulted in low levels of sensory hypersensitivity to the WNT, similar to deprivation therapy and naïve controls, however, non-aggravated CORT levels in FPI rats were significantly higher than sham. These data indicate that modality and onset of sensory rehabilitation can differentially influence FPI and sham rats, having a lasting impact on behavioral and stress responses to the WNT, emphasizing the necessity for continued evaluation of modality and onset of rehabilitation after TBI.

Maternal corticosterone exposure in the mouse programs sex-specific renal adaptations in the renin-angiotensin-aldosterone system in 6-month offspring.

PubMed

Cuffe, James S M; Burgess, Danielle J; O'Sullivan, Lee; Singh, Reetu R; Moritz, Karen M

2016-04-01

Short-term maternal corticosterone (Cort) administration at mid-gestation in the mouse reduces nephron number in both sexes while programming renal and cardiovascular dysfunction in 12-month male but not female offspring. The renal renin-angiotensin-aldosterone system (RAAS), functions in a sexually dimorphic manner to regulate both renal and cardiovascular physiology. This study aimed to identify if there are sex-specific differences in basal levels of the intrarenal RAAS and to determine the impact of maternal Cort exposure on the RAAS in male and female offspring at 6 months of age. While intrarenal renin concentrations were higher in untreated females compared to untreated males, renal angiotensin II concentrations were higher in males than females. Furthermore, basal plasma aldosterone concentrations were greater in females than males. Cort exposed male but not female offspring had reduced water intake and urine excretion. Cort exposure increased renal renin concentrations and elevated mRNA expression of Ren1, Ace2, and Mas1 in male but not female offspring. In addition, male Cort exposed offspring had increased expression of the aldosterone receptor, Nr3c2 and renal sodium transporters. In contrast, Cort exposure increased Agtr1a mRNA levels in female offspring only. This study demonstrates that maternal Cort exposure alters key regulators of renal function in a sex-specific manner at 6 months of life. These finding likely contribute to the disease outcomes in male but not female offspring in later life and highlights the importance of renal factors other than nephron number in the programming of renal and cardiovascular disease. © 2016 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.

Ecological correlates of cortisol levels in two bat species with contrasting feeding habits.

PubMed

Lewanzik, Daniel; Kelm, Detlev H; Greiner, Sabine; Dehnhard, Martin; Voigt, Christian C

2012-05-15

The immediate release of adrenal glucocorticoids can be crucial for an animal's survival when facing a stressor, but constantly elevated or exceptionally high glucocorticoid levels are usually detrimental for health. Although baseline and maximal secretion of glucocorticoids are regulated within narrow ranges within species, plasma glucocorticoid levels vary largely across vertebrates. We asked what ecological factors affect baseline plasma cortisol levels (CortI) and maximum levels (CortMax) following a physiological challenge through administration of adrenocorticotropic hormone (ACTH). Specifically, we studied whether seasonal fluctuations in food abundance correlate with the capacity of cortisol increases in two phyllostomid bat species with contrasting feeding habits: the sanguinivorous vampire bat (Desmodus rotundus) and the frugivorous short-tailed fruit bat (Carollia perspicillata). Both species coexist in habitats with various levels of seasonality (dry and rainforest). On a seasonal basis, resource abundance is more stable for vampire than for fruit bats, but previous studies suggested that daily foraging success may vary more for vampire than for fruit bats. CortI and CortMax varied seasonally in C. perspicillata from dry and rainforests, with the exception of CortMax in rainforest bats. Although we expected food availability to be stable year-round for vampire bats, we found CortI and CortMax of vampires to be higher during the rainy season than during the dry season. Also, we found CortMax to be higher in vampires from the rainforest than in those from the dry forest. CortMax of vampires were among the highest measured for a free-ranging mammal; a pattern that could be related to the species' vulnerability to starvation. We conclude that food availability modulates cortisol levels in free-ranging species that face seasonally fluctuating resources; in species, however, that benefit from food which is constantly abundant, other factors than food may become more important in modulating cortisol levels. Copyright © 2012 Elsevier Inc. All rights reserved.

Experimental increase in baseline corticosterone level reduces oxidative damage and enhances innate immune response

PubMed Central

Pătraș, Laura; Pap, Péter L.; Vincze, Orsolya; Mureșan, Cosmin; Németh, József; Lendvai, Ádám Z.

2018-01-01

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. PMID:29432437

Seasonal changes in adrenocortical responses to acute stress in Eurasian tree sparrow (Passer montanus) on the Tibetan Plateau: comparison with house sparrow (P. domesticus) in North America and with the migratory P. domesticus in Qinghai Province.

PubMed

Li, Dongming; Wang, Gang; Wingfield, John C; Zhang, Zhi; Ding, Changqing; Lei, Fumin

2008-08-01

Seasonal modulation of the adrenocortical response to stress appears to be ubiquitous in arctic-breeding and temperate-zone-breeding birds, but has not been well investigated in alpine-breeding species at mid-latitude. We examined the adrenocortical response to acute stress (capture, handling and restraint) in populations of Eurasian tree sparrow (Passer montanus) among seasons and migratory house sparrow (P. domesticus bactrianus) in pre-breeding on the Qinghai-Xizang Plateau (the Tibetan Plateau). A population of house sparrow (Passer domesticus domesticus) was also sampled in lowland Phoenix, Arizona during breeding and wintering stages. In Eurasian tree sparrows, baseline corticosterone (CORT) does not differ among life history stages, but stress-induced CORT level (maximal CORT, total and corrected integrated CORT) is significantly higher in late breeding stage than those in early breeding and prebasic molt stages. In house sparrows, stress-induced CORT level does not differ between sites and life history stages, but baseline CORT is significantly lower in pre-breeding from Qinghai compared with those in breeding and wintering stages from Phoenix. Interestingly, both baseline CORT and maximal CORT do not differ between the populations of Eurasian tree sparrow and house sparrow in early/pre-breeding stage although tree sparrow is resident species whereas house sparrow is migratory in Qinghai. Our results suggest that the extreme environment of the Tibetan Plateau does not have significant effects on adrenocortical responses to acute stress in Eurasian tree sparrows and house sparrows, which may be a result of masking by human activities. These invasive human commensals may have a unique HPA axis response to different environments because they can take advantage of human food sources and shelter (i.e. buildings).

Corticosterone profiles in northern cardinals (Cardinalis cardinalis): Do levels vary through life history stages?

PubMed

Duckworth, Benjamin M; Jawor, Jodie M

2018-07-01

As animals move through life history stages, energy requirements for each stage will vary. Both daily and annual variation in the glucocoriticoid hormones (specifically corticosterone, or CORT, in birds) helps provide the variable energy needed through life history stages. In many bird species, CORT is higher in the breeding season when energy demands can be quite high and is often lower in the non-breeding season. Additionally, CORT has a role to play in the response to stressful stimuli and the level to which CORT is elevated following stressful events can vary through the annual cycle as well. Here we report on baseline and stress-induced CORT levels in both sexes of northern cardinals, Cardinalis cardinalis, a non-migrating, year-round territorial species across life history stages. Corticosterone is overall higher in the non-breeding season than the breeding season in both sexes. Males tend to have higher levels of stress-induced CORT than females, although the observed patterns are complex. Our findings differ from one of the more common profile reported in songbirds where breeding season CORT tends to be higher than non-breeding levels. A strong influence may be the prolonged breeding season seen in cardinals; lower levels of CORT during breeding may guard against adverse maternal effects, interruptions in breeding behaviors, or egg production. Additional investigation of species with similar ecologies to northern cardinals, and more populations of cardinals, may show that annual glucocorticoid profiles are more labile than previously appreciated. Copyright © 2018 Elsevier Inc. All rights reserved.

Effects of population density on corticosterone levels of prairie voles in the field.

PubMed

Blondel, Dimitri V; Wallace, Gerard N; Calderone, Stefanie; Gorinshteyn, Marija; St Mary, Colette M; Phelps, Steven M

2016-01-01

High population density is often associated with increased levels of stress-related hormones, such as corticosterone (CORT). Prairie voles (Microtus ochrogaster) are a socially monogamous species known for their large population density fluctuations in the wild. Although CORT influences the social behavior of prairie voles in the lab, the effect of population density on CORT has not previously been quantified in this species in the field. We validated a non-invasive hormone assay for measuring CORT metabolites in prairie vole feces. We then used semi-natural enclosures to experimentally manipulate population density, and measured density effects on male space use and fecal CORT levels. Our enclosures generated patterns of space use and social interaction that were consistent with previous prairie vole field studies. Contrary to the positive relationship between CORT and density typical of other taxa, we found that lower population densities (80 animals/ha) produced higher fecal CORT than higher densities (240/ha). Combined with prior work in the lab and field, the data suggest that high prairie vole population densities indicate favorable environments, perhaps through reduced predation risk. Lastly, we found that field animals had lower fecal CORT levels than laboratory-living animals. The data emphasize the usefulness of prairie voles as models for integrating ecological, evolutionary, and mechanistic questions in social behavior. Copyright © 2015 Elsevier Inc. All rights reserved.

Corticosterone mediated costs of reproduction link current to future breeding.

PubMed

Crossin, Glenn T; Phillips, Richard A; Lattin, Christine R; Romero, L Michael; Williams, Tony D

2013-11-01

Life-history theory predicts that costs are associated with reproduction. One possible mediator of costs involves the secretion of glucocorticoid hormones, which in birds can be measured in feathers grown during the breeding period. Glucocorticoids mediate physiological responses to unpredictable environmental or other stressors, but they can also function as metabolic regulators during more predictable events such as reproduction. Here we show that corticosterone ("Cort") in feathers grown during the breeding season reflects reproductive effort in two Antarctic seabird species (giant petrels, Macronectes spp.). In females of both species, but not males, feather Cort ("fCort") was nearly 1.5-fold higher in successful than failed breeders (those that lost their eggs/chicks), suggesting a cost of successful reproduction, i.e., high fCort levels in females reflect the elevated plasma Cort levels required to support high metabolic demands of chick-rearing. Successful breeding also led to delayed moult prior to winter migration. The fCort levels and pre-migration moult score that we measured at the end of current breeding were predictive of subsequent reproductive effort in the following year. Birds with high fCort and a delayed initiation of moult were much more likely to defer breeding in the following year. Cort levels and the timing of moult thus provide a potential mechanism for the tradeoff between current and future reproduction. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Baseline glucocorticoids are drivers of body mass gain in a diving seabird

USGS Publications Warehouse

Hennin, Holly; Berlin, Alicia; Love, Oliver P.

2016-01-01

Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic–pituitary–adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

Baseline glucocorticoids are drivers of body mass gain in a diving seabird.

PubMed

Hennin, Holly L; Wells-Berlin, Alicia M; Love, Oliver P

2016-03-01

Life-history trade-offs are influenced by variation in individual state, with individuals in better condition often completing life-history stages with greater success. Although resource accrual significantly impacts key life-history decisions such as the timing of reproduction, little is known about the underlying mechanisms driving resource accumulation. Baseline corticosterone (CORT, the primary avian glucocorticoid) mediates daily and seasonal energetics, responds to changes in food availability, and has been linked to foraging behavior, making it a strong potential driver of individual variation in resource accrual and deposition. Working with a captive colony of white-winged scoters (Melanitta fusca deglandi), we aimed to causally determine whether variation in baseline CORT drives individual body mass gains mediated through fattening rate (plasma triglycerides corrected for body mass). We implanted individuals with each of three treatment pellets to elevate CORT within a baseline range in a randomized order: control, low dose of CORT, high dose of CORT, then blood sampled and recorded body mass over a two-week period to track changes in baseline CORT, body mass, and fattening rates. The high CORT treatment significantly elevated levels of plasma hormone for a short period of time within the biologically relevant, baseline range for this species, but importantly did not inhibit the function of the HPA (hypothalamic-pituitary-adrenal) axis. Furthermore, an elevation in baseline CORT resulted in a consistent increase in body mass throughout the trial period compared to controls. This is some of the first empirical evidence demonstrating that elevations of baseline CORT within a biologically relevant range have a causal, direct, and positive influence on changes in body mass.

The components of somatostatin and ghrelin systems are altered in neuroendocrine lung carcinoids and associated to clinical-histological features.

PubMed

Herrera-Martínez, Aura D; Gahete, Manuel D; Sánchez-Sánchez, Rafael; Salas, Rosa Ortega; Serrano-Blanch, Raquel; Salvatierra, Ángel; Hofland, Leo J; Luque, Raúl M; Gálvez-Moreno, María A; Castaño, Justo P

2017-07-01

Lung carcinoids (LCs) are rare tumors that comprise 1-5% of lung malignancies but represent 20-30% of neuroendocrine tumors. Their incidence is progressively increasing and a better characterization of these tumors is required. Alterations in somatostatin (SST)/cortistatin (CORT) and ghrelin systems have been associated to development/progression of various endocrine-related cancers, wherein they may become useful diagnostic, prognostic and therapeutic biomarkers. We aimed to evaluate the expression levels of ghrelin and SST/CORT system components in LCs, as well as to explore their putative relationship with histological/clinical characteristics. An observational retrospective study was performed; 75 LC patients with clinical/histological characteristics were included. Samples from 46 patients were processed to isolate mRNA from tumor and adjacent non-tumor region, and the expression levels of SST/CORT and ghrelin systems components, determined by quantitative-PCR, were compared to those of 7 normal lung tissues. Patient cohort was characterized by mean age 53±15 years, 48% males, 34% with tobacco exposure; 71.4/28.6% typical/atypical carcinoids, 21.7% incidental tumors, 4.3% functioning tumors, 17.7% with metastasis. SST/CORT and ghrelin system components were expressed at variable levels in a high proportion of tumors, as well as in adjacent non-tumor tissues, while a lower proportion of normal lung samples also expressed these molecules. A gradation was observed from normal non-neoplastic lung tissues, non-tumor adjacent tissue and LCs, being SST, sst4, sst5, GHS-R1a and GHS-R1b overexpressed in tumor tissue compared to normal tissue. Importantly, several SST/CORT and ghrelin system components displayed significant correlations with relevant clinical parameters, such as necrosis, peritumoral and vascular invasion, or metastasis. Altogether, these data reveal a prominent, widespread expression of key SST/CORT/ghrelin system components in LCs, where they display clinical-histological correlations, which could provide novel, valuable markers for NET patient management. Copyright © 2017 Elsevier B.V. All rights reserved.

Feed contamination with Fusarium mycotoxins induces a corticosterone stress response in broiler chickens.

PubMed

Antonissen, G; De Baere, S; Devreese, M; Van Immerseel, F; Martel, A; Croubels, S

2017-01-01

The aim of the present study was to evaluate the effect of the Fusarium mycotoxins deoxynivalenol (DON) and fumonisins (FBs) on the stress response in broiler chickens, using corticosterone (CORT) in plasma as a biomarker. Chickens were fed either a control diet, a DON contaminated diet, a FBs contaminated diet, or a DON and FBs contaminated diet for 15 d at concentrations close to the European Union maximum guidance levels for DON and FBs in poultry. Mean plasma CORT levels were significantly higher in broiler chickens fed a DON contaminated and a DON and FBs contaminated diet compared to birds fed a control diet. A similar trend was observed for animals fed a FBs contaminated diet. Consequently, feeding broilers a diet contaminated with DON and/or FBs induced a CORT stress response, which may indicate a negative effect on animal welfare. © 2016 Poultry Science Association Inc.

Does corticosterone mediate predator-induced responses of larval Hylarana indica?

PubMed

Joshi, A M; Wadekar, N V; Gramapurohit, N P

2017-09-15

Prey-predator interactions have been studied extensively in terms of morphological and behavioural responses of prey to predation risk using diverse model systems. However, the underlying physiological changes associated with morphological, behavioural or life historical responses have been rarely investigated. Herein, we studied the effect of chronic predation risk on larval growth and metamorphosis of Hylarana indica and the underlying physiological changes in prey tadpoles. In the first experiment, tadpoles were exposed to a caged predator from Gosner stage 25-42 to record growth and metamorphosis. Further, whole body corticosterone (CORT) was measured to determine the physiological changes underlying morphological and life historical responses of these prey tadpoles. Surprisingly, tadpoles experiencing continuous predation risk grew and developed faster and metamorphosed at a larger size. Interestingly, these tadpoles had significantly lower CORT levels. In the second experiment, tadpoles were exposed to predation risk (PR) or PR+CORT from stage 25-42 to determine the role of CORT in mediating predator-induced responses of H. indica. Tadpoles facing continuous predation risk grew and developed faster and metamorphosed at a larger size reinforcing the results of the first experiment. However, when CORT was administered along with predation risk, tadpoles grew and developed slowly leading to delayed metamorphosis. Interestingly, growth and metamorphic traits of tadpoles exposed to PR+CORT were comparable to those of the control group indicating that exogenous CORT nullified the positive effect of predation risk. Apparently, CORT mediates predator-induced morphological responses of H. indica tadpoles by regulating their physiology. Copyright © 2016 Elsevier Inc. All rights reserved.

The relation between fearfulness in young and stress-response in adult laying hens, on individual and group level.

PubMed

de Haas, Elske N; Kops, Marjolein S; Bolhuis, J Elizabeth; Groothuis, Ton G G; Ellen, Esther D; Rodenburg, T Bas

2012-10-10

Fearfulness of an individual can affect its sensitivity to stress, while at the same time the social situation in which an animal lives can affect its fear level. It is however unknown what the long-term effects of high fearfulness on sensitivity to stress are, on individual or group level in laying hens. We hypothesize that increased fearfulness at a young age results in increased sensitivity to stress at an adult age, and that this relation can differ between groups, due to differences in group composition. Therefore, we studied the relation between fearfulness in an Open Field (OF) test at six weeks of age and plasma-corticosterone (CORT) levels after a 5-min Manual Restraint test (MR) at 33 weeks of age, and assessed behavior in the home pen. We used birds from a low mortality line, selected for four generations on low mortality due to feather pecking and cannibalism and a control line (n=153 in total, eight pens/line). These lines are known to differ in fearfulness and stress physiology. Chicks from the low mortality line were more active in the OF compared to chicks from the control line. Chicks that showed a fearful response (no walking, no vocalizing) in the OF test had higher CORT at 33 weeks of age than chicks that walked and/or vocalized in the OF test and had higher activity in the home pen as adults. On group level, a passive response in the OF was related to high CORT levels after MR. Presence of at least one fearful bird in a group led to higher CORT in the other group mates compared to birds from groups with no fearful birds present. Birds from groups in which more than 50% of birds had severe comb lesions had higher CORT levels compared to birds from groups with less than 50% of birds affected. High fearfulness of laying hen chicks can on individual level have a long-term effect on stress sensitivity. The presence of fearful birds in a group as well as signs of social instability in a group, indicated by comb lesions, can affect sensitivity to stress of birds from the same group. The mechanism by which this occurs can lie in social transmission of (fear related) behavior, but this suggestion needs further investigation. Copyright © 2012 Elsevier Inc. All rights reserved.

The adrenocortical response of tufted puffin chicks to nutritional deficits

USGS Publications Warehouse

Kitaysky, A.S.; Romano, Marc D.; Piatt, John F.; Wingfield, J.C.; Kikuchi, M.

2005-01-01

In several seabirds, nutritional state of a nest-bound chick is negatively correlated with the activity of its hypothalamus-pituitary-adrenal (HPA) axis. Increased corticosterone (cort) secretion has been shown to facilitate changes in behavior that allow hungry chicks to obtain more food from parents. However, if parents are not willing/able to buffer their young from temporary food shortages, increased cort secretion could be detrimental to undernourished chicks. In a system where parents are insensitive to chick demands, low benefits and high costs of activation of the HPA-axis in hungry chicks should lead to a disassociation of the nutritional state of the young and the activity of its HPA-axis. We tested this novel hypothesis for the tufted puffin (Fratercula cirrhata), a seabird with intermittent provisioning of a nest-bound semi-precocial chick. We examined the HPA-axis activity of captive chicks exposed to the following: (1) a short-term (24 h) food deprivation; and (2) an array of prolonged (3 weeks) restrictions in feeding regimens. We found that in response to a short-term food deprivation chicks decreased baseline levels of cort and thyroid hormones. In response to prolonged restrictions, food-limited chicks exhibited signs of nutritional deficit: they had lower body mass, endogenous lipid reserves, and thyroid hormone titers compared to chicks fed ad libitum. However, baseline and maximum acute stress-induced levels of cort were also lower in food-restricted chicks compared to those of chicks fed ad libitum. These results support a major prediction of the study hypothesis that puffin chicks suppress HPA-axis activity in response to short- and long-term nutritional deficits. This physiological adaptation may allow a chick to extend its development in the nest, while eluding detrimental effects of chronic cort elevation. 

Relative contributions of pituitary-adrenal hormones to the ontogeny of behavioral inhibition in the rat.

PubMed

Takahashi, L K; Kim, H

1995-04-01

Recent investigations revealed that adrenalectomized (ADX) rat pups exhibit deficits in behavioral inhibition. Furthermore, administration of exogenous corticosterone (CORT) restores behavioral inhibition in ADX pups. Although these studies suggest that CORT has an important role in the development of behavioral inhibition, the relative behavioral effects of elevated pituitary hormone secretion induced by ADX are not known. Therefore, experiments were conducted to assess the potential behavioral effects of elevated adrenocorticotropin (ACTH) secretion induced by ADX and to further evaluate the contribution of endogenous CORT to the development of behavioral inhibition. In Experiment 1., we verified that 10-day-old ADX rats exhibit high levels of plasma ACTH throughout the preweaning period associated with the development of behavioral inhibition. In Experiment 2, 10-day-old pups were hypophysectomized (HYPOX) and ADX and were compared behaviorally to sham-operated controls on day 14. When tested in the presence of an anesthetized unfamiliar adult male rat, HYPOX + ADX pups exhibited low levels of freezing accompanied by ultrasonic vocalizations. These pups also had reduced concentrations of plasma ACTH and CORT. In Experiment 3, 10-day-old pups were HYPOX and tested for behavioral inhibition on day 14. In comparison to sham-operated controls, HYPOX rats exhibited significantly lower levels of freezing and had reduced plasma concentrations of ACTH and CORT. Results demonstrate clearly that deficits in freezing occur even in the presence of low plasma ACTH concentrations. Therefore, elevated secretion of pituitary hormones is not a major factor that contributes to the ADX-induced deficits in behavioral inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Corticosterone stress response and plasma metabolite levels during breeding and molt in a free-living migratory songbird, the wood thrush (Hylocichla mustelina).

PubMed

Done, Tyler; Gow, Elizabeth A; Stutchbury, Bridget J M

2011-04-01

Many birds face energetic trade-offs between different life history stages, such as reproductive effort, feather molt and the non-breeding period. Little is known about how physiological measures of condition (corticosterone, plasma metabolites) in free-living birds change from nesting stages to the post-breeding molt period or whether this is influenced by prior reproductive effort. We evaluated whether corticosterone (CORT) and plasma metabolite levels vary with date, nest stage and sex in a free-living migratory songbird, the wood thrush (Hylocichla mustelina). We also tested whether (1) baseline CORT levels early in the season were predictive of subsequent reproductive success and (2) whether prior reproductive effort influenced CORT levels and blood metabolites during molt. Baseline CORT levels decreased with date during both the incubation stage and nestling stage, but did not vary significantly across stage of breeding season. Stress-induced CORT declined with date during incubation and varied significantly across breeding stage, with lower levels during feather molt. Profiles of the metabolites of β-hydroxybutyrate, glycerol, and triglyceride did not vary significantly with date or breeding stage. Only triglycerides varied significantly with sex, with females having higher levels than males. Reproductive output was highly variable (0-10 fledglings per season) but baseline CORT levels in females during the first incubation period of the season was not related to subsequent reproductive output. Prior reproductive effort, measured as the cumulative number of young hatched during the breeding season, was positively related to stress-induced CORT during molt. High reproductive effort in wood thrush appears to have physiological carry-over effects into the molt period which could potentially affect rate of molt and preparation for fall migration. Copyright © 2011. Published by Elsevier Inc.

Effects of corticosterone on contextual fear consolidation in intact and ovariectomized female rats.

PubMed

Kashefi, Adel; Rashidy-Pour, Ali

2014-10-01

Previous studies have shown that post-training administration of glucocorticoids enhances memory consolidation in male rats, but theirs effects on female rats are not known. Thus, this study was conducted to examine the effects of corticosterone (CORT) on contextual fear memory consolidation in intact and ovariectomized (OVX) female rats. In Experiment 1, post-training administration of CORT (0.3, 3, and 10 mg/kg) to OVX female rats impaired memory consolidation at a 0.3 mg dose of CORT. In Experiment 2, post-training injection of CORT (0.3 mg/kg) to female rats in proestrus stage (when the levels of estrogens are highest) enhances and in the estrus stage (when the levels of estrogens are lowest) impaired memory retention. In Experiment 3, OVX female rats injected with CORT (0.3 mg/kg) and one of the three doses of 17β-estradiol (1, 10 or 100 μg/kg) following training. 48-h memory retention test indicated that CORT enhanced memory retention in OVX female rats that received concurrent injection of 10 or 100 μg doses of 17β-estradiol. These findings indicate that cognitive effects of CORT in female rats can be modulated with the plasma levels of estrogens: when the levels of estrogens are low, corticosterone has a negative effect, while when the levels of estrogens are high; the corticosterone has a positive enhancing effect. Copyright © 2014 Elsevier Inc. All rights reserved.

The impact of reproduction on the stress axis of free-living male northern red backed voles (Myodes rutilus).

PubMed

Fletcher, Quinn E; Dantzer, Ben; Boonstra, Rudy

2015-12-01

Activation of the hypothalamic-pituitary-adrenal (HPA) axis culminates in the release of glucocorticoids (henceforth CORT), which have wide-reaching physiological effects. Three hypotheses potentially explain seasonal variation in CORT. The enabling hypothesis predicts that reproductive season CORT exceeds post-reproductive season CORT because CORT enables reproductive investment. The inhibitory hypothesis predicts the opposite because CORT can negatively affect reproductive function. The costs of reproduction hypothesis predicts that HPA axis condition declines over and following the reproductive season. We tested these hypotheses in wild male red-backed voles (Myodes rutilus) during the reproductive and post-reproductive seasons. We quantified CORT levels in response to restraint stress tests consisting of three blood samples (initial, stress-induced, and recovery). Mineralocorticoid (MR) and glucocorticoid (GR) receptor mRNA levels in the brain were also quantified over the reproductive season. Total CORT (tCORT) in the initial and stress-induced samples were greater in the post-reproductive than in the reproductive season, which supported the inhibitory hypothesis. Conversely, free CORT (fCORT) did not differ between the reproductive and post-reproductive seasons, which was counter to both the enabling and inhibitory hypotheses. Evidence for HPA axis condition decline in CORT as well as GR and MR mRNA over the reproductive season (i.e. costs of reproduction hypothesis) was mixed. Moreover, all of the parameters that showed signs of declining condition over the reproductive season did not also show signs of declining condition over the post-reproductive season suggesting that the costs resulting from reproductive investment had subsided. In conclusion, our results suggest that different aspects of the HPA axis respond differently to seasonal changes and reproductive investment. Copyright © 2015 Elsevier Inc. All rights reserved.

Activation of mineralocorticoid receptors by exogenous glucocorticoids and the development of cardiovascular inflammatory responses in adrenalectomized rats.

PubMed

Young, Morag J; Morgan, James; Brolin, Kim; Fuller, Peter J; Funder, John W

2010-06-01

Activation of the mineralocorticoid receptor (MR) in the context of a high salt intake produces cardiovascular inflammation plus cardiac fibrosis and failure. Inactivation of vascular 11beta-hydroxysteroid dehydrogenase type 2 activity in intact animals by carbenoxolone (CBX) produces a similar pathology, presumably reflecting coronary vascular MR activation by endogenous glucocorticoids. To test this hypothesis, we have used adrenalectomized rats, without endogenous corticosteroids, and examined the consequences of corticosterone (CORT) replacement on a series of cardiovascular disease parameters. Uninephrectomized adrenalectomized Sprague Dawley rats given 1% NaCl/0.3% KCl to drink were treated for 8 d as follows: control; 20 mg deoxycorticosterone (DOC); 2 mg/d CORT; 2.5 mg/d CBX; CORT plus CBX (CORT/CBX); and CORT/CBX plus 100 mg/kg.d eplerenone. Markers of cardiac oxidative stress (p22(phox) and NOX4 mRNA) were up-regulated in the DOC and CORT/CBX groups; in contrast, inflammatory cell infiltration was increased and endothelial nitric oxide synthase down-regulated by CORT as well as by DOC and CORT/CBX. In the kidney, connective tissue growth factor mRNA levels were increased by DOC and CORT/CBX; in contrast, DOC had no effect on mRNA levels for channel inducing factor or endothelin 3, which were elevated only by CORT/CBX. All changes noted were reversed by eplerenone. Rats given 10-fold lower CORT (0.2 mg/d) with or without CBX showed no change in any parameter. These results suggest that there exist distinct but overlapping ligand-specific MR-mediated tissue responses to a classic mineralocorticoid (DOC) and to the glucocorticoid CORT, in the presence and absence of CBX to block vascular 11beta-hydroxysteroid dehydrogenase type 2.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat.

PubMed

Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan; Thomas, Theresa C

2016-07-01

As many as 20-55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration-deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic-pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. © 2016 The authors.

Diffuse traumatic brain injury affects chronic corticosterone function in the rat

PubMed Central

Rowe, Rachel K; Rumney, Benjamin M; May, Hazel G; Permana, Paska; Adelson, P David; Harman, S Mitchell; Lifshitz, Jonathan

2016-01-01

As many as 20–55% of patients with a history of traumatic brain injury (TBI) experience chronic endocrine dysfunction, leading to impaired quality of life, impaired rehabilitation efforts and lowered life expectancy. Endocrine dysfunction after TBI is thought to result from acceleration–deceleration forces to the brain within the skull, creating enduring hypothalamic and pituitary neuropathology, and subsequent hypothalamic–pituitary endocrine (HPE) dysfunction. These experiments were designed to test the hypothesis that a single diffuse TBI results in chronic dysfunction of corticosterone (CORT), a glucocorticoid released in response to stress and testosterone. We used a rodent model of diffuse TBI induced by midline fluid percussion injury (mFPI). At 2months postinjury compared with uninjured control animals, circulating levels of CORT were evaluated at rest, under restraint stress and in response to dexamethasone, a synthetic glucocorticoid commonly used to test HPE axis regulation. Testosterone was evaluated at rest. Further, we assessed changes in injury-induced neuron morphology (Golgi stain), neuropathology (silver stain) and activated astrocytes (GFAP) in the paraventricular nucleus (PVN) of the hypothalamus. Resting plasma CORT levels were decreased at 2months postinjury and there was a blunted CORT increase in response to restraint induced stress. No changes in testosterone were measured. These changes in CORT were observed concomitantly with altered complexity of neuron processes in the PVN over time, devoid of neuropathology or astrocytosis. Results provide evidence that a single moderate diffuse TBI leads to changes in CORT function, which can contribute to the persistence of symptoms related to endocrine dysfunction. Future experiments aim to evaluate additional HP-related hormones and endocrine circuit pathology following diffuse TBI. PMID:27317610

Feather corticosterone reveals developmental stress in seabirds.

PubMed

Will, Alexis P; Suzuki, Yuya; Elliott, Kyle H; Hatch, Scott A; Watanuki, Yutaka; Kitaysky, Alexander S

2014-07-01

In nest-bound avian offspring, food shortages typically trigger a release of the stress hormone corticosterone (CORT). Recent studies indicate that CORT is passively deposited in the tissue of growing feathers and thus may provide an integrated measure of stress incurred during development in the nest. The current hypothesis predicts that, assuming a constant rate of feather growth, elevated CORT circulating in the blood corresponds to higher levels of CORT in feather tissue, but experimental evidence for nutritionally stressed chicks is lacking. Here, we examined how food limitation affects feather CORT content in the rhinoceros auklet (Cerorhinca moncerata). We (i) used captive chicks reared on control versus restricted diets, and (ii) applied this technique to free-living chicks with unknown nutritional histories that fledged at three separate colonies. We found that (i) feather growth was not affected by experimentally induced nutritional stress; (ii) captive chicks raised on a restricted diet had higher levels of CORT in their primary feathers; (iii) feather CORT deposition is a sensitive method of detecting nutritional stress; and (iv) free-living fledglings from the colony with poor reproductive performance had higher CORT in their primary feathers. We conclude that feather CORT is a sensitive integrated measure revealing the temporal dynamics of food limitations experienced by rhinoceros auklet nestlings. The use of feather CORT may be a powerful endocrine tool in ecological and evolutionary studies of bird species with similar preferential allocation of limited resources to feather development. © 2014. Published by The Company of Biologists Ltd.

Chronic corticosterone affects brain weight, and mitochondrial, but not glial volume fraction in hippocampal area CA3.

PubMed

Coburn-Litvak, P S; Tata, D A; Gorby, H E; McCloskey, D P; Richardson, G; Anderson, B J

2004-01-01

Corticosterone (CORT), the predominant glucocorticoid in rodents, is known to damage hippocampal area CA3. Here we investigate how that damage is represented at the cellular and ultrastructural level of analyses. Rats were injected with CORT (26.8 mg/kg, s.c.) or vehicle for 56 days. Cell counts were estimated with the physical disector method. Glial and mitochondrial volume fractions were obtained from electron micrographs. The effectiveness of the CORT dose used was demonstrated in two ways. First, CORT significantly inhibited body weight gain relative to vehicles. Second, CORT significantly reduced adrenal gland, heart and gastrocnemius muscle weight. Both the adrenal and gastrocnemius muscle weight to body weight ratios were also significantly reduced. Although absolute brain weight was reduced, the brain to body weight ratio was higher in the CORT group relative to vehicles, suggesting that the brain is more resistant to the effects of CORT than many peripheral organs and muscles. Consistent with that interpretation, CORT did not alter CA3 cell density, cell layer volume, or apical dendritic neuropil volume. Likewise, CORT did not significantly alter glial volume fraction, but did reduce mitochondrial volume fraction. These findings highlight the need for ultrastructural analyses in addition to cellular level analyses before conclusions can be drawn about the damaging effects of prolonged CORT elevations. The relative reduction in mitochondria may indicate a reduction in bioenergetic capacity that, in turn, could render CA3 vulnerable to metabolic challenges.

Fear-related behaviors in Lurcher mutant mice exposed to a predator.

PubMed

Lorivel, T; Roy, V; Hilber, P

2014-11-01

The Lurcher mutant mice are characterized by massive cerebellar cortex degeneration. Besides their motor and cognitive disturbances, they exhibit both exaggerated blood corticosterone (CORT) level surge and behavioral disinhibition when confronted to anxiogenic conditions (i.e. to a potential threat). In this study, we assessed if such physiological and behavioral hyperactivity was also detectable in a fear-eliciting situation (actual threat). For this purpose, the behaviors and CORT level elevations in Lurcher mice were compared with those of littermate controls in the predator exposure test: mice were exposed either to a rat (exposure) or to a brief wave of the experimenter's hand (sham exposure). While the basal CORT concentrations (24 h before testing) were not significantly different between mice of both genotypes, the post-exposure ones were higher in Lurcher than in control mice whatever the condition of the experimental design (exposure or sham exposure). Predator exposure did not provoke significant increase of CORT levels whatever the genotype. On the contrary, our data clearly showed that fear-related behaviors of cerebellar mutants facing a real threat were exacerbated in comparison to those of control mice. These results suggest that the cerebellar cortex not only participates to fear conditioning and anxiety but also actively contributes to the modulation of the innate fear-related behaviors. © 2014 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Long-term continuous corticosterone treatment decreases VEGF receptor-2 expression in frontal cortex.

PubMed

Howell, Kristy R; Kutiyanawalla, Ammar; Pillai, Anilkumar

2011-01-01

Stress and increased glucocorticoid levels are associated with many neuropsychiatric disorders including schizophrenia and depression. Recently, the role of vascular endothelial factor receptor-2 (VEGFR2/Flk1) signaling has been implicated in stress-mediated neuroplasticity. However, the mechanism of regulation of VEGF/Flk1 signaling under long-term continuous glucocorticoid exposure has not been elucidated. We examined the possible effects of long-term continuous glucocorticoid exposure on VEGF/Flk1 signaling in cultured cortical neurons in vitro, mouse frontal cortex in vivo, and in post mortem human prefrontal cortex of both control and schizophrenia subjects. We found that long-term continuous exposure to corticosterone (CORT, a natural glucocorticoid) reduced Flk1 protein levels both in vitro and in vivo. CORT treatment resulted in alterations in signaling molecules downstream to Flk1 such as PTEN, Akt and mTOR. We demonstrated that CORT-induced changes in Flk1 levels are mediated through glucocorticoid receptor (GR) and calcium. A significant reduction in Flk1-GR interaction was observed following CORT exposure. Interestingly, VEGF levels were increased in cortex, but decreased in serum following CORT treatment. Moreover, significant reductions in Flk1 and GR protein levels were found in postmortem prefrontal cortex samples from schizophrenia subjects. The alterations in VEGF/Flk1 signaling following long-term continuous CORT exposure represents a molecular mechanism of the neurobiological effects of chronic stress.

Maternal and fetal metabonomic alterations in prenatal nicotine exposure-induced rat intrauterine growth retardation.

PubMed

Feng, Jiang-hua; Yan, You-e; Liang, Gai; Liu, Yan-song; Li, Xiao-jun; Zhang, Ben-jian; Chen, Liao-bin; Yu, Hong; He, Xiao-hua; Wang, Hui

2014-08-25

Prenatal nicotine exposure causes adverse birth outcome. However, the corresponding metabonomic alterations and underlying mechanisms of nicotine-induced developmental toxicity remain unclear. The aims of this study were to characterize the metabolic alterations in biofluids in nicotine-induced intrauterine growth retardation (IUGR) rat model. In the present study, pregnant Wistar rats were intragastrically administered with different doses of nicotine (0.5, 1.0 and 2.0 mg/kg d) from gestational day (GD) 11-20. The metabolic profiles of the biofluids, including maternal plasma, fetal plasma and amniotic fluid, were analyzed using (1)H nuclear magnetic resonance (NMR)-based metabonomic techniques. Prenatal nicotine exposure caused noticeably lower body weights, higher IUGR rates of fetal rats, and elevated maternal and fetal corticosterone (CORT) levels compared to the controls. The correlation analysis among maternal, fetal serum CORT levels and fetal bodyweight suggested that the levels of maternal and fetal serum CORT presented a positive correlation (r=0.356, n=32, P<0.05), while there was a negative correlation between fetal (r=-0.639, n=32, P<0.01) and maternal (r=-0.530, n=32, P<0.01) serum CORT level and fetal bodyweight. The fetal metabonome alterations included the stimulation of lipogenesis and the decreased levels of glucose and amino acids. The maternal metabonome alterations involved the enhanced blood glucose levels, fatty acid oxygenolysis, proteolysis and amino acid accumulation. These results suggested that prenatal nicotine exposure is associated with an altered maternal and fetal metabonome, which may be related to maternal increased glucocorticoid level induced by nicotine. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Binge-Like Ethanol Consumption Increases Corticosterone Levels and Neurodegneration whereas occupancy of Type II Glucocorticoid Receptors with Mifepristone is Neuroprotective

PubMed Central

Cippitelli, Andrea; Damadzic, Ruslan; Hamelink, Carol; Brunnquell, Michael; Thorsell, Annika; Heilig, Markus; Eskay, Robert L

2012-01-01

Excessive ethanol (EtOH) use leads to impaired memory and cognition. Using a rat model of binge-like intoxication, we tested whether elevated corticosterone (Cort) levels contribute to the neurotoxic consequences of EtOH exposure. Rats were adrenalectomized (Adx) and implanted with cholesterol pellets, or cholesterol pellets containing basal, medium or high Cort. Intragastric EtOH or an isocaloric control solution was given 3 times daily for 4 days to achieve blood alcohol levels (BALs) ranging between 200-350 mg/dl. Mean 24 hour (24-hr) plasma Cort levels were ~110 ng/ml and ~40 ng/ml in intact EtOH treated and intact control, respectively. Basal Cort replacement in EtOH-treated Adx animals animals did not exacerbate alcohol-induced neurodegeneration in the hippocampal dentate gyrus (DG) or the entorhinal cortex (EC) as observed by amino-cupric silver staining. In contrast, Cort replacement resulting in levels 2-fold higher (medium) than normal, or higher (high) in Adx-Cort-EtOH animals increased neurodegeneration. In separate experiments, pharmacological blockade of the Type II glucocortocoid (GC) receptor was initiated with mifepristone (RU38486; 0, 5, 15 mg/kg/day, i.p.). At the higher dose, mifepristone decreased the number of degenerating hippocampal DG cells in binge-EtOH treated intact animals, whereas, only a trend for reduction was observed in 15 mg/kg/day mifepristone treated animals in the EC, as determined by Fluoro Jade B staining. These results suggest that Cort in part mediates EtOH-induced neurotoxicity in the brain through activation of Type II GC receptors. PMID:22500955

Individual variation in baseline and stress-induced corticosterone and prolactin levels predicts parental effort by nesting mourning doves

USGS Publications Warehouse

Miller, David A.; Vleck, Carol M.; Otis, David L.

2009-01-01

Endocrine systems have an important mechanistic role in structuring life-history trade-offs. During breeding, individual variation in prolactin (PRL) and corticosterone (CORT) levels affects behavioral and physiological processes that drive trade-offs between reproduction and self-maintenance. We examined patterns in baseline (BL) and stress induced (SI; level following a standard capture-restraint protocol) levels of PRL and CORT for breeding mourning doves (Zenaida macroura). We determined whether the relationship of adult condition and parental effort to hormone levels in wild birds was consistent with life-history predictions. Both BL PRL and BL CORT level in adults were positively related to nestling weight at early nestling ages, consistent with the prediction of a positive relationship of hormone levels to current parental effort of adults and associated increased energy demand. Results are consistent with the two hormones acting together at baseline levels to limit negative effects of CORT on reproduction while maintaining beneficial effects such as increased foraging for nestling feeding. Our data did not support predictions that SI responses would vary in response to nestling or adult condition. The magnitude of CORT response in the parents to our capture-restraint protocol was negatively correlated with subsequent parental effort. Average nestling weights for adults with the highest SI CORT response were on average 10–15% lighter than expected for their age in follow-up visits after the stress event. Our results demonstrated a relationship between individual hormone levels and within population variation in parental effort and suggested that hormonal control plays an important role in structuring reproductive decisions for mourning doves.

Individual variation in baseline and stress-induced corticosterone and prolactin levels predicts parental effort by nesting mourning doves

USGS Publications Warehouse

Miller, David A.; Vleck, Carol M.; Otis, David L.

2009-01-01

Endocrine systems have an important mechanistic role in structuring life-history trade-offs. During breeding, individual variation in prolactin (PRL) and corticosterone (CORT) levels affects behavioral and physiological processes that drive trade-offs between reproduction and self-maintenance. We examined patterns in baseline (BL) and stress induced (SI; level following a standard capture-restraint protocol) levels of PRL and CORT for breeding mourning doves (Zenaida macroura). We determined whether the relationship of adult condition and parental effort to hormone levels in wild birds was consistent with life-history predictions. Both BL PRL and BL CORT level in adults were positively related to nestling weight at early nestling ages, consistent with the prediction of a positive relationship of hormone levels to current parental effort of adults and associated increased energy demand. Results are consistent with the two hormones acting together at baseline levels to limit negative effects of CORT on reproduction while maintaining beneficial effects such as increased foraging for nestling feeding. Our data did not support predictions that SI responses would vary in response to nestling or adult condition. The magnitude of CORT response in the parents to our capture-restraint protocol was negatively correlated with subsequent parental effort. Average nestling weights for adults with the highest SI CORT response were on average 10–15% lighter than expected for their age in follow-up visits after the stress event. Our results demonstrated a relationship between individual hormone levels and within population variation in parental effort and suggested that hormonal control plays an important role in structuring reproductive decisions for mourning doves.

Transient increase in alcohol self-administration following a period of chronic exposure to corticosterone

PubMed Central

Besheer, Joyce; Fisher, Kristen R.; Lindsay, Tessa G.; Cannady, Reginald

2013-01-01

Stressful life events and chronic stressors have been associated with escalations in alcohol drinking. Stress exposure leads to the secretion of glucocorticoids (cortisol in the human; corticosterone (CORT) in the rodent). To model a period of heightened elevations in CORT, the present work assessed the effects of chronic exposure to the stress hormone CORT on alcohol self-administration. Male Long Evans rats were trained to self-administer a sweetened alcohol solution (2% sucrose/15% alcohol) resulting in moderate levels of daily alcohol intake (0.5–0.7 g/kg). Following stable baseline operant self-administration, rats received CORT in the drinking water for 7 days. A transient increase in alcohol self-administration was observed on the first self-administration session following CORT exposure, and behavior returned to control levels by the second session. Control experiments determined that this increase in alcohol self-administration was specific to alcohol, unrelated to general motor activation, and functionally dissociated from decreased CORT levels at the time of testing. These results indicate that repeated exposure to heightened levels of stress hormone (e.g., as may be experienced during stressful episodes) has the potential to lead to exacerbated alcohol intake in low to moderate drinkers. Given that maladaptive drinking patterns, such as escalated alcohol drinking following stressful episodes, have the potential to put an individual at risk for future drinking disorders, utilization of this model will be important for examination of neuroadaptations that occur as a consequence of CORT exposure in order to better understand escalated drinking following stressful episodes in nondependent individuals. PMID:23643750

Voluntary Wheel Running Reverses the Decrease in Subventricular Zone Neurogenesis Caused by Corticosterone.

PubMed

Lee, Jada Chia-Di; Yau, Suk-Yu; Lee, Tatia M C; Lau, Benson Wui-Man; So, Kwok-Fai

2016-11-01

Adult neurogenesis within the dentate gyrus (DG) of the hippocampus can be increased by voluntary exercise but is suppressed under stress, such as with corticosterone (CORT). However, the effects of exercise and CORT on the cell proliferation of the other traditional neurogenic site, the subventricular zone (SVZ), have been reported with controversial results. In addition, the cotreatment effects of voluntary exercise and CORT have not been investigated. This study aims to determine whether CORT can suppress cell proliferation in the SVZ and whether this can be reversed by voluntary exercise. In the present study, the effect of chronic (4 weeks) CORT treatment and wheel running simultaneously on the SVZ cell proliferation of adult Sprague-Dawley rats was examined. The results showed that cell proliferation indicated by bromodeoxyuridine (BrdU) was increased by voluntary wheel running, whereas it was decreased by CORT treatment within the SVZ of the rats without running. For the rats with both CORT treatment and wheel running, it was found that the number of BrdU-labeled cells was approximately at the same level as the vehicle control group. Furthermore, these proliferating cells expressed doublecortin (DCX), a migrating neuroblast marker. Wheel running increased the percentage of BrdU-labeled cells expressing DCX in the SVZ, whereas CORT treatment decreased this percentage. Thus, chronic injection of CORT can decrease the number of proliferating cells, while wheel running can reverse the decrease in cell proliferation within the SVZ to normal levels. In addition, CORT can suppress the cell differentiation within the SVZ, and this was alleviated by wheel running as indicated by the double labeling of BrdU and DCX.

Hypothalamic-pituitary-adrenal (HPA) axis function in the California mouse (Peromyscus californicus): Changes in baseline activity, reactivity, and fecal excretion of glucocorticoids across the diurnal cycle

PubMed Central

Harris, Breanna N.; Saltzman, Wendy; de Jong, Trynke R.; Milnes, Matthew R.

2012-01-01

The California mouse, Peromyscus californicus, is an increasingly popular animal model in behavioral, neural, and endocrine studies, but little is known about its baseline hypothalamicpituitary-adrenal (HPA) axis activity or HPA responses to stressors. We characterized plasma corticosterone (CORT) concentrations in P. californicus under baseline conditions across the diurnal cycle, in response to pharmacological manipulation of the HPA axis, and in response to a variety of stressors at different times of day. In addition, we explored the use of fecal samples to monitor adrenocortical activity non-invasively. California mice have very high baseline levels of circulating CORT that change markedly over 24 hours, but that do not differ between the sexes. This species may be somewhat glucocorticoid-resistant in comparison to other rodents as a relatively high dose of dexamethasone (5 mg/kg, s.c.) was required to suppress plasma CORT for 8 h post-injection. CORT responses to stressors and ACTH injection differed with time of day, as CORT concentrations were elevated more readily during the morning (inactive period) than in the evening (active period) when compared to time-matched control. Data from 3H-CORT injection studies show that the time course for excretion of fecal CORT, or glucocorticoid metabolites, differs with time of injection. Mice injected in the evening excreted the majority of fecal radioactivity 2–4 h post-injection whereas mice injected during the morning did so at 14–16 h post-injection. Unfortunately, the antibody we used does not adequately bind the most prevalent fecal glucocorticoid metabolites and therefore we could not validate its use for fecal assays. PMID:23026495

Elevated stress hormone diminishes the strength of female preferences for acoustic signals in the green treefrog.

PubMed

Davis, A Gabriell; Leary, Christopher J

2015-03-01

Mate selection can be stressful; time spent searching for mates can increase predation risk and/or decrease food consumption, resulting in elevated stress hormone levels. Both high predation risk and low food availability are often associated with increased variation in mate choice by females, but it is not clear whether stress hormone levels contribute to such variation in female behavior. We examined how the stress hormone corticosterone (CORT) affects female preferences for acoustic signals in the green treefrog, Hyla cinerea. Specifically, we assessed whether CORT administration affects female preferences for call rate - an acoustic feature that is typically under directional selection via mate choice by females in most anurans and other species that communicate using acoustic signals. Using a dual speaker playback paradigm, we show that females that were administered higher doses of CORT were less likely to choose male advertisement calls broadcast at high rates. Neither CORT dose nor level was related to the latency of female phonotactic responses, suggesting that elevated CORT does not influence the motivation to mate. Results were also not related to circulating sex steroids (i.e., progesterone, androgens or estradiol) that have traditionally been the focus of studies examining the hormonal basis for variation in female mate choice. Our results thus indicate that elevated CORT levels decrease the strength of female preferences for acoustic signals. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress hormone is implicated in satellite-caller associations and sexual selection in the Great Plains toad.

PubMed

Leary, Christopher J; Garcia, Apryl M; Knapp, Rosemary

2006-10-01

The effects of androgens on male-typical traits suggest that variation among males in circulating levels can play a major role in sexual selection. We examined whether variation in vocal attractiveness is attributable to differences in androgen levels among Great Plains toads (Bufo cognatus). We found that noncalling "satellite" males practicing an alternative mating tactic were more likely to associate with males producing long calls. However, callers with satellites did not have higher androgen levels than callers without satellites. Rather, callers with satellites had significantly lower corticosterone (CORT) levels than callers without satellites. A CORT manipulation experiment suggested that differences in calls for males with and without satellites were related to differences in CORT levels. Furthermore, there was a negative correlation between CORT level and call duration within most nights of chorus activity. However, the correlation was weak for the pooled data (across all nights), suggesting that local environmental and/or social factors also affect call duration. Last, we show that females preferred broadcast calls of longer duration, characteristic of males with satellites and low CORT. These results imply that satellites optimize their reproductive success by associating with males producing long calls. However, this association should negatively affect the fitness of attractive callers.

Feather corticosterone levels are related to age and future body condition, but not to subsequent fitness, in a declining migratory songbird.

PubMed

Boves, Than J; Fairhurst, Graham D; Rushing, Clark S; Buehler, David A

2016-01-01

In migratory species, breeding and non-breeding locations are geographically separate, yet the effects of conditions from one stage may carry over to affect a subsequent stage. Ideally, to understand the mechanisms and implications of 'carry-over effects', one would need to follow individuals throughout the year, quantify potential environmental causal factors and physiological mediators during multiple life-history stages, and measure downstream fitness. Owing to current limitations of tracking technology, this is impossible for small, long-distance migrants, so indirect methods to characterize carry-over effects are required. Corticosterone (CORT) is a suspected physiological mediator of carry-over effects, but when collected from blood it provides only a physiological snapshot at that point in time. When extracted from feathers, however, feather corticosterone (CORT f ) provides a measure of responses to stressors from previous, and longer, time periods. We collected feathers grown during two life-history stages (post-breeding and subsequent wintering) from individuals of two age classes of a rapidly declining migratory songbird, the cerulean warbler ( Setophaga cerulea ), on their breeding grounds and quantified CORT f concentrations. We then monitored reproduction and survival of individuals and analysed relationships among CORT f and age, body condition and future fitness. Compared with older males, second-year males had higher CORT f concentrations during both stages. When controlling for age and year, body condition at capture was positively related to CORT f concentrations from winter (especially for older birds). However, we found no relationships between CORT f and fitness (as defined by reproduction and survival). Thus, elevated CORT may represent a beneficial physiological response (e.g. hyperphagia prior to migration), particularly for certain life-history stages, and may mediate the condition in which individuals transition between stages. But for those birds that survive migration, subsequent fitness is likely determined by more recent events and local conditions (i.e. on breeding grounds), which have the potential to counteract conditions from the winter.

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels

PubMed Central

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Background: Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Materials and Methods: Forty male rats were randomly allocated to five different groups (n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results: Results revealed that chronic stress had a significantly (P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly (P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly (P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly (P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. Conclusions: It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain. PMID:29387668

Effects of Crocin on Learning and Memory in Rats Under Chronic Restraint Stress with Special Focus on the Hippocampal and Frontal Cortex Corticosterone Levels.

PubMed

Dastgerdi, Azadehalsadat Hosseini; Radahmadi, Maryam; Pourshanazari, Ali Asghar; Dastgerdi, Hajaralsadat Hosseini

2017-01-01

Chronic stress adversely influences brain functions while crocin, as an effective component of saffron, exhibits positive effects on memory processes. This study investigated the effects of different doses of crocin on the improvement of learning and memory as well as corticosterone (CORT) levels in the hippocampus and frontal cortex of rats subjected to chronic stress. Forty male rats were randomly allocated to five different groups ( n = 8): Control, sham; stress (6 h/day for 21 days) groups, and two groups receiving daily intraperitoneal injections of one of two doses (30 and 60 mg/kg) of crocin accompanied by 21 days of restraint stress. Latency was evaluated as a brain function using the passive avoidance test before and one-day after a foot shock. CORT levels were measured in the homogenized hippocampus and frontal cortex. Results revealed that chronic stress had a significantly ( P < 0.01) negative effect on memory. Crocin (30 and 60 mg/kg), however, gave increase to significantly ( P < 0.01 and P < 0.05; respectively) improved memory functions in the stressed rats. Furthermore, the CORT levels in the hippocampus and frontal cortex declined significantly ( P < 0.05) in the stress group compared to the control. Only a crocin dose of 30 mg/kg was observed modulate significantly ( P < 0.05) the CORT levels in the hippocampus and frontal cortex in the stressed group. It was found that the lower crocin dose (30 mg/kg) had more beneficial effects than its higher (60 mg/kg) dose on learning and memory under chronic stress conditions. Moreover, it was speculated that different doses of crocin act on different neurotransmitters and biochemical factors in the brain.

Cytosolic glucocorticoid receptor in the testis of Bufo arenarum: seasonal changes in its binding parameters.

PubMed

Denari, Daniela; Ceballos, Nora R

2006-07-01

Glucocorticoids (GC) are the hormonal mediators of stress. In mammals, high levels of GC have negative effects on reproductive physiology. For instance, GC can inhibit testicular testosterone synthesis by acting via glucocorticoid receptors (GR), the extent of the inhibition being dependent on GC levels. However, the effect of GC on testicular function and even the presence of GR in amphibians are still unclear. The purpose of this work was to characterise testicular cytosolic GR in Bufo arenarum, determining the seasonal changes in its binding parameters as well as the intratesticular localisation. The binding assays were performed in testis cytosol with [3H]dexamethasone (DEX) and [3H]corticosterone (CORT). Binding kinetics of DEX and CORT fitted to a one-site model. Results were expressed as means +/- standard error. Apparent number of binding sites (Bapp) was similar for both steroids (Bapp DEX = 352.53 +/- 72.08 fmol/mg protein; Bapp CORT = 454.24 +/- 134.97 fmol/mg protein) suggesting that both hormones bind to the same site. Competition studies with different steroids showed that the order of displacement of [3H]DEX and [3H]CORT specific binding is: DEX approximately RU486 approximately deoxycorticosterone (DOC) > CORT > aldosterone > RU28362 > progesterone > 11-dehydroCORT. The affinity of GR for DEX (Kd = 11.2 +/- 1.5 nM) remained constant throughout the year while circulating CORT clearly increased during the reproductive season. Therefore, testis sensitivity to GC action would depend mainly on inactivating mechanisms (11beta-hydroxysteroid dehydrogenase type 2) and CORT plasma levels. Since total and free CORT are higher in the reproductive than in the non-reproductive period, the magnitude of GC actions could be higher during the breeding season. The intratesticular localisation of the GR was determined after separation of cells by a Percoll density gradient followed by binding assays in each fraction. DEX binds to two different fractions corresponding to Leydig and Sertoli cells. In conclusion, in the testis of B. arenarum GC could regulate the function of both cellular types particularly during breeding when CORT reaches the highest plasma concentration.

Impact of transportation duration on stress responses in day-old chicks from young and old breeders.

PubMed

Jacobs, Leonie; Delezie, Evelyne; Duchateau, Luc; Goethals, Klara; Ampe, Bart; Buyse, Johan; Tuyttens, Frank Andre Maurice

2017-06-01

The aim of this study was to assess the interaction effect of transportation duration and parental age on physiological stress responses and quality in day-old chicks. After hatch, 3240 chicks from either 29-week old (young) or 60-week old (old) broiler breeders were transported for 1.5h (short) or 11h (long). Thereafter, 228 chicks were assessed for quality and blood plasma was assayed for corticosterone (CORT), lactate, glucose, and thiobarbituric acid-reactive substances (TBARS, increased concentrations can indicate oxidative stress). No interaction effects of parental age and transportation duration were found (all P>0.10). Chicks from young breeders showed higher CORT levels (P=0.007) and were of higher quality (Tona method, P<0.001) than those from old breeders. After long transportation, chicks showed increased CORT (P<0.001) and lower TBARS levels (P<0.001) compared to after short transportation. No evidence was provided that long transportation differently affected the quality or stress responses of chicks from breeder flocks of two ages. Copyright © 2017. Published by Elsevier Ltd.

Delayed suppression of hippocampal cell proliferation in rats following inescapable shocks.

PubMed

Fornal, Casimir A; Stevens, Joanne; Barson, Jessica R; Blakley, Gregory G; Patterson-Buckendahl, Patricia; Jacobs, Barry L

2007-01-26

Adult Sprague-Dawley rats were exposed to a single session of 100 inescapable tail shocks (IS). Bromodeoxyuridine (BrdU) was administered 1 h, 2 days or 7 days later and hippocampal cell proliferation (CP) was assessed after a 2-h survival period. Measures of plasma corticosterone (CORT) levels were also obtained. Despite a large increase in CORT immediately following IS, no associated change in CP was observed. In fact, the only significant change in CP was seen 7 days after IS, at a time when CORT was unchanged from control levels. These data raise questions about the general nature of the relationship between CORT and CP. They also suggest that, under some conditions, changes in hippocampal CP may emerge only after an "incubation period".

Chronic corticosterone administration reduces dendritic complexity in mature, but not young granule cells in the rat dentate gyrus.

PubMed

Yau, Suk-Yu; Li, Ang; Tong, Jian-Bin; Bostrom, Crystal; Christie, Brian R; Lee, Tatia M C; So, Kwok-Fai

2016-09-21

Our previous work has shown that exposure to the stress hormone corticosterone (40 mg/kg CORT) for two weeks induces dendritic atrophy of pyramidal neurons in the hippocampal CA3 region and behavioral deficits. However, it is unclear whether this treatment also affects the dentate gyrus (DG), a subregion of the hippocampus comprising a heterogeneous population of young and mature neurons. We examined the effect of CORT treatment on the dendritic complexity of mature and young granule cells in the DG. We utilized a Golgi staining method to investigate the dendritic morphology and spine density of young neurons in the inner granular cell layer (GCL) and mature neurons in the outer GCL in response to CORT application. The expressions of glucocorticoid receptors during neuronal maturation were examined using Western blot analysis in a primary hippocampal neuronal culture. Sholl analysis revealed that CORT treatment decreased the number of intersections and shortened the dendritic length in mature, but not young, granule cells. However, the spine density of mature and young neurons was not affected. Western blot analysis showed a progressive increase in the protein levels of glucocorticoid receptors (GRs) in the cultured primary hippocampal neurons during neuronal maturation. These data suggest that mature neurons are likely more vulnerable to chronic exposure to CORT; this may be due to their higher expression of GRs when compared to younger DG neurons.

Corticosterone response to the plus-maze: high correlation with risk assessment in rats and mice.

PubMed

Rodgers, R J; Haller, J; Holmes, A; Halasz, J; Walton, T J; Brain, P F

Exposure to the elevated plus-maze induces behavioural and physiological effects in rodents consistent with fear/anxiety. Maze-naive animals display high levels of risk assessment towards the open arms, and explore these areas less extensively than other parts of the maze while, immediately following the test, pain latencies, skin conductance levels, and plasma corticosterone titres (CORT) are significantly elevated. Although previous research has suggested a link between the plasma CORT response and open-arm exploration, significant elevations in CORT have also been found with restricted exposure to the closed arms. The present study employed ethological measures in an attempt to further characterise the relationship between behavioural and CORT responses to this widely used animal model of anxiety. Our results confirm that, relative to home-cage controls, 5-min exposure to the plus-maze significantly increases plasma CORT levels in test-naive male Wistar rats and male Swiss-Webster mice. Furthermore, in both species, the CORT response was found to be highly correlated with measures of risk assessment (mice: rs = +0.87; rats: rs = +0.58), but not with measures of open-arm activity (entries, time), general locomotor activity, rearing, or head dipping. Findings are discussed in relation to the functional significance of risk assessment in potentially dangerous situations and the potential involvement of glucocorticoids in this process. All rights reserved.

Chronic social instability increases anxiety-like behavior and ethanol preference in male Long Evans rats.

PubMed

Roeckner, Alyssa R; Bowling, Alexandra; Butler, Tracy R

2017-05-01

Chronic stress during adolescence is related to increased prevalence of anxiety disorders and alcohol use disorders in humans. This phenotype has been consistently recapitulated in animal models with male subjects, but models using female subjects are fewer. The aim of these studies was to test the hypothesis that chronic social instability (CSI) during adolescence engenders increased anxiety-like behavior, increased corticosterone, and greater ethanol intake and/or preference than control groups in male and female rats. A chronic social instability (CSI) procedure was conducted in separate cohorts of female and male adolescent Long Evans rats. CSI included daily social isolation for 1h, and then pair housing with a novel cage mate for 23h until the next 1h isolation period from PND 30-46. Control groups included social stability (SS), chronic isolation (ISO), and acute social instability (aSI). At PND 49-50, anxiety-like behavior was assessed on the elevated plus maze, and on PND 51 tails bloods were obtained for determination of corticosterone (CORT) levels. This was followed by 4weeks of ethanol drinking in a home cage intermittent access ethanol drinking paradigm (PND 55-81 for males, PND 57-83 for females). Planned contrast testing showed that the male CSI group had greater anxiety-like behavior compared controls, but group differences were not apparent for CORT. CSI males had significantly higher levels of ethanol preference during drinking weeks 2-3 compared to all other groups and compared to SS and ISO groups in week 4. For the female cohort, we did not observe consistent group differences in anxiety-like behavior, CORT levels were unexpectedly lower in the ISO group only compared to the other groups, and group differences were not apparent for ethanol intake/preference. In conclusion, chronic stress during adolescence in the form of social instability increases anxiety-like behavior and ethanol preference in male rats, consistent with other models of chronic stress during adolescence. Conversely, and contrary to our hypothesis, female rats' anxiety-like behavior, CORT level, and ethanol intake/preference were not altered by CSI. New paradigms must continue to be explored for study of clinically relevant relationships in female preclinical models. Copyright © 2017 Elsevier Inc. All rights reserved.

Do wild-caught urban house sparrows show desensitized stress responses to a novel stressor?

PubMed

Salleh Hudin, Noraine; Teyssier, Aimeric; Aerts, Johan; Fairhurst, Graham D; Strubbe, Diederik; White, Joël; De Neve, Liesbeth; Lens, Luc

2018-04-09

While urbanisation exposes individuals to novel challenges, urban areas may also constitute stable environments in which seasonal fluctuations are buffered. Baseline and stress-induced plasma corticosterone levels are often found to be similar in urban and rural populations. Here we aimed to disentangle two possible mechanisms underlying such pattern: (i) urban environments are no more stressful or urban birds have a better ability to habituate to stressors; or (ii) urban birds developed desensitized stress responses. We exposed wild-caught urban and rural house sparrows ( Passer domesticus ) to combined captivity and diet treatments (urban vs rural diet) and measured corticosterone levels (cort f ) both in natural tail feathers and in regrown homologous ones. Urban and rural house sparrows showed similar cort f levels in the wild and in response to novel stressors caused by the experiment, supporting the growing notion that urban environments are no more stressful during the non-breeding season than are rural ones. Still, juveniles and males originating from urban populations showed the highest cort f levels in regrown feathers. We did not find evidence that cort f was consistent within individuals across moults. Our study stresses the need for incorporating both intrinsic and environmental factors for the interpretation of variation in cort f between populations. © 2018. Published by The Company of Biologists Ltd.

Diurnal Corticosterone Presence and Phase Modulate Clock Gene Expression in the Male Rat Prefrontal Cortex

PubMed Central

Chun, Lauren E.; Hinds, Laura R.; Spencer, Robert L.

2016-01-01

Mood disorders are associated with dysregulation of prefrontal cortex (PFC) function, circadian rhythms, and diurnal glucocorticoid (corticosterone [CORT]) circulation. Entrainment of clock gene expression in some peripheral tissues depends on CORT. In this study, we characterized over the course of the day the mRNA expression pattern of the core clock genes Per1, Per2, and Bmal1 in the male rat PFC and suprachiasmatic nucleus (SCN) under different diurnal CORT conditions. In experiment 1, rats were left adrenal-intact (sham) or were adrenalectomized (ADX) followed by 10 daily antiphasic (opposite time of day of the endogenous CORT peak) ip injections of either vehicle or 2.5 mg/kg CORT. In experiment 2, all rats received ADX surgery followed by 13 daily injections of vehicle or CORT either antiphasic or in-phase with the endogenous CORT peak. In sham rats clock gene mRNA levels displayed a diurnal pattern of expression in the PFC and the SCN, but the phase differed between the 2 structures. ADX substantially altered clock gene expression patterns in the PFC. This alteration was normalized by in-phase CORT treatment, whereas antiphasic CORT treatment appears to have eliminated a diurnal pattern (Per1 and Bmal1) or dampened/inverted its phase (Per2). There was very little effect of CORT condition on clock gene expression in the SCN. These experiments suggest that an important component of glucocorticoid circadian physiology entails CORT regulation of the molecular clock in the PFC. Consequently, they also point to a possible mechanism that contributes to PFC disrupted function in disorders associated with abnormal CORT circulation. PMID:26901093

Serotonin and corticosterone rhythms in mice exposed to cigarette smoke and in patients with COPD: implication for COPD-associated neuropathogenesis.

PubMed

Sundar, Isaac K; Yao, Hongwei; Huang, Yadi; Lyda, Elizabeth; Sime, Patricia J; Sellix, Michael T; Rahman, Irfan

2014-01-01

The circadian timing system controls daily rhythms of physiology and behavior, and disruption of clock function can trigger stressful life events. Daily exposure to cigarette smoke (CS) can lead to alteration in diverse biological and physiological processes. Smoking is associated with mood disorders, including depression and anxiety. Patients with chronic obstructive pulmonary disease (COPD) have abnormal circadian rhythms, reflected by daily changes in respiratory symptoms and lung function. Corticosterone (CORT) is an adrenal steroid that plays a considerable role in stress and anti-inflammatory responses. Serotonin (5-hydroxytryptamine; 5HT) is a neurohormone, which plays a role in sleep/wake regulation and affective disorders. Secretion of stress hormones (CORT and 5HT) is under the control of the circadian clock in the suprachiasmatic nucleus. Since smoking is a contributing factor in the development of COPD, we hypothesize that CS can affect circadian rhythms of CORT and 5HT secretion leading to sleep and mood disorders in smokers and patients with COPD. We measured the daily rhythms of plasma CORT and 5HT in mice following acute (3 d), sub-chronic (10 d) or chronic (6 mo) CS exposure and in plasma from non-smokers, smokers and patients with COPD. Acute and chronic CS exposure affected both the timing (peak phase) and amplitude of the daily rhythm of plasma CORT and 5HT in mice. Acute CS appeared to have subtle time-dependent effects on CORT levels but more pronounced effects on 5HT. As compared with CORT, plasma 5HT was slightly elevated in smokers but was reduced in patients with COPD. Thus, the effects of CS on plasma 5HT were consistent between mice and patients with COPD. Together, these data reveal a significant impact of CS exposure on rhythms of stress hormone secretion and subsequent detrimental effects on cognitive function, depression-like behavior, mood/anxiety and sleep quality in smokers and patients with COPD.

Influence of corticosterone treatment on nestling begging in Florida scrub-jays (Aphelocoma coerulescens).

PubMed

Elderbrock, Emily K; Small, Thomas W; Schoech, Stephan J

2018-04-01

Altricial young are dependent on adults for protection and food, and they display nutritional need by begging to elicit feeding from parents. Begging at high levels can be energetically expensive and attract predators; thus, an individual must balance its nutritional needs with these potential costs. Further, because a parent is limited in the amount of food it can provide, begging can contribute to both parent-offspring conflict and sibling-sibling competition. Many extrinsic and intrinsic factors may contribute to begging behavior. One intrinsic factor of interest is corticosterone (CORT), a metabolic hormone hypothesized to play a role in regulating a nestling's begging behavior. We investigated the hypothesis that increased exposure to CORT influences nestling begging behavior in an altricial species, the Florida scrub-jay (Aphelocoma coerulescens). We treated one nestling per treatment nest with a twice-daily dose of exogenous hormone via a CORT-injected waxworm, whereas a second individual received a vehicle-injected waxworm. We monitored individual nestling and adult behavior at all nests with the use of high-definition video cameras on several days during treatment. We found no difference in begging rate between CORT fed and vehicle fed nestlings within a treatment nest. Further, to determine whether CORT treatment had indirect effects on the entire brood, we monitored additional nests, in which nestlings were not manipulated. When treatment and controls were compared, overall begging rates of nestlings in treatment nests were greater than those in control nests. This result suggests that CORT treatment of an individual altered its behavior, as well as that of its siblings. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of Schisandra chinensis on interleukins, glucose metabolism, and pituitary-adrenal and gonadal axis in rats under strenuous swimming exercise.

PubMed

Li, Jie; Wang, Jian; Shao, Jia-Qing; Du, Hong; Wang, Yang-Tian; Peng, Li

2015-01-01

To investigate the effect of Chinese medicine (CM) Schisandra chinensis on interleukin (IL), glucose metabolism, and pituitary-adrenal and gonadal axis of rats after strenuous navigation and exercise. A total of 45 Sprague-Dawley rats were randomized into the quiet control group, the stress group, and the CM group (15 in each group). The CM group received 2.5 g/kg of Schisandra chinensis twice per day for one week before modeling. Except the quiet controls, rats were trained using the Bedford mode for 10 days. On the 11th day, they performed 3 h of stressful experimental navigation and 3 h of strenuous treadmill exercise. The levels of serum testosterone (T), cortisol (CORT), luteinizing hormone (LH), IL-1, IL-2, and IL-6 were tested by radioimmunoassay and enzyme-linked immunosorbent assay, respectively. The adrenal cortex ultrastructure was observed using electron microscopy. Compared with the quiet control group, after navigation and strenuous exercise, blood glucose was increased, and T level was decreased in the stress group (both P<0.01). The blood glucose, CORT, IL-1 and IL-2 levels were significantly reduced in the CM group (P<0.05 or P<0.01) as compared with the stress group. Electron microscopy revealed that the rats in the CM group had a smaller decrease in adrenal intracellular lipid droplets and higher levels of apoptosis than those in the stress group. Schisandra chinensis can reduce serum CORT and blood glucose levels in stressed rats. It appears to protect the cell structure of the adrenal cortex, and offset the negative effects of psychological stress and strenuous exercise related to immune dysfunction. Schisandra chinensis plays a regulatory role in immune function, and can decrease the influence of stress in rats.

Resveratrol ameliorates depressive-like behavior in repeated corticosterone-induced depression in mice.

PubMed

Ali, Syed Hamid; Madhana, Rajaram Mohanrao; K V, Athira; Kasala, Eshvendar Reddy; Bodduluru, Lakshmi Narendra; Pitta, Sathish; Mahareddy, Jalandhar Reddy; Lahkar, Mangala

2015-09-01

A mouse model of depression has been recently developed by exogenous corticosterone (CORT) administration, which has shown to mimic HPA-axis induced depression-like state in animals. The present study aimed to examine the antidepressant-like effect and the possible mechanisms of resveratrol, a naturally occurring polyphenol of phytoalexin family, on depressive-like behavior induced by repeated corticosterone injections in mice. Mice were injected subcutaneously (s.c.) with 40mg/kg corticosterone (CORT) chronically for 21days. Resveratrol and fluoxetine were administered 30min prior to the CORT injection. After 21-days treatment with respective drugs, behavioral and biochemical parameters were estimated. Since brain derived neurotrophic factor (BDNF) has been implicated in antidepressant activity of many drugs, we also evaluated the effect of resveratrol on BDNF in the hippocampus. Three weeks of CORT injections in mice resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test and tail suspension test. Further, there was a significant increase in serum corticosterone level and a significant decrease in hippocampus BDNF level in CORT-treated mice. Treatment of mice with resveratrol significantly ameliorated all the behavioral and biochemical changes induced by corticosterone. These results suggest that resveratrol produces an antidepressant-like effect in CORT-induced depression in mice, which is possibly mediated by rectifying the stress-based hypothalamic-pituitary-adrenal (HPA) axis dysfunction paradigm and upregulation of hippocampal BDNF levels. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain antioxidant effect of mirtazapine and reversal of sedation by its combination with alpha-lipoic acid in a model of depression induced by corticosterone.

PubMed

Oliveira, Tatiana de Queiroz; de Sousa, Caren Nádia Soares; Vasconcelos, Germana Silva; de Sousa, Luciene Costa; de Oliveira, Anneheydi Araújo; Patrocínio, Cláudio Felipe Vasconcelos; Medeiros, Ingridy da Silva; Honório Júnior, José Eduardo Ribeiro; Maes, Michael; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

2017-09-01

Depression is accompanied by activated neuro-oxidative and neuro-nitrosative pathways, while targeting these pathways has clinical efficacy in depression. This study aimed to investigate the effects of mirtazapine (MIRT) alone and combined with alpha-lipoic acid (ALA) against corticosterone (CORT) induced behavioral and oxidative alterations. Male mice received vehicle or CORT 20mg/kg during 14 days. From the 15th to 21st days they were divided in groups administered: vehicle, MIRT 3mg/kg or the combinations MIRT+ALA100 or MIRT+ALA200. On the 21st day of treatment, the animals were subjected to behavioral tests. Twenty-four hours after the last drug administration hippocampus (HC) and striatum (ST) were dissected for the determination reduced glutathione (GSH), lipid peroxidation (LP) and nitrite levels. CORT induced anxiety- and depressive-like behaviors as observed by increased immobility time in the tail suspension test and decreased sucrose consumption. MIRT or MIRT+ALA are effective in reversing anxiety- and depressive-like behaviors induced by CORT. CORT and MIRT alone prolonged sleeping time and this effect was reversed by MIRT+ALA. CORT significantly increased LP, which was reversed by MIRT or MIRT+ALA. Nitrite levels were increased in CORT-treated animals and reversed by MIRT+ALA200 (HC), MIRT or MIRT+ALA (ST). A relative small sample size and lack of a washout period between drug administration and behavioral testing. MIRT or MIRT+ALA reverse CORT-induced anxiety- and depressive-like behaviors probably via their central antioxidant effects. Augmentation of MIRT with ALA may reverse sedation, an important side effect of MIRT. Randomized controlled studies are needed to examine the clinical efficacy of this combination in human depression. Copyright © 2017 Elsevier B.V. All rights reserved.

Chronic glucocorticoid exposure-induced epididymal adiposity is associated with mitochondrial dysfunction in white adipose tissue of male C57BL/6J mice.

PubMed

Yu, Jie; Yu, Bing; He, Jun; Zheng, Ping; Mao, Xiangbing; Han, Guoquan; Chen, Daiwen

2014-01-01

Prolonged and excessive glucocorticoids (GC) exposure resulted from Cushing's syndrome or GC therapy develops central obesity. Moreover, mitochondria are crucial in adipose energy homeostasis. Thus, we tested the hypothesis that mitochondrial dysfunction may contribute to chronic GC exposure-induced epididymal adiposity in the present study. A total of thirty-six 5-week-old male C57BL/6J mice (∼20 g) were administrated with 100 µg/ml corticosterone (CORT) or vehicle through drinking water for 4 weeks. Chronic CORT exposure mildly decreased body weight without altering food and water intake in mice. The epididymal fat accumulation was increased, but adipocyte size was decreased by CORT. CORT also increased plasma CORT, insulin, leptin, and fibroblast growth factor 21 concentrations as measured by RIA or ELISA. Interestingly, CORT increased plasma levels of triacylglycerols and nonesterified fatty acids, and up-regulated the expression of both lipolytic and lipogenic genes as determined by real-time RT-PCR. Furthermore, CORT impaired mitochondrial biogenesis and oxidative function in epididymal WAT. The reactive oxygen species production was increased and the activities of anti-oxidative enzymes were reduced by CORT treatment as well. Taken together, these findings reveal that chronic CORT administration-induced epididymal adiposity is, at least in part, associated with mitochondrial dysfunction in mouse epididymal white adipose tissue.

Forced swimming-induced oxytocin release into blood and brain: Effects of adrenalectomy and corticosterone treatment.

PubMed

Torner, Luz; Plotsky, Paul M; Neumann, Inga D; de Jong, Trynke R

2017-03-01

The oxytocin (OXT) system is functionally linked to the HPA axis in a reciprocal and complex manner. Certain stressors are known to cause the simultaneous release of OXT and adrenocorticotrophic hormone (ACTH) followed by corticosterone (CORT). Furthermore, brain OXT attenuates ACTH and CORT responses. Although there are some indications of CORT influencing OXT neurotransmission, specific effects of CORT on neurohypophyseal or intra-hypothalamic release of OXT have not been studied in detail. In the present set of experiments, adult male rats were adrenalectomized (ADX) or sham-operated and fitted with a jugular vein catheter and/or microdialysis probe targeting the hypothalamic paraventricular nucleus (PVN). Blood samples and dialysates were collected before and after forced swimming (FS) and analyzed for CORT, ACTH and AVP concentrations (in plasma) and OXT concentrations (in plasma and dialysates). Experimental treatments included acute infusion of CORT (70 or 175μg/kg i.v.) 5min prior to FS, or subcutaneous placement of 40% CORT pellets resulting in stable CORT levels in the normal basal range. Although ADX did not alter basal OXT concentrations either in plasma or in microdialysates from the PVN, it did cause an exaggerated peripheral secretion of OXT and a blunted intra-PVN release of OXT in response to FS. CORT pellets did not influence either of these ADX-induced effects, while acute infusion of 175μg/kg CORT rescued the stress-induced rise in OXT release within the PVN and modestly increased peripheral OXT secretion. In conclusion, these results indicate that CORT regulates both peripheral and intracerebral OXT release, but in an independent manner. Whereas the peripheral secretion of OXT occurs simultaneously to HPA axis activation in response to FS and is modestly influenced by CORT, HPA axis activation and circulating CORT strongly contribute to the stress-induced stimulation of OXT release within the PVN. Copyright © 2016 Elsevier Ltd. All rights reserved.

Sensitization of restraint-induced corticosterone secretion after chronic restraint in rats: Involvement of 5-HT7 receptors

PubMed Central

García-Iglesias, Brenda B.; Mendoza-Garrido, María E.; Gutiérrez-Ospina, Gabriel; Rangel-Barajas, Claudia; Noyola-Díaz, Martha; Terrón, José A.

2013-01-01

Serotonin (5-HT) modulates the hypothalamic-pituitary-adrenal (HPA) axis response to stress. We examined the effect of chronic restraint stress (CRS; 20 min/day) as compared to control (CTRL) conditions for 14 days, on: 1) restraint-induced ACTH and corticosterone (CORT) secretion in rats pretreated with vehicle or SB-656104 (a 5-HT7 receptor antagonist); 2) 5-HT7 receptor-like immunoreactivity (5-HT7-LI) and protein in the hypothalamic paraventricular nucleus (PVN) and adrenal glands (AG); 3) baseline levels of 5-HT and 5-hydroxyindolacetic acid (5-HIAA), and 5-HIAA/5-HT ratio in PVN and AG; and 4) 5-HT-like immunoreactivity (5-HT-LI) in AG and tryptophan hydroxylase (TPH) protein in PVN and AG. On day 15, animals were subdivided into Treatment and No treatment groups. Treatment animals received an i.p. injection of vehicle or SB-656104; No Treatment animals received no injection. Sixty min later, Treatment animals were either decapitated with no further stress (0 min) or submitted to acute restraint (10, 30, 60 or 120 min); hormone serum levels were measured. No Treatment animals were employed for the rest of measurements. CRS decreased body weight gain and increased adrenal weight. In CTRL animals, acute restraint increased ACTH and CORT secretion in a time of restraint-dependent manner; both responses were inhibited by SB-656104. Exposure to CRS abolished ACTH but magnified CORT responses to restraint as compared to CTRL conditions; SB-656104 had no effect on ACTH levels but significantly inhibited sensitized CORT responses. In CTRL animals, 5-HT7-LI was detected in magnocellular and parvocellular subdivisions of PVN and sparsely in adrenal cortex. Exposure to CRS decreased 5-HT7-LI and protein in the PVN, but increased 5-HT7-LI in the adrenal cortex and protein in whole AG. Higher 5-HT and 5-HIAA levels were detected in PVN and AG from CRS animals but 5-HIAA/5-HT ratio increased in AG only. Finally, whereas 5-HT-LI was sparsely observed in the adrenal cortex of CTRL animals, it strongly increased in the adrenal cortex of CRS animals. No TPH protein was detected in AG from both animal groups. Results suggest that CRS promotes endocrine disruption involving decreased ACTH and sensitized CORT responses to acute restraint. This phenomenon may be associated with increased function and expression of 5-HT7 receptors as well as 5-HT turnover in AG. PMID:23542440

Extraction and analysis of cortisol from human and monkey hair.

PubMed

Meyer, Jerrold; Novak, Melinda; Hamel, Amanda; Rosenberg, Kendra

2014-01-24

The stress hormone cortisol (CORT) is slowly incorporated into the growing hair shaft of humans, nonhuman primates, and other mammals. We developed and validated a method for CORT extraction and analysis from rhesus monkey hair and subsequently adapted this method for use with human scalp hair. In contrast to CORT "point samples" obtained from plasma or saliva, hair CORT provides an integrated measure of hypothalamic-pituitary-adrenocortical (HPA) system activity, and thus physiological stress, during the period of hormone incorporation. Because human scalp hair grows at an average rate of 1 cm/month, CORT levels obtained from hair segments several cm in length can potentially serve as a biomarker of stress experienced over a number of months. In our method, each hair sample is first washed twice in isopropanol to remove any CORT from the outside of the hair shaft that has been deposited from sweat or sebum. After drying, the sample is ground to a fine powder to break up the hair's protein matrix and increase the surface area for extraction. CORT from the interior of the hair shaft is extracted into methanol, the methanol is evaporated, and the extract is reconstituted in assay buffer. Extracted CORT, along with standards and quality controls, is then analyzed by means of a sensitive and specific commercially available enzyme immunoassay (EIA) kit. Readout from the EIA is converted to pg CORT per mg powdered hair weight. This method has been used in our laboratory to analyze hair CORT in humans, several species of macaque monkeys, marmosets, dogs, and polar bears. Many studies both from our lab and from other research groups have demonstrated the broad applicability of hair CORT for assessing chronic stress exposure in natural as well as laboratory settings.

Methodological considerations for measuring glucocorticoid metabolites in feathers

PubMed Central

Berk, Sara A.; McGettrick, Julie R.; Hansen, Warren K.; Breuner, Creagh W.

2016-01-01

In recent years, researchers have begun to use corticosteroid metabolites in feathers (fCORT) as a metric of stress physiology in birds. However, there remain substantial questions about how to measure fCORT most accurately. Notably, small samples contain artificially high amounts of fCORT per millimetre of feather (the small sample artefact). Furthermore, it appears that fCORT is correlated with circulating plasma corticosterone only when levels are artificially elevated by the use of corticosterone implants. Here, we used several approaches to address current methodological issues with the measurement of fCORT. First, we verified that the small sample artefact exists across species and feather types. Second, we attempted to correct for this effect by increasing the amount of methanol relative to the amount of feather during extraction. We consistently detected more fCORT per millimetre or per milligram of feather in small samples than in large samples even when we adjusted methanol:feather concentrations. We also used high-performance liquid chromatography to identify hormone metabolites present in feathers and measured the reactivity of these metabolites against the most commonly used antibody for measuring fCORT. We verified that our antibody is mainly identifying corticosterone (CORT) in feathers, but other metabolites have significant cross-reactivity. Lastly, we measured faecal glucocorticoid metabolites in house sparrows and correlated these measurements with corticosteroid metabolites deposited in concurrently grown feathers; we found no correlation between faecal glucocorticoid metabolites and fCORT. We suggest that researchers should be cautious in their interpretation of fCORT in wild birds and should seek alternative validation methods to examine species-specific relationships between environmental challenges and fCORT. PMID:27335650

Stress hormones in relation to breeding status and territory location in colonial king penguin: a role for social density?

PubMed

Viblanc, Vincent A; Gineste, Benoit; Stier, Antoine; Robin, Jean-Patrice; Groscolas, René

2014-07-01

Because glucocorticoid (stress) hormones fundamentally affect various aspects of the behaviour, life history and fitness of free-living vertebrates, there is a need to understand the environmental factors shaping their variation in natural populations. Here, we examined whether spatial heterogeneity in breeding territory quality affected the stress of colonial king penguin (Aptenodytes patagonicus). We assessed the effects of local climate (wind, sun and ambient temperature) and social conditions (number of neighbours, distance to neighbours) on the baseline levels of plasma total corticosterone (CORT) in 77 incubating and 42 chick-brooding birds, breeding on territories of central or peripheral colony location. We also assessed the oxidative stress status of a sub-sample of central vs. peripheral chick-brooders to determine whether chronic stress arose from breeding on specific territories. On average, we found that brooders had 55% higher CORT levels than incubators. Regardless of breeding status, central birds experienced greater social density (higher number of neighbours, shorter distance between territories) and had higher CORT levels than peripheral birds. Increasing social density positively explained 40% of the variation in CORT levels of both incubators and brooders, but the effect was more pronounced in brooders. In contrast, climate was similar among breeding territories and did not significantly affect the CORT levels of breeding birds. In brooders, oxidative stress status was not affected by local density or weather conditions. These results highlight that local heterogeneity in breeding (including social) conditions may strongly affect the stress levels of breeding seabirds. The fitness consequences of such variation remain to be investigated.

Reproduction in female copperhead snakes (Agkistrodon contortrix): plasma steroid profiles during gestation and post-birth periods.

PubMed

Smith, Charles F; Schuett, Gordon W; Hoss, Shannon K

2012-04-01

We investigated levels of plasma progesterone (P4), 17β-estradiol (E2), testosterone (T), and corticosterone (CORT) during gestation and post-birth periods in wild-collected female copperhead snakes (Viperidae; Agkistrodon contortrix). We also sought to determine whether CORT levels at (or near) birth dramatically increase and were correlated with duration of labor and litter size. Specifically, pregnant subjects (N = 14) were collected during early- to mid-gestation, held in the laboratory, and repeatedly bled to obtain plasma for steroid analyses. Progesterone showed significant changes during gestation, with the highest levels at the onset of sampling (circa 50 days prior to birth); P4 progressively declined up to parturition, and basal levels were observed thereafter. At the onset of sampling, E2 was at peak levels and fell sharply at circa 30 days prior to birth, a trend observed throughout the post-birth sampling period. Throughout the entire sampling period, T was undetectable. Although CORT showed no significant changes during gestation and several days following parturition, there was a highly significant peak at the time of birth. Our findings mirror the results of previous studies on pregnancy and steroid hormones of other live-bearing snakes, lizards, and mammals. As expected, there was a significant relationship between duration of labor and litter size; however, although levels of CORT did not achieve significance, there was a positive trend with litter size. We suggest that elevation of CORT at birth is involved in the mobilization and regulation of energy stores necessary for the physiological process of parturition and as a possible mechanism to trigger birth.

Physiological indices of stress in wild and captive garter snakes: correlations, repeatability, and ecological variation.

PubMed

Sparkman, Amanda M; Bronikowski, Anne M; Williams, Shelby; Parsai, Shikha; Manhart, Whitney; Palacios, Maria G

2014-08-01

Glucocorticoids and leukocyte ratios have become the most widespread variables employed to test hypotheses regarding physiological stress in wild and captive vertebrates. Little is known, however, regarding how these two indices of stress covary in response to stressors, their repeatability within individuals, and differences in response time upon capture. Furthermore, few studies compare stress indices between captive and wild populations, to assess potential alteration of stress physiology in captivity. To address these issues, we examined corticosterone (CORT) and heterophil to lymphocyte (H:L) ratios in two ecotypes of the garter snake Thamnophis elegans. We found that CORT and H:L ratios were not correlated within individuals, and both variables showed little or no repeatability over a period of months. CORT levels, but not H:L ratios, were higher for individuals sampled after 10min from the time of capture. However, both variables showed similar patterns of ecotypic variation, and both increased over time in gravid females maintained in captivity for four months. We suggest that CORT and H:L ratios are both useful, but disparate indices of stress in this species, and may show complex relationships to each other and to ecological and anthropogenic variables. Copyright © 2014 Elsevier Inc. All rights reserved.

Effects of banding or burdizzo castration of bulls on neutrophil phagocytosis and respiratory burst, CD62-L expression, and serum interleukin-8 concentration.

PubMed

Pang, W Y; Earley, B; Sweeney, T; Pirani, S; Gath, V; Crowe, M A

2009-10-01

The objective was to investigate measures of neutrophil function in response to banding or burdizzo castration of bulls. Thirty-two Holstein-Friesian bulls (14 mo old, 505 +/- 7.8 kg of BW) were assigned to 1 of 4 treatment groups: 1) sham-handled control (CON); 2) banding castration alone (BAND); 3) burdizzo castration alone (BURD); or 4) cortisol infusion (CORT) as a further control group. For each group on d -14, 8 animals (2 animals/treatment) were tied up in tie stalls (day of treatment = d 0). At -2, 2, 6, 12, 24, 48, 72, and 144 h relative to treatment time, blood samples were collected for analyses of neutrophil phagocytosis and respiratory burst, neutrophil CD62-L expression, and serum IL-8 concentration. Leukocyte counts, phagocytosis activity, and CD62-L expression were similar (P > 0.05) among the 4 treatment groups. The BURD castrates had greater burst activity compared with BAND castrates (P = 0.048) and CON (P = 0.01) at 72 h posttreatment. The BURD castrates had a greater percentage of granulocyte positive leukocytes (Gr%; P < 0.01) at 2 h posttreatment compared with CON and CORT bulls. The BURD castrates had greater (P < 0.05) Gr% compared with BAND, CON, and CORT animals at 24, 48, and 72 h posttreatment. The BURD and BAND castrates had greater Gr% (P < 0.05) compared with CORT bulls at 144 h posttreatment. In general, BAND, BURD, and CORT did not affect serum IL-8 concentration. Banding castration, BURD, and CORT did not induce leukocytosis, whereas BURD induced a modest neutrophilia. Neutrophil functioning in terms of phagocytosis and respiratory burst and serum IL-8 concentration were not compromised by BAND, BURD, and CORT. These findings indicate nonsurgical castration is unlikely to induce a severe acute systemic inflammatory response in terms of neutrophil function.

Elevated corticosterone in the dorsal hindbrain increases plasma norepinephrine and neuropeptide Y, and recruits a vasopressin response to stress

PubMed Central

Daubert, Daisy L.; Looney, Benjamin M.; Clifton, Rebekah R.; Cho, Jake N.

2014-01-01

Repeated stress and chronically elevated glucocorticoids cause exaggerated cardiovascular responses to novel stress, elevations in baseline blood pressure, and increased risk for cardiovascular disease. We hypothesized that elevated corticosterone (Cort) within the dorsal hindbrain (DHB) would: 1) enhance arterial pressure and neuroendocrine responses to novel and repeated restraint stress, 2) increase c-Fos expression in regions of the brain involved in sympathetic stimulation during stress, and 3) recruit a vasopressin-mediated blood pressure response to acute stress. Small pellets made of 10% Cort were implanted on the surface of the DHB in male Sprague-Dawley rats. Blood pressure was measured by radiotelemetry. Cort concentration was increased in the DHB in Cort-treated compared with Sham-treated rats (60 ± 15 vs. 14 ± 2 ng Cort/g of tissue, P < 0.05). DHB Cort significantly increased the integrated arterial pressure response to 60 min of restraint stress on days 6, 13, and 14 following pellet implantation (e.g., 731 ± 170 vs. 1,204 ± 68 mmHg/60 min in Sham- vs. Cort-treated rats, day 6, P < 0.05). Cort also increased baseline blood pressure by day 15 (99 ± 2 vs. 108 ± 3 mmHg for Sham- vs. Cort-treated rats, P < 0.05) and elevated baseline plasma norepinephrine and neuropeptide Y concentrations. Cort significantly enhanced stress-induced c-Fos expression in vasopressin-expressing neurons in the paraventricular nucleus of the hypothalamus, and blockade of peripheral vasopressin V1 receptors attenuated the effect of DHB Cort to enhance the blood pressure response to restraint. These data indicate that glucocorticoids act within the DHB to produce some of the adverse cardiovascular consequences of chronic stress, in part, by a peripheral vasopressin-dependent mechanism. PMID:24829502

Glucocorticoid effects on sheep peripheral blood mononuclear cell proliferation and cytokine production under in vitro hyperthermia.

PubMed

Caroprese, M; Ciliberti, M G; De Palo, P; Santillo, A; Sevi, A; Albenzio, M

2018-06-27

The present experiment aimed at understanding the effects of cortisol levels on sheep peripheral blood mononuclear cell (PBMC) proliferation and cytokine production during hyperthermia. To mimic stress related to the exposition of high ambient temperatures, PBMC were cultured at 43°C for 12 h, and subsequently at 39°C for additional 12 h. Cells in normothermia were cultured at 39°C for 24 h. Phytohemagglutinin-stimulated PBMC were cultured with different cortisol levels: 0 ng/mL; 100 ng/mL, representing the physiological cortisol concentration simulating stress condition (Cort100); and 1,000 ng/mL, representing the hyperactivated hypothalamic-pituitary-adrenal axis (Cort1000). Phytohemagglutinin-stimulated PBMC with 0 ng/mL of cortisol concentration represented the positive control, whereas nonstimulated PBMC without cortisol represented the negative control (NC). The free cell supernatants were collected for the determination of IL-6, IL-1β, and IL-10 by ELISA. Bromodeoxyuridine assay was performed on cells to determine cell proliferation. Exposition to hyperthermia negatively affected cell proliferation, IL-6, IL-1β, and IL-10 concentrations in cell supernatants. The interaction of hyperthermia and cortisol level affected both cell proliferation and IL-10 production. Both PBMC proliferation and IL-10 production in positive control, Cort100, and Cort100 decreased at 43°C as compared with 39°C NC. On average, the Cort100 treatment displayed higher concentrations of IL-6 than NC. The present experiment demonstrated that the action of cortisol concentration simulating stress condition on cell proliferation and cytokine production was a permissive/stimulatory action during normothermia, whereas it was a suppressive action during hyperthermia. These data confirmed that cortisol concentration simulating stress condition could have a role in the immune system of sheep via mediating cellular homeostasis in the condition of hyperthermia. The negative effects of hyperthermia on sheep immune responses were apparent when performing an immunological challenge. The Authors. Published by FASS Inc. and Elsevier Inc. on behalf of the American Dairy Science Association®. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

The breeding season duration hypothesis: acute handling stress and total plasma concentrations of corticosterone and androgens in male and female striped plateau lizards (Sceloporus virgatus).

PubMed

Hews, D K; Abell Baniki, A J

2013-10-01

Acute glucocorticoid elevations can be adaptations to short-term stressors. The breeding season hypothesis predicts reduced glucocorticoid responsiveness to acute stressors in populations or species with short breeding seasons. The striped plateau lizard (Sceloporus virgatus) has a short breeding season in Arizona. We measured plasma corticosterone and total androgen levels (dihydrotestosterone and testosterone) following one of the four stress-handling treatments (0, 10, 60, or 180 min). In both sexes, longer handling stress yielded higher corticosterone; females had higher corticosterone than males at all time points. Androgens did not vary with handling duration, in either sex. Combining treatments, plasma androgens correlated positively with corticosterone (CORT) in females but not in males; plasma CORT and body mass residuals were negatively correlated in both sexes, suggesting lizards in poor body condition and/or not investing heavily in reproduction (follicle mass) have higher acute corticosterone. Total plasma androgens and body mass residuals were positively associated in males, but showed no association in females. The maximal CORT elevation after handling stress in this single-clutching species was of comparable magnitude to responses in related multi-clutching lizard species with longer breeding seasons. Using data from studies of multiple populations of three Sceloporus species, we found no relationship between the relative magnitude of the CORT increase and either latitude or elevation, two variables in the literature correlated with duration of the breeding season, and only weak relationships with geographic elevation and actual (not relative) stress-elevated CORT values in this multi-population comparison.

Environmental temperature and stocking density effects on acute phase proteins, heat shock protein 70, circulating corticosterone and performance in broiler chickens

NASA Astrophysics Data System (ADS)

Najafi, Pardis; Zulkifli, Idrus; Amat Jajuli, Nurfarahin; Farjam, Abdoreza Soleimani; Ramiah, Suriya Kumari; Amir, Anna Aryani; O'Reily, Emily; Eckersall, David

2015-11-01

An experiment was conducted to determine the effect of different stocking densities on serum corticosterone (CORT), ovotransferrin (OVT), α1-acid glycoprotein (AGP) and ceruloplasmin (CP) concentrations, brain heat shock protein (HSP) 70 expression and performance in broiler chickens exposed to unheated and heated conditions. Day-old chicks were stocked at 0.100 m2/bird (low density (LD)) or 0.063 m2/bird (high density (HD)), in battery cages and housed in environmentally controlled rooms. From 21 to 35 days of age, birds from each stocking density group were exposed to either 24 or 32 °C. Growth performance was recorded during the heat treatment period, and blood and brain samples were collected to determine CORT, OVT, AGP, CP and HSP 70 levels on day 35. Heat treatment but not stocking density was detrimental to growth performance. There were significant temperature × density interactions for CORT, CP and OVT on day 35. Although HD elevated CORT, CP and OVT when compared to LD, the effects of the former were more obvious under heated condition. Both temperature and density had significant effect on AGP and HSP 70. In conclusion, irrespective of temperature, high stocking density was physiologically stressful to broiler chickens, as indicated by CORT, AGP, CP, OVT and HSP 70, but not detrimental to growth performance and survivability. As it was shown in the present study, AGP, CP and OVT could be useful biomarkers to determine the effect of overcrowding and high temperature on the welfare of broiler chickens.

Stress hormones link food availability and population processes in seabirds

USGS Publications Warehouse

Kitaysky, A.S.; Piatt, John F.; Wingfield, J.C.

2007-01-01

Catastrophic population declines in marine top predators in the northern Pacific have been hypothesized to result from nutritional stress affecting reproduction and survival of individuals. However, empirical evidence for food-related stress in wild animals is frequently lacking or inconclusive. We used a field endocrinology approach to measure stress, identify its causes, and examine a link between stress and population processes in the common murre Uria aalge. We tested the empirical relationship between variations in the stress hormone corticosterone (CORT) and food abundance, reproduction, and persistence of individuals at declining and increasing colonies in Cook Inlet, Alaska, from 1996 to 2001. We found that CORT secretion in murres is independent of colony, reproductive stage effects, and gender of individuals, but is directly negatively correlated with abundance of their food. Baseline CORT reflected current food abundance, whereas acute stress-induced CORT reflected food abundance in the previous month. As food supply diminished, increased CORT secretion predicted a decrease in reproductive performance. At a declining colony, increased baseline levels of CORT during reproduction predicted disappearance of individuals from the population. Persistence of individuals in a growing colony was independent of CORT during reproduction. The obtained results support the hypothesis that nutritional stress during reproduction affects reproduction and survival in seabirds. This study provides the first unequivocal evidence for CORT secretion as a mechanistic link between fluctuations in food abundance and population processes in seabirds. ?? Inter-Research 2007.

Dynamic endocrine responses to stress: evidence for energetic constraints and status dependence in breeding male green turtles.

PubMed

Jessop, Tim S; Knapp, Rosemary; Whittier, Joan M; Limpus, Col J

2002-03-01

During reproduction, male vertebrates may exhibit a continuum of interactions between sex and adrenal steroids during stressful events, the outcome of which may be important in either reducing or promoting male reproductive success. We studied adult male green turtles (Chelonia mydas) to examine if they altered plasma corticosterone (CORT) and androgen levels in response to a standardized capture/restraint stressor as potential mechanisms to maintain reproductive activity during stressful events. At the population level, we found that migrant breeding males had a significantly smaller CORT response to the capture/restraint stressor compared to nonbreeding males and that this decreased response coincided with the generally poorer body condition of migrant breeders. In contrast, plasma androgen levels decreased significantly in response to the capture/restraint stressor in migrant breeding males, but not in nonbreeding and pre-migrant breeding males. For individual migrant breeding males, the magnitude of their CORT and androgen responses to the capture/restraint stressor was highly correlated with their body condition and body length, respectively. Our results demonstrate that male green turtles exhibit complex interactions in their endocrine responses to a capture/restraint stressor and that variation in these interactions is associated with differences in males' reproductive, energetic, and physical state. We hypothesize that interplay between physical status and plasma hormone responses to stressors could have important consequences for male green turtle reproduction.

Increased Hair Cortisol Concentrations and BMI in Patients With Pituitary-Adrenal Disease on Hydrocortisone Replacement.

PubMed

Staufenbiel, Sabine M; Andela, Cornelie D; Manenschijn, Laura; Pereira, Alberto M; van Rossum, Elisabeth F C; Biermasz, Nienke R

2015-06-01

Intrinsic imperfections and lack of reliable biomarkers preclude optimal individual dosing of hydrocortisone replacement in adrenal insufficiency (AI). However, the clinical relevance of optimal dosing is exemplified by frequently occurring side effects of overreplacement and the dangers of underreplacement. Cortisol in scalp hair has been identified as a retrospective biomarker for long-term cortisol exposure. We compared hair cortisol concentrations (CORT(hair)) of patients with primary or secondary AI on replacement therapy with those of patient controls with a pituitary disease without AI (PCs) and of healthy controls (HCs). In this cross-sectional study, hair samples and anthropometric data were collected in 132 AI patients (52 males), 42 PCs (11 males), and 195 HCs (90 males). The proximal 3 cm of hair were used. CORT(hair) were measured using an ELISA. CORT(hair) were higher in AI patients than in HCs and PCs (P < .001), and hydrocortisone dose correlated with CORT(hair) (P = .04). Male AI patients demonstrated higher CORT(hair) than female patients (P < .001). AI patients had higher body mass index (BMI) than HCs (P < .001), and BMI correlated with CORT(hair) in the whole sample (P < .001). Physiological hydrocortisone replacement is associated with increased CORT(hair). The association between CORT(hair) and BMI could suggest a mild overtreatment that may lead to adverse anthropomorphic side effects, especially in males. CORT(hair) measurements may be a promising additional tool to monitor cumulative hydrocortisone replacement in AI.

Corticosterone-responsive and -unresponsive metabolic characteristics of adrenalectomized rats.

PubMed

Hamelink, C R; Currie, P J; Chambers, J W; Castonguay, T W; Coscina, D V

1994-09-01

Glucocorticoids are important in influencing substrate flux through the metabolic pathways. This study was designed to answer the question "Does adrenalectomy (ADX) cause a shift toward fat metabolism as measured by a decrease in respiratory quotient (RQ)?" Male Sprague-Dawley rats were divided into four groups, ADX, ADX + 20% corticosterone (Cort) (ADX-20%), ADX + 40% Cort (ADX-40%), or sham-operated controls (Sham). ADX-20% received 50 mg and ADX-40% 100 mg Cort dissolved in 250-mg cholesterol pellets and placed subcutaneously. Each rat was monitored for 90 min four times both during a preoperative period and again after a 1-wk postsurgical recovery period in an indirect calorimeter. Cort prevented ADX-induced suppression of weight gain and food intake. ADX decreased motoric activity in both the light and dark periods. Cort restored activity to Sham levels. ADX decreased RQ only in the dark (0.858 ADX vs. 0.891 Sham) and was reversed only in the ADX-40% group. Energy expenditure (EE) was depressed in both the light and dark by ADX; Cort partially restored EE to Sham values in the light period.

The association between male-biased sex ratio and indicators of stress in red-spotted newts.

PubMed

Aspbury, Andrea S; Grayson, Kristine L; Fantaye, Selamawit; Nichols, Ian; Myers-Burton, Miranda; Ortiz-Mangual, Xavier; Gabor, Caitlin R

2017-05-01

In populations with a male-biased operational sex ratio, coercive mating by males can have fitness consequences for females. One component of reduced fitness for females in populations with a male-biased OSR may be greater activation of the stress response, resulting in higher corticosterone release rates (CORT; a glucocorticoid stress hormone in amphibians). We test the hypothesis that a male-biased sex ratio affects female activity and release rates of CORT and testosterone (T) in male and female red-spotted newts (Notophthalmus viridescens). First, we evaluated if chemical cues from a male-biased sex ratio affect activity and CORT release rates in females. We predicted that females exposed to chemical cues of three males would be less active and have higher CORT release rates than those exposed to chemical cues of one male. Second, we measured CORT release rates of red-spotted newts in field enclosures with either a male-biased or a female-biased sex ratio. We predicted that females in the male-biased treatment would have higher CORT and T release rates than those in a female-biased treatment, owing to higher levels of male harassment. We also predicted that males would have higher CORT and T release rates in male-biased treatments due to higher levels of male-male competition. Females were not less active in response to chemical cues from more males over fewer males, but there was a positive relationship between female activity and CORT when they were exposed to the cues of three males. We also found that females, but not males, in the male-biased sex ratio treatment had higher CORT and T release rates than those in the female-biased treatment. Our results support the hypothesis that a male-biased sex ratio leads to a higher stress response, which may underlie the observed decrease in immune function and body condition in previous work exposing female red-spotted newts to a male-biased sex ratio. This study furthers our understanding of the mechanistic basis for costs associated with a male-biased sex ratio in a pond-breeding amphibian. Copyright © 2017 Elsevier Inc. All rights reserved.

Signaling stress? An analysis of phaeomelanin-based plumage color and individual corticosterone levels at two temporal scales in North American barn swallows, Hirundo rustica erythrogaster.

PubMed

Jenkins, Brittany R; Vitousek, Maren N; Safran, Rebecca J

2013-09-01

Sexually selected traits confer greater reproductive benefits to individuals with more elaborate forms of the signal. However, whether these signals convey reliable information about the physiology underlying trait development remains unknown in many species. The steroid hormone corticosterone (CORT) mediates important physiological and behavioral processes during the vertebrate stress response, and CORT secretion itself can be modulated by melanocortins. Thus, sexually selected melanin-based plumage coloration could function as an honest signal of an individual's ability to respond to stressors. This hypothesis was tested in North American barn swallows, Hirundo rustica erythrogaster, where males with darker ventral plumage color exhibit higher phaeomelanin content and are more successful at reproduction. Because reproductive behavior occurs months after plumage signals are developed, we also addressed the potential temporal disconnect of physiological state during trait development and trait advertisement by analyzing three different measurements of CORT levels in adult males during the breeding season (trait advertisement) and in nestling males while they were growing their feathers (trait development). Variation in adult plumage color did not predict baseline or stress-induced CORT, or stress responsiveness. Likewise, there was no relationship between nestling plumage color and any of the CORT measurements, but heavier nestlings had significantly lower baseline CORT. Our finding that a predominantly phaeomelanin-based trait is unrelated to circulating CORT suggests that phaeomelanin and eumelanin signals may convey different physiological information, and highlights the need for further study on the biochemical links between the hypothalamic-pituitary-adrenal (HPA) axis and the production of different melanin-based pigments. © 2013.

Chronic corticosterone treatment enhances extinction-induced depression in aged rats.

PubMed

Huston, Joseph P; Komorowski, Mara; de Souza Silva, Maria A; Lamounier-Zepter, Valéria; Nikolaus, Susanne; Mattern, Claudia; Müller, Christian P; Topic, Bianca

2016-11-01

Withdrawal and avoidance behavior are common symptoms of depression and can appear as a consequence of absence of reward, i.e. extinction-induced depression (EID). This is particularly relevant for the aged organism subjected to pronounced loss of former rewards. Avoidance of the former site of reward and increased withdrawal into a distant compartment accompany extinction of food-rewarded behavior in rodent models. During extinction, behavioral markers for re-learning dissociate from indicators of extinction-induced depression. Here we examined the effect of a chronic treatment with corticosterone (CORT), a well-known inducer of depression-related behavior, on EID in adult and aged rats. Adult (3-4months) and aged (18months) male rats were treated with CORT via drinking water for 3weeks prior to extinction of a cued food-reward task. CORT treatment increased the distance from the site of reward and decreased goal tracking behavior during extinction, especially in the aged rats. Plasma hormone levels measured before and after restraint stress showed a decline in basal ACTH- and CORT-levels after chronic CORT treatment in aged animals. The treatment significantly impaired the HPA-axis activation after acute stress in both, adult and aged animals, alike. Altogether, these findings show an enhancement of EID after chronic CORT treatment in the aged organism, which may be mediated by an impaired HPA-axis sensitivity. These findings may have special relevance for the investigation of human geriatric depression. Copyright © 2016 Elsevier Inc. All rights reserved.

Effect of forced exercise and exercise withdrawal on memory, serum and hippocampal corticosterone levels in rats.

PubMed

Radahmadi, Maryam; Alaei, Hojjatallah; Sharifi, Mohammad Reza; Hosseini, Nasrin

2015-10-01

Evidence suggests that there are positive effects of exercise on learning and memory. Moreover, some studies have demonstrated that forced exercise plays the role of a stressor. This study was aimed at investigating the effects of different timing of exercise and exercise withdrawal on memory, and serum and hippocampal corticosterone (CORT) levels. Wistar rats were randomly divided into five groups: control, sham, exercise-rest (exercise withdrawal), rest-exercise (exercised group), and exercise-exercise (continuous exercise). Rats were forced to run on a treadmill for 1 h/day at a speed 20-21-m/min. Memory function was evaluated by the passive avoidance test in different intervals (1, 7 and 21 days) after foot shock. Findings showed that after the exercise withdrawal, short-term and mid-term memories, had significant enhancement compared to the control group, while the long-term memory did not present this result. In addition, the serum and hippocampal CORT levels were at the basal levels after the rest period in the exercise-rest group. In the rest-exercise group, exercise improved mid- and long-term memories, whereas continuous exercise improved all types short-, mid- and long-term memories, particularly the mid-term memory. Twenty-one and forty-two days of exercise significantly decreased the serum and hippocampal CORT levels. It seems that exercise for at least 21 days with no rest could affect biochemical factors in the brain. Also, regular continuous exercise plays an important role in memory function. Hence, the duration and withdraw of exercise are important factors for the neurobiological aspects of the memory responses.

Sediment geochemistry of Corte Madera Marsh, San Francisco Bay, California: have local inputs changed, 1830-2010?

USGS Publications Warehouse

Takesue, Renee K.; Jaffe, Bruce E.

2013-01-01

Large perturbations since the mid-1800s to the supply and source of sediment entering San Francisco Bay have disturbed natural processes for more than 150 years. Only recently have sediment inputs through the Sacramento-San Joaquin Delta (the Delta) decreased to what might be considered pre-disturbance levels. Declining sediment inputs to San Francisco Bay raise concern about continued tidal marsh accretion, particularly if sea level rise accelerates in the future. The aim of this study is to explore whether the relative amount of local-watershed sediment accumulating in a tidal marsh has changed as sediment supply from the Sacramento-San Joaquin Rivers has decreased. To address this question, sediment geochemical indicators, or signatures, in the fine fraction (silt and clay) of Sacramento River, San Joaquin River, San Francisco Bay, and Corte Madera Creek sediment were identified and applied in sediment recovered from Corte Madera Marsh, one of the few remaining natural marshes in San Francisco Bay. Total major, minor, trace, and rare earth element (REE) contents of fine sediment were determined by inductively coupled plasma mass and atomic emission spectroscopy. Fine sediment from potential source areas had the following geochemical signatures: Sacramento River sediment downstream of the confluence of the American River was characterized by enrichments in chromium, zirconium, and heavy REE; San Joaquin River sediment at Vernalis and Lathrop was characterized by enrichments in thorium and total REE content; Corte Madera Creek sediment had elevated nickel contents; and the composition of San Francisco Bay mud proximal to Corte Madera Marsh was intermediate between these sources. Most sediment geochemical signatures were relatively invariant for more than 150 years, suggesting that the composition of fine sediment in Corte Madera Marsh is not very sensitive to changes in the magnitude, timing, or source of sediment entering San Francisco Bay through the Delta. Nor does there appear to be a ubiquitous increase in the proportion of fine sediment from Corte Madera watershed accumulating in the marsh during the last 20 years when sediment inflows through the Delta have decreased to pre-disturbance levels. We conclude that a large, well-mixed reservoir, such as the transportable fine sediment pool in San Francisco Bay, is the primary source of sediment to Corte Madera Marsh, and this source buffers the marsh against changes in sediment supply from the Delta and local watersheds. This study also found that Corte Madera Marsh sediment between about 10-30 centimeters depth is highly contaminated with lead, likely a legacy of lead smelter operations near Carquinez Strait and leaded gasoline use.

Corticosterone affects the differentiation of a neuronal cerebral cortex-derived cell line through modulation of the nicotinic acetylcholine receptor.

PubMed

Baier, C J; Franco, D L; Gallegos, C E; Mongiat, L A; Dionisio, L; Bouzat, C; Caviedes, P; Barrantes, F J

2014-08-22

Chronic exposure to stress hormones has an impact on brain structures relevant to cognition. Nicotinic acetylcholine receptors (AChRs) are involved in numerous cognitive processes including learning and memory formation. In order to better understand the molecular mechanisms of chronic stress-triggered mental disease, the effect of corticosterone (CORT) on the biology of AChRs was studied in the neuronal cell line CNh. We found that chronic treatment with CORT reduced the expression levels of the α7-type neuronal AChR and, to a lesser extent, of α4-AChR. CORT also delayed the acquisition of the mature cell phenotype in CNh cells. Chronic nicotine treatment affected the differentiation of CNh cells and exerted a synergistic effect with CORT, suggesting that AChR could participate in signaling pathways that control the cell cycle. Overexpression of α7-AChR-GFP abolished the CORT effects on the cell cycle and the specific α7-AChR inhibitor, methyllycaconitine, mimicked the proliferative action exerted by CORT. Whole-cell voltage-clamp recordings showed a significant decrease in nicotine-evoked currents in CORT-treated cells. Taken together, these observations indicate that AChRs, and the α7-AChR in particular, could act as modulators of the differentiation of CNh cells and that CORT could impair the acquisition of a mature phenotype by affecting the function of this AChR subtype. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

A Preliminary Study of the Effects of Repeated Massage on Hypothalamic–Pituitary–Adrenal and Immune Function in Healthy Individuals: A Study of Mechanisms of Action and Dosage

PubMed Central

Schettler, Pamela; Bresee, Catherine

2012-01-01

Abstract Objectives This study gathers preliminary data about the biologic effects of repeated Swedish massage therapy compared to a light-touch control condition. Design The study design was a 5-week comparison of repeated Swedish massage and light touch on oxytocin (OT), arginine-vasopressin (AVP), adrenal corticotropin hormone (ACTH), cortisol (CORT), circulating phenotypic lymphocyte markers, and mitogen-stimulated cytokine function. Setting The setting was an outpatient research unit in an academic medical center. Participants The study subjects were medically and psychiatrically healthy young adults. Intervention The study comprised 45 minutes of Swedish massage or light touch, using highly specified and identical protocols, either weekly or twice weekly for 5 weeks. Outcome measures The outcome measures were mean differences between massage and light touch on OT, AVP, ACTH, CORT, lymphocyte markers, and cytokine levels. Results Compared to the touch control condition, weekly Swedish massage stimulated a sustained pattern of increased circulating phenotypic lymphocyte markers and decreased mitogen-stimulated cytokine production, similar to what was previously reported for a single massage session, while having minimal effect on hypothalamic–pituitary–adrenal function. Twice-weekly massage produced a different response pattern with increased OT levels, decreased AVP, and decreased CORT but little effect on circulating lymphocyte phenotypic markers and a slight increase in mitogen-stimulated interferon-γ, tumor necrosis factor-α, interleukin (IL)-1b and IL-2 levels, suggesting increased production of pro-inflammatory cytokines. Conclusions There are sustained cumulative biologic actions for the massage and touch interventions that persist for several days or a week, and these differ profoundly depending on the dosage (frequency) of sessions. Confirmatory studies in larger samples are needed. PMID:22775448

Chronic Stress Enhances the Corticosterone Response and Neurotoxicity to +3,4-Methylenedioxymethamphetamine (MDMA): The Role of Ambient Temperature

PubMed Central

Johnson, Bethann N.

2010-01-01

Stress facilitates drug abuse by humans. In rodents, stress enhances the neurochemical, neuroendocrine, and behavioral responses to psychostimulants. Although chronic unpredictable stress (CUS) enhances the acute hyperthermic and long-term monoamine-depleting effects of the psychostimulant +3,4-methylenedioxymethamphetamine (MDMA), the roles of hyperthermia and corticosterone (CORT) in mediating the stress-induced enhancement of MDMA-induced serotonin (5-HT) and dopamine (DA) depletions are unknown. Rats were exposed to 10 days of CUS and then challenged with MDMA (5 mg/kg i.p. once every 2 h for a total of four injections). Prior exposure to CUS augmented MDMA-induced hyperthermia and plasma CORT secretion and the long-term depletions in 5-HT content in striatum, hippocampus, and frontal cortex and DA content in striatum. A reduced ambient temperature of 21°C attenuated the hyperthermia, CORT secretion, and 5-HT decreases after MDMA in nonstressed rats. The lower ambient temperature also prevented the augmented hyperthermia, CORT secretion, and enhanced 5-HT and DA depletions after MDMA in chronically stressed rats to levels exhibited by nonstressed, MDMA-treated rats. To investigate the role of CORT on monoamine depletions in response to MDMA, stressed and nonstressed rats were treated with the CORT synthesis inhibitor metyrapone during exposure to MDMA. Metyrapone prevented CORT secretion in both stressed and nonstressed rats but did not modify 5-HT or DA depletions in any brain region examined. This study suggests that enhanced CORT is a consequence of enhanced hyperthermia and the CUS-induced enhancements of MDMA-induced monoamine depletions may be mediated by hyperthermia but not CORT. PMID:20634423

Neonatal Handling Increases Cardiovascular Reactivity to Contextual Fear Conditioning in Borderline Hypertensive Rats (BHR)

PubMed Central

Sanders, Brian J.; Knoepfler, Jonathan

2008-01-01

Much research has demonstrated that events occurring in early life can have a profound influence on future biobehavioral responses to stressful and emotion provoking situations. The purpose of these studies was to determine the effects of an early environmental manipulation, handling (HAN) on cardiovascular (CV) reactivity, freezing behavior and corticosterone (CORT) responses to contextual fear conditioning in the borderline hypertensive rat (BHR), which is susceptible to environmental stressors. HAN subjects were separated from the nest for 15 min/day on post-natal days 1–14, while non-handled (NON-HAN) controls remained in the home cage. Adult subjects were exposed to the contextual fear conditioning procedure and returned to the chamber 24 h later for a 10 min test period. HAN subjects displayed significantly more freezing behavior compared to NON-HAN(92%±2.2 vs 80.7%±5.7, p < .05). Although resting MAP did not differ between groups, HAN subjects had increased MAP reactivity when re-exposed to the chamber. In addition, HAN subjects had significantly lower CORT levels at the end of the 10 min test period (174.2±9 ng/ml vs 237.2±12.9 ng/ml, p < .05). In the second experiment, CORT responses to 60 min of restraint stress and recovery following return to the home cage were assessed in separate groups of HAN and NON-HAN subjects. HAN subjects showed reduced CORT levels in response to acute restraint stress. These results indicate that neonatal handling can modulate biobehavioral responses to contextual fear conditioning in BHR and may suggest a useful model with which to study emotionality and susceptibility to CV disease. PMID:18538802

A comparison of the short- and long-term effects of corticosterone exposure on extinction in adolescence versus adulthood.

PubMed

Den, Miriam Liora; Altmann, Sarah R; Richardson, Rick

2014-12-01

Human and nonhuman adolescents have impaired retention of extinction of learned fear, relative to juveniles and adults. It is unknown whether exposure to stress affects extinction differently in adolescents versus adults. These experiments compared the short- and long-term effects of exposure to the stress-related hormone corticosterone (CORT) on the extinction of learned fear in adolescent and adult rats. Across all experiments, adolescent and adult rats were trained to exhibit good extinction retention by giving extinction training across 2 consecutive days. Despite this extra training, adolescents exposed to 1 week of CORT (200 μg/ml) in their drinking water showed impaired extinction retention when trained shortly after the CORT was removed (Experiment 1a). In contrast, adult rats exposed to CORT (200 μg/ml) for the same duration did not exhibit deficits in extinction retention (Experiment 1b). Exposing adolescents to half the amount of CORT (100 μg/ml; Experiment 1c) for 1 week similarly disrupted extinction retention. Extinction impairments in adult rats were only observed after 3 weeks, rather than 1 week, of CORT (200 μg/ml; Experiment 1d). Remarkably, however, adult rats showed impaired extinction retention if they had been exposed to 1 week of CORT (200 μg/ml) during adolescence (Experiment 2). Finally, exposure to 3 weeks of CORT (200 μg/ml) in adulthood led to long-lasting extinction deficits after a 6-week drug-free period (Experiment 3). These findings suggest that although CORT disrupts both short- and long-term extinction retention in adolescents and adults, adolescents may be more vulnerable to these effects because of the maturation of stress-sensitive brain regions. (PsycINFO Database Record (c) 2014 APA, all rights reserved).

Association of 24 h maternal deprivation with a saline injection in the neonatal period alters adult stress response and brain monoamines in a sex-dependent fashion.

PubMed

Cabbia, Rafael; Consoli, Amanda; Suchecki, Deborah

2018-04-01

Maternal deprivation (MD) disinhibits the adrenal glands, rendering them responsive to various stressors, including saline injection, and this increased corticosterone (CORT) response can last for as long as 2 h. In the present study, we tested the hypothesis that association of MD on day 11 with a saline injection would alter emotional behavior, CORT response, and brain monoamine levels, in male and female adult rats. Rats were submitted to the novelty suppressed feeding (NSF), the sucrose negative contrast test (SNCT), social investigation test (SIT), and the elevated plus maze (EPM). One quarter of each group was not tested (providing basal values of CORT and brain monoamines) and the remainder was decapitated 15, 45, or 75 min after the EPM, to assess CORT reactivity. Monoamine levels were determined in the hypothalamus (HPT), frontal cortex (FC), amygdala (AMY), ventral, and dorsal hippocampus (vHPC, dHPC, respectively). MD reduced food intake, in the home-cage, and latency to eat in the NSF in both sexes; females explored less the target animal in the SIT and explored more the open arms of the EPM than males; the CORT response to the EPM was greater in maternally-deprived males and females than in their control counterparts, and this response was further elevated in maternally-deprived females injected with saline. Regarding monoamine levels, females were less affected, showing isolated effects of the stressors, while in males, MD increased 5-HT levels in the HPT and decreased this monoamine in the FC, MD associated with saline reduced dopamine levels in all brain regions, except the HPT. MD at 11 days did not alter emotional behaviors in adult rats, but had an impact in neurobiological parameters associated with this class of behaviors. The impact of MD associated with saline on dopamine levels suggests that males may be vulnerable to motivation-related disorders.

Chronic corticosterone exposure reduces hippocampal glycogen level and induces depression-like behavior in mice.

PubMed

Zhang, Hui-yu; Zhao, Yu-nan; Wang, Zhong-li; Huang, Yu-fang

2015-01-01

Long-term exposure to stress or high glucocorticoid levels leads to depression-like behavior in rodents; however, the cause remains unknown. Increasing evidence shows that astrocytes, the most abundant cells in the central nervous system (CNS), are important to the nervous system. Astrocytes nourish and protect the neurons, and serve as glycogen repositories for the brain. The metabolic process of glycogen, which is closely linked to neuronal activity, can supply sufficient energy substrates for neurons. The research team probed into the effects of chronic corticosterone (CORT) exposure on the glycogen level of astrocytes in the hippocampal tissues of male C57BL/6N mice in this study. The results showed that chronic CORT injection reduced hippocampal neurofilament light protein (NF-L) and synaptophysin (SYP) levels, induced depression-like behavior in male mice, reduced hippocampal glycogen level and glycogen synthase activity, and increased glycogen phosphorylase activity. The results suggested that the reduction of the hippocampal glycogen level may be the mechanism by which chronic CORT treatment damages hippocampal neurons and induces depression-like behavior in male mice.

Chronic repeated exposure to weather-related stimuli elicits few symptoms of chronic stress in captive molting and non-molting European starlings (Sturnus vulgaris).

PubMed

de Bruijn, Robert; Reed, J Michael; Romero, L Michael

2017-10-01

Repeated exposure to acute stressors causes dramatic changes in an animal's stress physiology and the cumulative effects are often called chronic stress. Recently we showed that short-term exposure to weather-related stimuli, such as temperature change, artificial precipitation, and food restriction, cause acute responses in captive European starlings (Sturnus vulgaris). Here, we examined the effect of repeated exposure to weather-related stressors on heart rate and corticosterone (CORT) of captive non-molting and molting European starlings. Four times every day for 3 weeks, birds were exposed to either 30 min of a subtle (3°C) decrease in temperature, a short bout of simulated rain, or 2 hr of food removal. The order and time of presentation were randomly assigned on each day. We found no differences in heart rate or heart rate variability. Furthermore, there were no changes in baseline CORT levels, CORT negative feedback efficacy, or maximal adrenal capacity. Mass increased across the experimental period only in molting birds. CORT responses to restraint were decreased in both groups following treatment, suggesting the birds had downregulated their responses to acute stress. Molting birds showed evidence of suppression of the HPA axis compared with non-molting birds, which is consistent with previous research. Overall, our data show that repeated exposure to weather-related stressors does not elicit most of the symptoms normally associated with chronic stress. © 2018 Wiley Periodicals, Inc.

Cortisol and Alpha-amylase changes during an Ultra-Running Event.

PubMed

Deneen, Whitney P; Jones, Alexis B

2017-01-01

Elevated stress hormone concentrations can positively affect an athlete's overall performance during a competition, and in many cases, are necessary to be able to perform exercise. During extreme exercise, the body's ability to utilize energy efficiently can affect an athlete's performance. Elevated hormonal concentrations can have many benefits in regards to an athlete's overall performance during a competition. The purpose of this study was to examine the effects of long distance running, such as seen during an ultra-running event (distances beyond 26.2 miles), on the activity of the hypothalamic-pituitary-adrenocortical (HPA) axis production of cortisol (CORT) as compared to autonomic nervous system production of salivary alpha-amylase (AA). Despite the well-known effects of exercise on CORT and AA response, it is unclear what effect running beyond the marathon distance has on these levels. This study investigates what effect long duration cardio exercise, such as running up to 100K (kilometers) distance, has on the neuroendocrine system, by means of saliva samples provided by participants signed up for an ultra-marathon event. The findings of this study show that the autonomic nervous system may present a response signal during physical stress that is independent of the HPA axis response. At distances beyond the marathon length, the production of CORT and AA was found to be suppressed for athletes, which could help them in their continued performance. Furthermore, this study recognizes a difference in the overall male and female response to stress in regards to CORT and AA production.

Chronic orthostatic and antiorthostatic restraint induce neuroendocrine, immune and neurophysiological disorders in rats

NASA Astrophysics Data System (ADS)

Assenmacher, I.; Mekaouche, M.; Maurel, D.; Barbanel, G.; Givalois, L.; Boissin, J.; Malaval, F.; Ixart, G.

The tail-cast suspension rat model has been developed in ground laboratories interested in space physiology for extensive study of mechanisms causing the pathophysiological syndrome associated with space flights. We used individually-caged male rats to explore the effects of acute and chronic (7d) orthostatic restraint (OR) and head-down anti-orthostatic restraint (AOR) on a series of physiological variables. The acute restraint study showed that (1) the installation of the OR device induced an acute reaction for 2 days, with a substantial rise in ACTH (x2) and CORT (x6), and that (2) the head-down tilt from OR to AOR induced (i) within 10 min and lasting 60 min a 2-fold rise in the intra-cerebro-ventricular pressure (Picv) monitored with an icv telemetric recording system, which receded to normal between 60 and 120 min; and (ii) within 30 min a short-lived 4-fold rise in plasma ACTH and CORT levels. Chronic OR induced (1) the suppression of the diurnal ACTH/CORT rhythm, with increased mean levels, especially for ACTH, (2) a degraded circadian locomotor activity rhythm manifested by a significant reduction in the spectral power of the 24h periodicity and a concomitant emergence of shorter (ultradian) periodicities, (3) an associated, but less pronounced alteration of the diurnal rhythm in body temperature; and (4) a marked increase in baseline plasma levels of IL-1β and an increased reactivity in cytokine release following an E. coli endotoxin (LPS) challenge. AOR induced (1) a similar obliteration of the circadian ACTH/CORT rhythm, (2) the loss of close correlation between ACTH and CORT, (3) a generalized increase in baseline plasma IL-1β levels and (4) more extensive degradation of the arcadian periodicity for both locomotor activity and, to a lesser extent, body temperature, replaced by dominant spectral powers for ultradian periodicities (3 to 10h). In conclusion, both experimental paradigms — but AOR more than OR — caused a blockade of the arcadian rhythmicity of major physiological variables, the loss of normal correlations between ACTH and CORT, and inflammatory-immune hyperreactivity. These pathophysiological disorders may all be parts of a complex chronic stress syndrome.

Corticosterone mediates stress-related increased intestinal permeability in a region-specific manner

PubMed Central

Zheng, Gen; Wu, Shu-Pei; Hu, Yongjun; Smith, David E; Wiley, John W.; Hong, Shuangsong

2012-01-01

Background Chronic psychological stress (CPS) is associated with increased intestinal epithelial permeability and visceral hyperalgesia. It is unknown whether corticosterone (CORT) plays a role in mediating alterations of epithelial permeability in response to CPS. Methods Male rats were subjected to 1-hour water avoidance (WA) stress or subcutaneous CORT injection daily for 10 consecutive days in the presence or absence of corticoid-receptor antagonist RU-486. The visceromotor response (VMR) to colorectal distension (CRD) was measured. The in situ single-pass intestinal perfusion was used to measure intestinal permeability in jejunum and colon simultaneously. Key Results We observed significant decreases in the levels of glucocorticoid receptor (GR) and tight junction proteins in the colon but not the jejunum in stressed rats. These changes were largely reproduced by serial CORT injections in control rats and were significantly reversed by RU-486. Stressed and CORT-injected rats demonstrated a 3-fold increase in permeability for PEG-400 (MW) in colon but not jejunum and significant increase in VMR to CRD, which was significantly reversed by RU-486. In addition, no differences in permeability to PEG-4,000 and PEG-35,000 were detected between control and WA groups. Conclusions & Inferences Our findings indicate that CPS was associated with region-specific decrease in epithelial tight junction protein levels in the colon, increased colon epithelial permeability to low-molecular weight macromolecules which were largely reproduced by CORT treatment in control rats and prevented by RU-486. These observations implicate a novel, region-specific role for CORT as a mediator of CPS-induced increased permeability to macromolecules across the colon epithelium. PMID:23336591

The antidepressant fluoxetine normalizes the nuclear glucocorticoid receptor evoked by psychosocial stress

NASA Astrophysics Data System (ADS)

Mitić, M.; Simić, I.; Djordjević, J.; Radojčić, M. B.; Adžić, M.

2011-12-01

Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis has been implicated in the pathophysiology of depression and stress disorders. Glucocorticoids, key regulators of the stress response, exert diverse effects on cellular processes in the hippocampus. Beside non-genomic pathways, glucocorticoid effects are mediated through activation of the glucocorticoid receptor (GR), a ligand activated transcriptional factor that belongs to the nuclear hormone receptor superfamily. We analysed the GR protein levels both in the cytoplasmic and nuclear compartments of the hippocampus of Wistar rats exposed to chronic psychosocial isolation stress upon chronic fluoxetine (FLU) treatment. Under chronic stress, corticosterone levels (CORT) were decreased compared to the control, and treatment with FLU did not change its level in the stressed rats. At the molecular level, FLU normalized the level of nuclear GR protein in the hippocampus of the stressed rats. Discrepancy between normalization of nuclear GR in the hippocampus and lack of normalization of HPA axis activity judged by CORT, suggests that other brain structures such as the amygdale and prefrontal cortex that also regulate HPA axis activity, seem not to be normalized by the FLU treatment used in our study.

Synergized resmethrin and corticosterone alter the chicken's response to west nile virus

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jankowski, Mark David; Franson, J Christian; Mostl, Erich

2009-01-01

Debate concerning arbovirus control strategies remains contentious because concern regarding the relative risk of viral infection and environmental toxicant exposure is high but inadequately characterized. Taking this into account, mosquito control agencies employ aerial insecticides only after arbovirus surveillance data indicate high local mosquito-infection-rates. Successfully mitigating the risk of adult-mosquito-control insecticides ('adulticides') to non-target species such as humans, domestic animals, fish, beneficial insects and wildlife, while increasing their efficacy to reduce arbovirus outbreak intensity requires targeted scientific data from animal toxicity studies and environmental monitoring activities. Wild birds are an important reservoir host for WNv and are potentially exposed tomore » insecticides used for mosquito control. However, no risk assessments have evaluated whether insecticides augment or extend the potential transmissibility of West Nile virus (WNv) in birds. In order to augment existing resmethrin risk assessments, we aimed to determine whether synergized resmethrin (SR) may cause chickens to develop an elevated or extended WN viremia and if subacute stress may affect its immunotoxicity. We distributed 40 chickens into four groups then exposed them prior to and during WNv infection with SR (50 {mu}g/l resmethrin + 150 {mu}g/l piperonyl butoxide) and/or 20 mg/I corticosterone (CORT) in their drinking-water. Corticosterone was given for 10 continuous days and SR was given for 3 alternate days starting the 3rd day of CORT exposure, then chickens were subcutaneously inoculated with WNv on the 5th day of CORT treatment. Compared to controls, CORT treatment extended and elevated viremia, enhanced WNv-specific antibody and increased the percentage of birds that shed oral virus, whereas SR treatment extended viremia, depressed WNv-specific IgG, and increased the percentage of CORT-treated birds that shed oral virus. Corticosterone and SR independently and interactively altered immunity to WNv in chickens. Further characterization of how variations in SR-exposure to and CORT levels in chickens and wild birds relate to laboratory WNv-infection trials is warranted in order to place these findings into an epidemiological context.« less

Partial protection from organophosphate-induced cholinesterase inhibition by metyrapone treatment.

PubMed

Swiercz, Radosław; Lutz, Piotr; Gralewicz, Sławomir; Grzelińska, Zofia; Piasecka-Zelga, Joanna; Wąsowicz, Wojciech

2013-08-01

Organophosphates are cholinesterase (ChE) inhibitors with worldwide use as insecticides. Stress response, evidenced by a dramatic and relatively long-lasting (several hours) rise in the plasma glucocorticoid concentration is an integral element of the organophosphate (OP) poisoning symptomatology. In rodents, corticosterone (CORT) is the main glucocorticoid. There are several reports suggesting a relationship between the stressor-induced rise in CORT concentration (the CORT response) and the activity of the cerebral and peripheral ChE. Thus, it seems reasonable to presume that, in OP intoxication, the rise in plasma CORT concentration may somehow affect the magnitude of the OP-induced ChE inhibition. Metyrapone (MET) [2-methyl-1,2-di(pyridin-3-yl)propan-1-one] blocks CORT synthesis by inhibiting steroid 11β-hydroxylase, thereby preventing the CORT response. Chlorfenvinphos (CVP) [2-chloro-1-(2,4-dichlorophenyl) ethenyl diethyl phosphate] is an organophosphate insecticide still in use in some countries. The purpose of the present work was to compare the CVP-induced effects - the rise of the plasma CORT concentration and the reduction in ChE activity - in MET-treated and MET-untreated rats. Chlorfenvinphos was administered once at 0.0, 0.5, 1.0 and 3.0 mg/kg i.p. Metyrapone, at 100 mg/kg i.p., was administered five times, at 24-h intervals. The first MET dose was given two hours before CVP. The following was observed in the MET-treated rats: i) no rise in plasma CORT concentration after the CVP administration, ii) a reduced inhibition and a faster restitution of blood and brain ChE activities. The results suggest that MET treatment may confer significant protection against at least some effects of OP poisoning. The likely mechanism of the protective MET action has been discussed.

Blunted Hypothalamo-pituitary Adrenal Axis Response to Predator Odor Predicts High Stress Reactivity

PubMed Central

Whitaker, Annie M.; Gilpin, Nicholas W.

2015-01-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as ‘Avoiders’ or Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24 hours and 11 days), anxiety-like behavior (48 hours and 5 days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24 hours that persisted 11 days post-stress. Both Avoiders and Non-Avoiders exhibited heightened anxiety-like behavior at 48 hours and 5 days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and builds on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. PMID:25824191

Blunted hypothalamo-pituitary adrenal axis response to predator odor predicts high stress reactivity.

PubMed

Whitaker, Annie M; Gilpin, Nicholas W

2015-08-01

Individuals with trauma- and stress-related disorders exhibit increases in avoidance of trauma-related stimuli, heightened anxiety and altered neuroendocrine stress responses. Our laboratory uses a rodent model of stress that mimics the avoidance symptom cluster associated with stress-related disorders. Animals are classified as 'Avoiders' or 'Non-Avoiders' post-stress based on avoidance of predator-odor paired context. Utilizing this model, we are able to examine subpopulation differences in stress reactivity. Here, we used this predator odor model of stress to examine differences in anxiety-like behavior and hypothalamo-pituitary adrenal (HPA) axis function in animals that avoid a predator-paired context relative to those that do not. Rats were exposed to predator odor stress paired with a context and tested for avoidance (24h and 11days), anxiety-like behavior (48h and 5days) and HPA activation following stress. Control animals were exposed to room air. Predator odor stress produced avoidance in approximately 65% of the animals at 24h that persisted 11days post-stress. Both Avoiders and Non-Avoiders exhibited a heightened anxiety-like behavior at 48h and 5days post-stress when compared to unstressed Controls. Non-Avoiders exhibited significant increases in circulating adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations immediately following predator odor stress compared to Controls and this response was significantly attenuated in Avoiders. There was an inverse correlation between circulating ACTH/CORT concentrations and avoidance, indicating that lower levels of ACTH/CORT predicted higher levels of avoidance. These results suggest that stress effects on HPA stress axis activation predict long-term avoidance of stress-paired stimuli, and build on previous data showing the utility of this model for exploring the neurobiological mechanisms of trauma- and stress-related disorders. Copyright © 2015. Published by Elsevier Inc.

Repeated thermal stressor causes chronic elevation of baseline corticosterone and suppresses the physiological endocrine sensitivity to acute stressor in the cane toad (Rhinella marina).

PubMed

Narayan, Edward J; Hero, Jean-Marc

2014-04-01

Extreme environmental temperature could impact the physiology and ecology of animals. The stress endocrine axis provides necessary physiological stress response to acute (day-day) stressors. Presently, there are no empirical evidences showing that exposure to extreme thermal stressor could cause chronic stress in amphibians. This could also modulate the physiological endocrine sensitivity to acute stressors and have serious implications for stress coping in amphibians, particularly those living in fragmented and disease prone environments. We addressed this important question using the cane toad (Rhinella marina) model from its introduced range in Queensland, Australia. We quantified their physiological endocrine sensitivity to a standard acute (capture and handling) stressor after exposing the cane toads to thermal shock at 35°C for 30min daily for 34 days. Corticosterone (CORT) responses to the capture and handling protocol were measured on three sampling intervals (days 14, 24, and 34) to determine whether the physiological endocrine sensitivity was maintained or modulated over-time. Two control groups (C1 for baseline CORT measurement only and C2 acute handled only) and two temperature treatment groups (T1 received daily thermal shock up to day 14 only and a recovery phase of 20 days and T2 received thermal shock daily for 34 days). Results showed that baseline CORT levels remained high on day 14 (combined effect of capture, captivity and thermal stress) for both T1 and T2. Furthermore, baseline CORT levels decreased for T1 once the thermal shock was removed after day 14 and returned to baseline by day 29. On the contrary, baseline CORT levels kept on increasing for T2 over the 34 days of daily thermal shocks. Furthermore, the magnitudes of the acute CORT responses or physiological endocrine sensitivity were consistently high for both C1 and T1. However, acute CORT responses for T2 toads were dramatically reduced between days 24 and 34. These novel findings suggest that repeated exposure to extreme thermal stressor could cause chronic stress and consequently suppress the physiological endocrine sensitivity to acute stressors (e.g. pathogenic diseases) in amphibians. Copyright © 2014 Elsevier Ltd. All rights reserved.

Icariin reverses corticosterone-induced depression-like behavior, decrease in hippocampal brain-derived neurotrophic factor (BDNF) and metabolic network disturbances revealed by NMR-based metabonomics in rats.

PubMed

Gong, Meng-Juan; Han, Bin; Wang, Shu-mei; Liang, Sheng-wang; Zou, Zhong-jie

2016-05-10

Previously published reports have revealed the antidepressant-like effects of icariin in a chronic mild stress model of depression and in a social defeat stress model in mice. However, the therapeutic effect of icariin in an animal model of glucocorticoid-induced depression remains unclear. This study aimed to investigate antidepressant-like effect and the possible mechanisms of icariin in a rat model of corticosterone (CORT)-induced depression by using a combination of behavioral and biochemical assessments and NMR-based metabonomics. The depression model was established by subcutaneous injections of CORT for 21 consecutive days in rats, as evidenced by reduced sucrose intake and hippocampal brain-derived neurotrophic factor (BDNF) levels, together with an increase in immobility time in a forced swim test (FST). Icariin significantly increased sucrose intake and hippocampal BDNF level and decreased the immobility time in FST in CORT-induced depressive rats, suggesting its potent antidepressant activity. Moreover, metabonomic analysis identified eight, five and three potential biomarkers associated with depression in serum, urine and brain tissue extract, respectively. These biomarkers are primarily involved in energy metabolism, lipid metabolism, amino acid metabolism and gut microbe metabolism. Icariin reversed the pathological process of CORT-induced depression, partially via regulation of the disturbed metabolic pathways. These results provide important mechanistic insights into the protective effects of icariin against CORT-induced depression and metabolic dysfunction. Copyright © 2016 Elsevier B.V. All rights reserved.

The effects of testosterone on immune function in quail selected for divergent plasma corticosterone response.

PubMed

Roberts, Mark L; Buchanan, Katherine L; Evans, Matthew R; Marin, Raul H; Satterlee, Daniel G

2009-10-01

The immunocompetence handicap hypothesis (ICHH) suggests that the male sex hormone testosterone has a dual effect; it controls the development and expression of male sexually selected signals, and it suppresses the immune system. Therefore only high quality males are able to fully express secondary sexual traits because only they can tolerate the immunosuppressive qualities of testosterone. A modified version of the ICHH suggests that testosterone causes immunosuppression indirectly by increasing the stress hormone corticosterone (CORT). Lines of Japanese quail (Coturnix japonica) selected for divergent responses in levels of plasma CORT were used to test these hypotheses. Within each CORT response line (as well as in a control stock) we manipulated levels of testosterone in castrated quail by treatment with zero (sham), low or high testosterone implants, before testing the birds' humoral immunity and phytohaemagglutinin (PHA)-induced immune response, as well as body condition. The PHA-induced response was not significantly affected by CORT selected line, testosterone treatment or their interaction. There was, however, a significant effect of CORT line on humoral immunity in that the control birds exhibited the greatest antibody production, but there was no significant effect of testosterone manipulation on humoral immunity. The males in the sham implant treatment group had significantly greater mass than the males in the high testosterone group, suggesting a negative effect of high testosterone on general body condition. We discuss these results in the context of current hypotheses in the field of sexual selection.

Baicalin promotes hippocampal neurogenesis via SGK1- and FKBP5-mediated glucocorticoid receptor phosphorylation in a neuroendocrine mouse model of anxiety/depression

PubMed Central

Zhang, Kuo; Pan, Xing; Wang, Fang; Ma, Jie; Su, Guangyue; Dong, Yingxu; Yang, Jingyu; Wu, Chunfu

2016-01-01

Antidepressants increase hippocampal neurogenesis by activating the glucocorticoid receptor (GR), but excessive GR activation impairs hippocampal neurogenesis, suggesting that normal GR function is crucial for hippocampal neurogenesis. Baicalin was reported to regulate the expression of GR and facilitate hippocampal neurogenesis, but the underlying molecular mechanisms are still unknown. In this study, we used the chronic corticosterone (CORT)-induced mouse model of anxiety/depression to assess antidepressant-like effects of baicalin and illuminate possible molecular mechanisms by which baicalin affects GR-mediated hippocampal neurogenesis. We found that oral administration of baicalin (40, 80 or 160 mg/kg) for 4 weeks alleviated several chronic CORT-induced anxiety/depression-like behaviors. Baicalin also increased Ki-67- and DCX-positive cells to restore chronic CORT-induced suppression of hippocampal neurogenesis. Moreover, baicalin normalized the chronic CORT-induced decrease in GR protein levels, the increase in GR nuclear translocation and the increase in GR phosphorylation at Ser203 and Ser211. Finally, chronic CORT exposure increased the level of FK506-binding protein 51 (FKBP5) and of phosphorylated serum- and glucocorticoid-inducible kinase 1 (SGK1) at Ser422 and Thr256, whereas baicalin normalized these changes. Together, our findings suggest that baicalin improves anxiety/depression-like behaviors and promotes hippocampal neurogenesis. We propose that baicalin may normalize GR function through SGK1- and FKBP5-mediated GR phosphorylation. PMID:27502757

The BDNF Val66Met polymorphism regulates glucocorticoid-induced corticohippocampal remodeling and behavioral despair

PubMed Central

Notaras, M; Du, X; Gogos, J; van den Buuse, M; Hill, R A

2017-01-01

The BDNF Val66Met polymorphism has been associated with sensitivity to stress and affective disorders. We therefore sought to model the inter-causality of these relationships under controlled laboratory conditions. We subjected humanized BDNF Val66Met (hBDNFVal66Met) transgenic mice to a history of stress, modeled by chronic late-adolescent corticosterone (CORT) exposure, before evaluating affective-related behavior using the forced-swim test (FST) in adulthood. While hBDNFMet/Met mice had a depression-like phenotype in the FST irrespective of CORT, hBDNFVal/Val wildtype mice had a resilient phenotype but developed an equally robust depressive-like phenotype following CORT. A range of stress-sensitive molecules were studied across the corticohippocampal axis, and where genotype differences occurred following CORT they tended to inversely coincide with the behavior of the hBDNFVal/Val group. Notably, tyrosine hydroxylase was markedly down-regulated in the mPFC of hBDNFVal/Val mice as a result of CORT treatment, which mimicked expression levels of hBDNFMet/Met mice and the FST behavior of both groups. The expression of calretinin, PSD-95, and truncated TrkB were also concomitantly reduced in the mPFC of hBDNFVal/Val mice by CORT. This work establishes BDNFVal66Met genotype as a regulator of behavioral despair, and identifies new biological targets of BDNF genetic variation relevant to stress-inducible disorders such as depression. PMID:28926000

Attenuated Stress Response to Acute Restraint and Forced Swimming Stress in Arginine Vasopressin 1b Receptor Subtype (Avpr1b) Receptor Knockout Mice and Wild-Type Mice Treated with a Novel Avpr1b Receptor Antagonist

PubMed Central

Roper, J A; Craighead, M; O’Carroll, A-M; Lolait, S J

2010-01-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. PMID:20846299

Attenuated stress response to acute restraint and forced swimming stress in arginine vasopressin 1b receptor subtype (Avpr1b) receptor knockout mice and wild-type mice treated with a novel Avpr1b receptor antagonist.

PubMed

Roper, J A; Craighead, M; O'Carroll, A-M; Lolait, S J

2010-11-01

Arginine vasopressin (AVP) synthesised in the parvocellular region of the hypothalamic paraventricular nucleus and released into the pituitary portal vessels acts on the 1b receptor subtype (Avpr1b) present in anterior pituitary corticotrophs to modulate the release of adrenocorticotrophic hormone (ACTH). Corticotrophin-releasing hormone is considered the major drive behind ACTH release; however, its action is augmented synergistically by AVP. To determine the extent of vasopressinergic influence in the hypothalamic-pituitary-adrenal axis response to restraint and forced swimming stress, we compared the stress hormone levels [plasma ACTH in both stressors and corticosterone (CORT) in restraint stress only] following acute stress in mutant Avpr1b knockout (KO) mice compared to their wild-type controls following the administration of a novel Avpr1b antagonist. Restraint and forced swimming stress-induced increases in plasma ACTH were significantly diminished in mice lacking a functional Avpr1b and in wild-type mice that had been pre-treated with Avpr1b antagonist. A corresponding decrease in plasma CORT levels was also observed in acute restraint-stressed knockout male mice, and in Avpr1b-antagonist-treated male wild-type mice. By contrast, plasma CORT levels were not reduced in acutely restraint-stressed female knockout animals, or in female wild-type animals pre-treated with Avpr1b antagonist. These results demonstrate that pharmacological antagonism or inactivation of Avpr1b causes a reduction in the hypothalamic-pituitary-adrenal (HPA) axis response, particularly ACTH, to acute restraint and forced swimming stress, and show that Avpr1b knockout mice constitute a model by which to study the contribution of Avpr1b to the HPA axis response to acute stressors. © 2010 The Authors. Journal of Neuroendocrinology © 2010 Blackwell Publishing Ltd.

Behavioural and physiological responses of birds to environmentally relevant concentrations of an antidepressant

PubMed Central

Bean, Tom G.; Boxall, Alistair B. A.; Lane, Julie; Herborn, Katherine A.; Pietravalle, Stéphane; Arnold, Kathryn E.

2014-01-01

Many wildlife species forage on sewage-contaminated food, for example, at wastewater treatment plants and on fields fertilized with sewage sludge. The resultant exposure to human pharmaceuticals remains poorly studied for terrestrial species. On the basis of predicted exposure levels in the wild, we administered the common antidepressant fluoxetine (FLUOX) or control treatment via prey to wild-caught starlings (Sturnus vulgaris) for 22 weeks over winter. To investigate responses to fluoxetine, birds were moved from their group aviaries into individual cages for 2 days. Boldness, exploration and activity levels showed no treatment effects but controls and FLUOX birds habituated differently to isolation in terms of the concentration of corticosterone (CORT) metabolites in faeces. The controls that excreted higher concentrations of CORT metabolites on day 1 lost more body mass by day 2 of isolation than those which excreted lower levels of CORT metabolites. CORT metabolites and mass loss were unrelated in FLUOX birds. When we investigated the movements of birds in their group aviaries, we found the controls made a higher frequency of visits to food trays than FLUOX birds around the important foraging periods of sunrise and sunset, as is optimal for wintering birds. Although individual variability makes interpreting the sub-lethal endpoints measured challenging, our data suggest that fluoxetine at environmentally relevant concentrations can significantly alter behaviour and physiology. PMID:25405964

Investigating relations among stress, sleep and nail cortisol and DHEA.

PubMed

Doan, Stacey N; DeYoung, Gerrit; Fuller-Rowell, Thomas E; Liu, Cindy; Meyer, Jerrold

2018-03-01

In the current study, we present data investigating the relationships among stress, sleep disturbance, self-control, and levels of cortisol (CORT) and dehydroepiandrosterone (DHEA) in fingernail clippings. Currently, hair CORT is the only routinely used noninvasive, validated, biomarker of chronic exposure to stress-related hormones. Nail clippings represent an important potential alternative sample matrix for assessing chronic hormone exposure, as it offers a different timeline of hormone incorporation than scalp hair, and may be obtainable from populations in which hair either is lacking or is unavailable for cultural reasons. Moreover, there is established precedent for using fingernail clippings to attain biomarker data. However, the value of nail hormone assessment for psychological research is currently unknown due to a paucity of information on the relations between nail hormone concentrations and environmental or psychological variables. In the present study, we collected data from a low income, minority population (N = 47; 97% African American) to demonstrate feasibility and acceptability of nail collection and analysis of the adrenal steroids CORT and DHEA. Participants reported on perceived stress, sleep and self-control abilities. Correlational analyses suggest that exposure to stressful events, disturbances in sleep and waking were associated with higher levels of nail DHEA, while self-control was associated with higher levels of nail CORT. We discuss the potential importance of this methodology for investigating biological, behavioral, and subjective indices of stress and well-being.

Captivity induces hyper-inflammation in the house sparrow (Passer domesticus).

PubMed

Martin, Lynn B; Kidd, Laura; Liebl, Andrea L; Coon, Courtney A C

2011-08-01

Some species thrive in captivity but others exhibit extensive psychological and physiological deficits, which can be a challenge to animal husbandry and conservation as well as wild immunology. Here, we investigated whether captivity duration impacted the regulation of a key innate immune response, inflammation, of a common wild bird species, the house sparrow (Passer domesticus). Inflammation is one of the most commonly induced and fast-acting immune responses animals mount upon exposure to a parasite. However, attenuation and resolution of inflammatory responses are partly coordinated by glucocorticoid hormones, hormones that can be disregulated in captivity. Here, we tested whether captivity duration alters corticosterone regulation and hence the inflammatory response by comparing the following responses to lipopolysaccharide (LPS; a Gram-negative bacteria component that induces inflammation) of birds caught wild and injected immediately versus those held for 2 or 4 weeks in standard conditions: (1) the magnitude of leukocyte immune gene expression [the cytokines, interleukin 1β and interleukin 6, and Toll-like receptor 4 (TLR4)], (2) the rate of clearance of endotoxin, and (3) the release of corticosterone (CORT) in response to endotoxin (LPS). We predicted that captivity duration would increase baseline CORT and thus suppress gene expression and endotoxin clearance rate. However, our predictions were not supported: TLR4 expression increased with time in captivity irrespective of LPS, and cytokine expression to LPS was stronger the longer birds remained captive. Baseline CORT was not affected by captivity duration, but CORT release post-LPS occurred only in wild birds. Lastly, sparrows held captive for 4 weeks maintained significantly higher levels of circulating endotoxin than other groups, perhaps due to leakage of microbes from the gut, but exogenous LPS did not increase circulating levels over the time scale samples were collected. Altogether, captivity appears to have induced a hyper-inflammatory state in house sparrows, perhaps due to disregulation of glucocorticoids, natural microflora or both.

Flexibility in the parental effort of an Arctic-breeding seabird

USGS Publications Warehouse

Harding, A.M.A.; Kitaysky, A.S.; Hall, M.E.; Welcker, J.; Karnovsky, N.J.; Talbot, S.L.; Hamer, K.C.; Gremillet, D.

2009-01-01

Parental investment strategies are considered to represent a trade-off between the benefits of investment in current offspring and costs to future reproduction. Due to their high residual reproductive value, long-lived organisms are predicted to be more reluctant to increase parental effort. 2. We tested the hypothesis that breeding little auks (Alle alle) have a fixed level of reproductive investment, and thus reduce parental effort when costs associated with reproduction increase. 3. To test this hypothesis we experimentally increased the flight costs of breeding little auks via feather clipping. In 2005 we examined changes in the condition of manipulated parents, of the mates of manipulated parents, and of their chick as direct measures of change in parental resource allocation between self-maintenance and current reproduction. In 2007 we increased sample sizes to determine whether there was a physiological cost (elevated corticosterone, CORT) associated with the manipulation. 4. We found that: (i) clipped birds and their mates lost more body mass than controls, but there was no difference in mass loss between members of a pair; (ii) clipped birds had higher CORT levels than control birds; (iii) there were no inter-annual differences in body mass and CORT levels between clipped individuals and their mates at recapture, and (iv) chicks with a clipped parent had lower peak and fledging mass, and higher CORT levels than control chicks in both years. 5. Contrary to our hypothesis, the reduction in body mass of partners to clipped birds suggests that little auks can increase parental effort to some extent. Nonetheless, the lower fledging mass and higher CORT of chicks with a clipped parent indicates provisioning rates may not have been fully maintained. 6. As predicted by life-history theory, there may be a threshold to the additional reproductive costs breeders will accept, with parents prioritizing self-maintenance over increased provisioning effort when foraging costs become too high. ?? 2008 British Ecological Society.

Involvement of PI3K/Akt/FoxO3a and PKA/CREB Signaling Pathways in the Protective Effect of Fluoxetine Against Corticosterone-Induced Cytotoxicity in PC12 Cells.

PubMed

Zeng, Bingqing; Li, Yiwen; Niu, Bo; Wang, Xinyi; Cheng, Yufang; Zhou, Zhongzhen; You, Tingting; Liu, Yonggang; Wang, Haitao; Xu, Jiangping

2016-08-01

The selective serotonin reuptake inhibitor fluoxetine is neuroprotective in several brain injury models. It is commonly used to treat major depressive disorder and related conditions, but its mechanism of action remains incompletely understood. Activation of the phosphatidylinositol-3-kinase/protein kinase B/forkhead box O3a (PI3K/Akt/FoxO3a) and protein kinase A/cAMP-response element binding protein (PKA/CREB) signaling pathways has been strongly implicated in the pathogenesis of depression and might be the downstream target of fluoxetine. Here, we used PC12 cells exposed to corticosterone (CORT) to study the neuroprotective effects of fluoxetine and the involvement of the PI3K/Akt/FoxO3a and PKA/CREB signaling pathways. Our results show that CORT reduced PC12 cells viability by 70 %, and that fluoxetine showed a concentration-dependent neuroprotective effect. Neuroprotective effects of fluoxetine were abolished by inhibition of PI3K, Akt, and PKA using LY294002, KRX-0401, and H89, respectively. Treatment of PC12 cells with fluoxetine resulted in increased phosphorylation of Akt, FoxO3a, and CREB. Fluoxetine also dose-dependently rescued the phosphorylation levels of Akt, FoxO3a, and CREB, following administration of CORT (from 99 to 110, 56 to 170, 80 to 170 %, respectively). In addition, inhibition of PKA and PI3K/Akt resulted in decreased levels of p-CREB, p-Akt, and p-FoxO3a in the presence of fluoxetine. Furthermore, fluoxetine reversed CORT-induced upregulation of p53-upregulated modulator of apoptosis (Puma) and Bcl-2-interacting mediator of cell death (Bim) via the PI3K/Akt/FoxO3a signaling pathway. H89 treatment reversed the effect of fluoxetine on the mRNA level of brain-derived neurotrophic factor, which was decreased in the presence of CORT. Our data indicate that fluoxetine elicited neuroprotection toward CORT-induced cell death that involves dual regulation from PI3K/Akt/FoxO3a and PKA/CREB pathways.

Proximity to a high traffic road: glucocorticoid and life history consequences for nestling white-crowned sparrows.

PubMed

Crino, O L; Van Oorschot, B Klaassen; Johnson, E E; Malisch, J L; Breuner, C W

2011-09-01

Roads have been associated with decreased reproductive success and biodiversity in avian communities and increased physiological stress in adult birds. Alternatively, roads may also increase food availability and reduce predator pressure. Previous studies have focused on adult birds, but nestlings may also be susceptible to the detrimental impacts of roads. We examined the effects of proximity to a road on nestling glucocorticoid activity and growth in the mountain white-crowned sparrow (Zonotrichia leucophrys oriantha). Additionally, we examined several possible indirect factors that may influence nestling corticosterone (CORT) activity secretion in relation to roads. These indirect effects include parental CORT activity, nest-site characteristics, and parental provisioning. And finally, we assessed possible fitness consequences of roads through measures of fledging success. Nestlings near roads had increased CORT activity, elevated at both baseline and stress-induced levels. Surprisingly, these nestlings were also bigger. Generally, greater corticosterone activity is associated with reduced growth. However, the hypothalamic-pituitary-adrenal axis matures through the nestling period (as nestlings get larger, HPA-activation is greater). Although much of the variance in CORT responses was explained by body size, nestling CORT responses were higher close to roads after controlling for developmental differences. Indirect effects of roads may be mediated through paternal care. Nestling CORT responses were correlated with paternal CORT responses and paternal provisioning increased near roads. Hence, nestlings near roads may be larger due to increased paternal attentiveness. And finally, nest predation was higher for nests close to the road. Roads have apparent costs for white-crowned sparrow nestlings--increased predation, and apparent benefits--increased size. The elevation in CORT activity seems to reflect both increased size (benefit) and elevation due to road proximity (cost). Whether or not roads are good or bad for nestlings remains equivocal. However, it is clear that roads affect nestlings; how or if these effects influence adult survival or reproduction remains to be elucidated. Copyright © 2011 Elsevier Inc. All rights reserved.

The Selective Glucocorticoid Receptor Modulator Cort 113176 Reduces Neurodegeneration and Neuroinflammation in Wobbler Mice Spinal Cord.

PubMed

Meyer, Maria; Lara, Agustina; Hunt, Hazel; Belanoff, Joseph; de Kloet, E Ronald; Gonzalez Deniselle, Maria Claudia; De Nicola, Alejandro F

2018-06-08

Wobbler mice are experimental models for amyotrophic lateral sclerosis. As such they show motoneuron degeneration, motor deficits, and astrogliosis and microgliosis of the spinal cord. Additionally, Wobbler mice show increased plasma, spinal cord and brain corticosterone levels and focal adrenocortical hyperplasia, suggesting a pathogenic role for glucocorticoids in this disorder. Considering this endocrine background, we examined whether the glucocorticoid receptor (GR) modulator CORT 113176 prevents spinal cord neuropathology of Wobblers. CORT 113176 shows high affinity for the GR, with low or null affinity for other steroid receptors. We employed five-month-old genotyped Wobbler mice that received s.c. vehicle or 30 mg/kg/day for 4 days of CORT 113176 dissolved in sesame oil. The mice were used on the 4th day, 2 h after the last dose of CORT 113176. Vehicle-treated Wobbler mice presented vacuolated motoneurons, increased glial fibrillary acidic protein (GFAP)+ astrocytes and decreased glutamine synthase (GS)+ cells. There was strong neuroinflammation, shown by increased staining for IBA1+ microglia and CD11b mRNA, enhanced expression of tumor necrosis factor-α, its cognate receptor TNFR1, toll-like receptor 4, the inducible nitric oxide synthase, NFkB and the high-mobility group box 1 protein (HMGB1). Treatment of Wobbler mice with CORT 113176 reversed the abnormalities of motoneurons and down-regulated proinflammatory mediators and glial reactivity. Expression of glutamate transporters GLT1 and GLAST mRNAs and GLT1 protein was significantly enhanced over untreated Wobblers. In summary, antagonism of GR with CORT 113176 prevented neuropathology and showed anti-inflammatory and anti-glutamatergic effects in the spinal cord of Wobbler mice. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Chronic antidepressant administration alleviates frontal and hippocampal BDNF deficits in CUMS rat.

PubMed

Zhang, Yang; Gu, Fenghua; Chen, Jia; Dong, Wenxin

2010-12-17

Stress activates the hypothalamo-pituitary-adrenal (HPA) axis, regulates the expression of brain-derived neurotrophic factor (BDNF) in the brain, and mediates mood. Antidepressants alleviate stress and up-regulate BDNF gene expression. In this study, we investigated the effect of chronic unpredictable mild stress (CUMS) and the different kinds of antidepressant treatments on the HPA axis and the BDNF expression in the rat brain. Adult Wistar male rats were exposed to a six-week CUMS procedure and received different antidepressant treatments including venlafaxine, mirtazapine, and fluoxetine. Immunohistochemistry and real-time PCR were used to measure BDNF expression levels in the rat brain, and ELISAs were used to investigate the plasma corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels. CUMS significantly decreased the BDNF protein level in the DG, CA1, and CA3 of the hippocampus and increased plasma CORT level. Chronic antidepressant treatments all significantly increased BDNF protein levels in the hippocampus and the pre-frontal cortex. In addition, venlafaxine and mirtazapine inhibited the increase of plasma CORT level. These results suggested that an increase in the BDNF level in the brain could be a pivotal mechanism of various antidepressants to exert their therapeutic effects. Copyright © 2010 Elsevier B.V. All rights reserved.

Chronic corticosterone administration facilitates aversive memory retrieval and increases GR/NOS immunoreactivity.

PubMed

Santos, Thays B; Céspedes, Isabel C; Viana, Milena B

2014-07-01

Glucocorticoids are stress hormones that mediate the organism's reaction to stress. It has been previously proposed that the facilitation of emotional aversive conditioning induced by these hormones may involve nitric oxide-pathways. The purpose of the present study was to address this question. For that, male Wistar rats were surgically implanted with slow-release corticosterone (CORT) pellets (21 days) and tested in a step-down inhibitory avoidance task. Additional groups of animals were also submitted to the same treatment conditions and on the 21st day of treatment assayed for GR (glucocorticoid receptors)-nNOS (neuronal nitric oxide synthase) immunoreactivity (GRi-nNOSi) or measurements of plasma CORT. Results showed that CORT treatment induced facilitation of step-down inhibitory avoidance. This same treatment also significantly increased CORT plasma levels and GRi in the medial, basolateral and basomedial amygdala, in the paraventricular hypothalamic nucleus (PVN), in the ventral and dorsal dentate gyrus, in the ventral CA1 region and in the dorsal CA1 and CA3 regions. Furthermore, nNOSi and GRi-nNOSi were significantly increased by CORT treatment in the medial amygdala and basolateral amygdaloid complex, in the PVN, subiculum, in the dorsal CA3 region and in the ventral CA1 and CA3 regions. These results indicate that the facilitation of aversive conditioning induced by CORT involves GR-nNOS pathways activation, what may be of relevance for a better understanding of stress-related psychiatric conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Reference levels for corticosterone and immune function in farmed saltwater crocodiles (Crocodylus porosus) hatchlings using current Code of Practice guidelines.

PubMed

Finger, John W; Thomson, Peter C; Adams, Amanda L; Benedict, Suresh; Moran, Christopher; Isberg, Sally R

2015-02-01

To determine reference levels for on-farm stressors on immune responsiveness and growth rate, 253 hatchling crocodiles from 11 known breeding pairs were repeatedly measured and blood sampled during their first year. Plasma corticosterone (CORT) was used to quantify baseline stress levels in captive animals and were found to be lower (mean 1.83±SE 0.16 ng/mL) than previously reported in saltwater crocodile hatchlings. Two tests of immune function were also conducted. Innate constitutive immunity was assessed using bacterial killing assays (BKA) against two bacterial species: Escherichia coli and Providencia rettgeri, whereby the latter causes considerable economic loss to industry from septicaemic mortalities. Although the bactericidal capabilities were different at approximately 4 months old (32±3% for E. coli and 16±4% for P. rettgeri), the differences had disappeared by approximately 9 months old (58±2% and 68±6%, respectively). To assess immune responsiveness to a novel antigen, the inflammatory swelling response caused by phytohaemagglutinin (PHA) injection was assessed but was only significantly different between Samplings 1 and 3 (5% LSD). There were no significant clutch effects for CORT or PHA but there were for both BKA traits. CORT was not significantly associated with growth (head length) or the immune parameters except for P. rettgeri BKA where higher CORT levels were associated with better bactericidal capability. As such, these results suggest that the crocodiles in this study are not stressed, therefore endorsing the management strategies adopted within the Australian industry Code of Practice. Copyright © 2015 Elsevier Inc. All rights reserved.

Urinary androgens and cortisol metabolites in field-sampled bonobos (Pan paniscus).

PubMed

Dittami, John; Katina, Stanislav; Möstl, Erich; Eriksson, Jonas; Machatschke, Ivo H; Hohmann, Gottfried

2008-02-01

Urinary metabolites of androgens and cortisol were measured in free-living male and female bonobos. Sex differences and correlations between adrenal and gonadal steroid excretion were investigated. The immunoreactive concentrations of androgens were measured with two different androgen assays. One assay used a testosterone (T) antibody raised with a 17beta-hydroxy group, and the other employed an antibody raised against a reduced form, 5alpha-androstane-17alpha-ol-3-one-CM (17alpha) with cross reactivity for epitestosterone and 5alpha-androstanedione. Both assays have been used in bonobo and chimpanzee studies where non-invasive techniques were employed. The levels of 17alpha-androgen metabolites were 1.7- and 3-fold higher than those of T-metabolites in males and females. The two androgen assay results correlated in males but not females. There was a sex difference in the T-metabolites measured. Male levels were significantly higher. Levels of 17alpha in the two sexes were similar. Cortisol metabolite levels (CORT) were similar between the sexes. The T-metabolites were significantly correlated with CORT in males but not in females. In females, the 17alpha-androgen metabolites correlated with CORT. This suggests that either androgen secretion or metabolism differs between the sexes. A parsimonious interpretation of the androgen assay cortisol/androgen correlation differences would be that larger components of dehydroepiandrosterone (DHEA), androstenedione or epitestosterone from the adrenal androgens were being excreted and measured in the females. The CORT/T metabolite interactions in males may reflect male-specific social or metabolic endocrine conditions.

Sex-reversed correlation between stress levels and dominance rank in a captive non-breeder flock of crows.

PubMed

Ode, Minami; Asaba, Akari; Miyazawa, Eri; Mogi, Kazutaka; Kikusui, Takefumi; Izawa, Ei-Ichi

2015-07-01

Group living has both benefits and costs to individuals; benefits include efficient acquisition of resources, and costs include stress from social conflicts among group members. Such social challenges result in hierarchical dominance ranking among group members as a solution to avoid escalating conflict that causes different levels of basal stress between individuals at different ranks. Stress-associated glucocorticoid (corticosterone in rodents and birds; CORT) levels are known to correlate with dominance rank in diverse taxa and to covary with various social factors, such as sex and dominance maintenance styles. Although there is much evidence for sex differences in the basal levels of CORT in various species, the correlation of sex differences in basal CORT with dominance rank is poorly understood. We investigated the correlation between CORT metabolites (CM) in the droppings and social factors, including rank and sex, in a captive non-breeder group of crows. In this group, all the single males dominated all the single females, and dominance ranks were stable among single males but relatively unstable among single females. CM levels and rank were significantly correlated in a sex-reversed fashion: males at higher rank (i.e., more dominant) had higher CM, whereas females at higher rank exhibited lower CM. This is the first evidence of sex-reversed patterns of CM-rank correlation in birds. The results suggest that different mechanisms of stress-dominance relationships operate on the sexes in non-breeder crow aggregations; in males, stress is associated with the cost of aggressive displays, whereas females experience subordination stress due to males' overt aggression. Copyright © 2015 Elsevier Inc. All rights reserved.

Should I stay or should I go? Hormonal control of nest abandonment in a long-lived bird, the Adélie penguin.

PubMed

Spée, Marion; Beaulieu, Michaël; Dervaux, Antoine; Chastel, Olivier; Le Maho, Yvon; Raclot, Thierry

2010-11-01

According to life-history theory, long-lived birds should favor their survival over the current reproductive attempt, when breeding becomes too costly. In seabirds, incubation is often associated with spontaneous long-term fasting. Below a threshold in body reserves, hormonal and metabolic shift characteristics of a switch from lipid to protein utilization (phase III, PIII) occur. These metabolic changes are paralleled by nest abandonment and stimulation of refeeding behavior. Parental behavior is then under control of two hormones with opposite effects: corticosterone (CORT) and prolactin which stimulate foraging and incubation behavior, respectively. The aim of this study was to determine the respective role of these two hormones in nest abandonment by Adélie penguins. To this end, plasma hormone levels were measured before egg-laying and at departure from the colony (i.e. when birds were relieved by their partner or abandoned their nest), and related to nutritional state and incubation success. We found that males abandoning their nest in PIII presented high CORT levels and low prolactin levels. Interestingly, males which presented high plasma levels of prolactin in PIII did not abandon. We show that although CORT is the first hormone to be affected by prolonged energy constraints, the combined effects of high CORT and low prolactin levels are necessary for parents to favor self-maintenance and abandon the nest. We provide insights into time-course changes of the endocrine profile as PIII proceeds and report that reaching proteolytic late fasting is not sufficient to induce nest abandonment in a long-lived bird. Copyright © 2010 Elsevier Inc. All rights reserved.

Maternal corticosterone exposure has transgenerational effects on grand-offspring.

PubMed

Khan, Nicola; Peters, Richard A; Richardson, Emily; Robert, Kylie A

2016-11-01

The hormone fluctuations that an animal experiences during ovulation can have lifelong effects on developing offspring. These hormones may act as an adaptive mechanism, allowing offspring to be 'pre-programmed' to survive in an unstable environment. Here, we used a transgenerational approach to examine the effects of elevated maternal corticosterone (CORT) on the future reproductive success of female offspring. We show that female zebra finches (Taeniopygia guttata) exposed to embryonic CORT produce daughters that have equal reproductive success (clutch sizes, fertility, hatching success) compared with the daughters produced from untreated mothers, but their offspring had accelerated post-hatching growth rates and were significantly heavier by nutritional independence. Although there was no significant effect on primary offspring sex ratio, females from CORT-treated mothers produced significantly female-biased clutches by nutritional independence. To the best of our knowledge, this is the first record of a transgenerational sex ratio bias in response to elevated maternal CORT in any avian species. © 2016 The Author(s).

Early life stress increases testosterone and corticosterone and alters stress physiology in zebra finches.

PubMed

Zito, J Bayley; Hanna, Angy; Kadoo, Nora; Tomaszycki, Michelle L

2017-09-01

Early life stress has enduring effects on behavior and physiology. However, the effects on hormones and stress physiology remain poorly understood. In the present study, parents of zebra finches of both sexes were exposed to an increased foraging paradigm from 3 to 33days post hatching. Plasma and brains were collected from chicks at 3 developmental time points: post hatching days 25, 60 and adulthood. Plasma was assayed for testosterone (T), estradiol (E2), and corticosterone (CORT). The paraventricular nucleus of the hypothalamus was assessed for corticotrophin releasing factor (CRH) and glucocorticoid receptor (GR) expression. As expected, body mass was lower in nutritionally stressed animals compared to controls at multiple ages. Nutritionally stressed animals overall had higher levels of CORT than did control and this was particularly apparent in females at post hatching day 25. Nutritionally stressed animals also had a higher number of cells expressing CRH and GR in the paraventricular nucleus of the hypothalamus than did controls. There was an interaction, such that both measures were higher in control animals at PHD 25, but higher in NS animals by adulthood. Females, regardless of treatment, had higher circulating CORT and a higher number of cells expressing CRH than did males. Nutritionally stressed animals also had higher levels of T than did control animals, and this difference was greatest for males at post hatching day 60. There were no effects of nutritional stress on E2. These findings suggest that nutritional stress during development has long-lasting effects on testosterone and stress physiology. Copyright © 2017 Elsevier Inc. All rights reserved.

Catecholamine levels in the brain of rats exposed by inhalation to benzalkonium chloride.

PubMed

Swiercz, Radosław; Grzelińska, Zofia; Gralewicz, Sławomir; Wasowicz, Wojciech

2009-01-01

The aim of the study was to obtain quantitative data on the effect of inhalation exposure to benzalkonium chloride (BAC) on the concentration of catecholamines and their metabolites in selected brain structures. Additionally, concentration of corticosterone (CORT) in plasma was estimated. Wistar rats were subjected to a single (6-hour) or repeated (3 days, 6 h/day) exposure to BAC aerosol at ca. 30 mg/m3. The Waters integrated analytical system of HPLC was used to determine the plasma corticosterone. Qualitative and quantitative determinations of catecholamines and their metabolites: 3,4-dihydroxyphenylacetic (DOPAC) and homovanillic (HVA) acids were performed with the use of the Waters integrity HPLC. The determinations have shown that in the BAC-exposed rats the plasma CORT concentration was several times higher than in the control rats. A significant increase of the concentration of dopamine (DA) (striatum and diencephalon) and noradrenaline (NA) (hippocampus and cerebellum) and a significant reduction of adrenaline (A) level (cortex, hippocampus, striatum and mesencephaloon) was found to occur in the brain of rats exposed to BAC compared to control. In the animals exposed to BAC, the concentration of DOPAC, a DA metabolite, was significantly reduced, but the change occurred mainly in the striatum. This resulted in a significant decrease of the DOPAC/DA and HVA/DA metabolic ratio in this structure. It is assumed that the alterations in the concentration of catecholamines and their metabolites in the BAC-exposed rats were related to the unexpectedly strong and persistent activation of the hypothalamo-pituitary-adrenocortical (HPA) axis evidenced by the high plasma CORT concentration.

Elevated corticosterone levels during the first postpartum period influence subsequent pregnancy outcomes and behaviours of the dam.

PubMed

Wong, J H K; Brummelte, S; Galea, L A M

2011-11-01

Postpartum depression affects 15% of new mothers and previous depressive episodes increase the risk for postpartum depression. Chronic administration of corticosterone (CORT) to dams during the postpartum period causes depressive-like behaviour and has been used as a model of postpartum depression. To better understand the subsequent progress of this model, we examined whether there were persistent effects of CORT treatment during the dam's first postpartum period on maternal care and mood following a subsequent pregnancy. Sprague-Dawley female rats received either sesame oil (control) or CORT (40 mg/kg) injections for 22 days during their first postpartum period. Subsequently, all females were re-mated for a second time and neither group received treatment during the second postpartum period. Maternal care was observed from days 2-8 of each postpartum period and dams were tested in the forced-swim test on days 21 and 22 of the first and days 4 and 21 of the second postpartum period. As expected, the amount of time spent immobile in the forced-swim test was increased in CORT dams at the end of the first postpartum period; however, the amount of time spent immobile was decreased at the end of the second postpartum period relative to oil dams. Furthermore, dams treated with CORT in first postpartum period gave birth to a smaller litter with a larger male/female sex ratio after their second pregnancy. This implies that elevated stress hormone levels during the first postpartum period have a substantial influence on subsequent postpartum behaviour and litter characteristics. Further investigations are necessary to fully understand the effect of parity, experience during first motherhood, and hypothalamic-pituitary-adrenal axis regulation on postpartum depression. © 2011 The Authors. Journal of Neuroendocrinology © 2011 Blackwell Publishing Ltd.

Chronic Corticosterone Exposure Increases Expression and Decreases Deoxyribonucleic Acid Methylation of Fkbp5 in Mice

PubMed Central

Lee, Richard S.; Tamashiro, Kellie L. K.; Yang, Xiaoju; Purcell, Ryan H.; Harvey, Amelia; Willour, Virginia L.; Huo, Yuqing; Rongione, Michael; Wand, Gary S.; Potash, James B.

2010-01-01

There is evidence for hypercortisolemia playing a role in the generation of psychiatric symptoms and for epigenetic variation within hypothalamic-pituitary-adrenal (HPA) axis genes mediating behavioral changes. We tested the hypothesis that expression changes would be induced in Fkbp5 and other HPA axis genes by chronic exposure to corticosterone and that these changes would occur through the epigenetic mechanism of loss or gain of DNA methylation (DNAm). We administered corticosterone (CORT) to C57BL/6J mice via their drinking water for 4 wk and tested for behavioral and physiological changes and changes in gene expression levels using RNA extracted from hippocampus, hypothalamus, and blood for the following HPA genes: Fkbp5, Nr3c1, Hsp90, Crh, and Crhr1. The CORT mice exhibited anxiety-like behavior in the elevated plus maze test. Chronic exposure to CORT also caused a significant decrease in the hippocampal and blood mRNA levels of Nr3c1 and a decrease in Hsp90 in blood and caused an increase in Fkbp5 for all tissues. Differences were seen in Fkbp5 methylation in hippocampus and hypothalamus. To isolate a single-cell type, we followed up with an HT-22 mouse hippocampal neuronal cell line exposed to CORT. After 7 d, we observed a 2.4-fold increase in Fkbp5 expression and a decrease in DNAm. In the CORT-treated mice, we also observed changes in blood DNAm in Fkbp5. Our results suggest DNAm plays a role in mediating effects of glucocorticoid exposure on Fkbp5 function, with potential consequences for behavior. PMID:20668026

Changes in corticosterone concentrations and behavior during Mycoplasma gallisepticum infection in house finches (Haemorhous mexicanus).

PubMed

Love, Ashley C; Foltz, Sarah L; Adelman, James S; Moore, Ignacio T; Hawley, Dana M

2016-09-01

Glucocorticoid stress hormones are important for energy mobilization as well as regulation of the immune system, and thus these hormones are particularly likely to both influence and respond to pathogen infection in vertebrates. In this study, we examined how the glucocorticoid stress response in house finches (Haemorhous mexicanus) interacts with experimental infection of the naturally-occurring bacterial pathogen, Mycoplasma gallisepticum (MG). We also investigated whether infection-induced concentrations of corticosterone (CORT), the primary glucocorticoid in birds, were associated with the expression of sickness behavior, the lethargy typically observed in vertebrates early in infection. We found that experimental infection with MG resulted in significantly higher CORT levels on day 5 post-infection, but this effect appeared to be limited to female house finches only. Regardless of sex, infected individuals with greater disease severity had the highest CORT concentrations on day 5 post-infection. House finches exposed to MG exhibited behavioral changes, with infected birds having significantly lower activity levels than sham-inoculated individuals. However, CORT concentrations and the extent of sickness behaviors exhibited among infected birds were not associated. Finally, pre-infection CORT concentrations were associated with reduced inflammation and pathogen load in inoculated males, but not females. Our results suggest that the house finch glucocorticoid stress response may both influence and respond to MG infection in sex-specific ways, but because we had a relatively low sample size of males, future work should confirm these patterns. Finally, manipulative experiments should be performed to test whether the glucocorticoid stress response acts as a brake on the inflammatory response associated with MG infection in house finches. Copyright © 2016 Elsevier Inc. All rights reserved.

The Effect of Feeding Purified versus Chow Diet on Bone Changes Produced by Hindlimb Suspension of Female Rats

NASA Technical Reports Server (NTRS)

Tou, Janet; Arnaud, Sara B.; Grindeland, Richard; Wade, Charles

2004-01-01

Spaceflight simulation studies use chow diets while spaceflight studies use a semi-purified &et. To determine whether the differences in these diets would affect the changes in unweighted bone, we compared the effects of purified vs chow diet on bone parameters, urinary calcium, plasma estradiol, and urinary corticosterone (CORT) in sexually mature female Sprague-Dawley rats. Rats fed purified AIN-93G or chow diet were kept ambulatory (AMB) or subjected to a spaceflight simulation model of unweighted hindlimbs (HLS) for 38 days. Body mass of treatment groups was similar although food intake and caloric density of the diets differed. Both HLS diet groups showed similar decreases in bone mineral content and mechanical strength in unweighted femurs compared to AMB (p<0.05). However, femur length was lower (p<0.05) in the chow-fed than AIN-93G fed groups. Urinary calcium excretion was greater in chow than AIN-93G fed rats, consistent with the higher level of calcium in the diet. Plasma estradiol was lower in HLS than in AMB fed AIN-93G, but similar in HLS and AMB chow fed groups. Femur mineral content was related to plasma estradiol (r(sup 2) =0.91, p<0.00l). Urinary CORT excretion was increased during initial HLS and elevated in HLS/chow-fed rats. Diets did not appear to affect the osteopenia induced by unweighting, but effects on bone growth, calcium excretion, plasma estradiol and urinary CORT do not support the view that these diets can by used interchangeably in bone studies.

Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction

PubMed Central

Guarnieri, Douglas J.; Brayton, Catherine E.; Richards, Sarah M.; Maldonado-Aviles, Jaime; Trinko, Joseph R.; Nelson, Jessica; Taylor, Jane R.; Gourley, Shannon L.; DiLeone, Ralph J.

2011-01-01

Background Food restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed. Methods Analysis of gene expression profiles in male C57BL6/J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a five day food restriction. Quantitative PCR was used to validate these findings and determine the time-course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by ELISA. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals. Results Brief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to non-restricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state. Conclusions These data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress. PMID:21855858

The impact of water-floating and high-intensity exercise on rat's HPA axis and interleukins concentrations.

PubMed

Wang, Jian; Zhao, Dan; Li, Jie; Wang, Guohong; Hu, Lanping; Shao, Jiaging; Gu, Ping; Du, Hong; Wang, Yangt

2012-09-01

Our studies explore the changes of blood corticosterone (CORT), adrenocorticotropic hormone (ACTH), interleukin (IL)-1β, IL-2, IL-6 concentrations and the pituitary ACTH expression in rats after water floating in the presence or absence of following high-intensity exercise. The rats were randomly assigned into three groups. Group A served as control; Group B received 180 minutes water floating and psychological (fear) stimulation; Group C received the same treatment as Group B in addition and 120-minutes non-stop running. Compared to Group A, Group B showed a significant increase of IL-2 (19.91 ± 2.52 vs. 13.09 ± 3.13 ng/ml, P < 0.05), and IL-6 (0.18 ± 0.08 vs. 0.12 ± 0.05 ng/ml, P < 0.05); Group C demonstrated a significant increase of CORT (977.22 ± 207.36 ng/ml vs. 434.58 ± 110.45 ng/ml, P <0.01) and IL-1β (0.21 ± 0.04 vs. 0.16 ± 0.06 ng/ml, P < 0.05), IL-2 (20.29 ± 4.23 vs. 13.09 ± 3.13 ng/ml, P < 0.05), and IL-6 (0.19 ± 0.03 vs. 0.12 ± 0.05 ng/ml, P < 0.05) levels, and a significant decrease of ACTH (16.95 ± 5.46 vs. 22.96 ± 7.32 pg/ml, P = 0.03). Immunohistochemical staining showed the decreased number of pituitary ACTH-positive cells in both Groups B and C (P < 0.05) as compared to Group A. These results have lead us to believe that acute psychological stress can activate the pituitary-adrenal axis and lead to elevation of serum IL-2, IL-6 concentrations. Combined with high-intensity exercise, it can result in the increase of serum CORT, IL-1β, IL-2, IL-6 levels, and the suppression of ACTH.

Assessment of Safety, Tolerability, Pharmacokinetics, and Pharmacological Effect of Orally Administered CORT125134: An Adaptive, Double-Blind, Randomized, Placebo-Controlled Phase 1 Clinical Study.

PubMed

Hunt, Hazel; Donaldson, Kirsteen; Strem, Mark; Zann, Vanessa; Leung, Pui; Sweet, Suzanne; Connor, Alyson; Combs, Dan; Belanoff, Joseph

2018-05-01

CORT125134 is an orally active, high-affinity, selective antagonist of the glucocorticoid receptor that is being developed for indications that may benefit from the modulation of cortisol activity. This first-in-human study was conducted to evaluate the dose-related safety, tolerability, pharmacokinetics and pharmacological effects of CORT125134 and its active metabolite CORT125201. Eighty-one healthy male or female subjects received a single dose of 5 to 500 mg CORT125134 or matching placebo across 9 cohorts; 1 cohort received 150 mg CORT125134 after a high-fat breakfast; and 46 subjects received 50 to 500 mg CORT125134 or matching placebo once daily for up to 14 days across 4 cohorts. CORT125134 was well tolerated at doses up to 250 mg per day for 14 days. CORT125134 was absorbed rapidly and eliminated with a mean half-life ranging from 11 to 19 hours. Steady state was achieved by day 7. Exposure increased in a greater than proportional manner, particularly at lower doses. Exposure to CORT125201 at steady state was less than 5% that of parent CORT125134. Evidence for the desired pharmacological effect (glucocorticoid receptor antagonism) was demonstrated by the ability of CORT125134 to prevent several effects of the glucocorticoid receptor agonist prednisone. © 2018 The Authors. Clinical Pharmacology in Drug Development Published by Wiley Periodicals, Inc. on behalf of The American College of Clinical Pharmacology.

Elevated temperatures are associated with stress in rooftop-nesting Common Nighthawk (Chordeiles minor) chicks.

PubMed

Newberry, Gretchen N; Swanson, David L

2018-01-01

Grasslands and riparian forests in southeastern South Dakota have been greatly reduced since historical times, primarily due to conversion to row-crop agriculture. Common Nighthawk ( Chordeiles minor ) nesting habitat includes grasslands, open woodlands and urban rooftops, but nesting sites in southeastern South Dakota are confined to rooftops, as natural nesting habitat is limited. Nighthawks nesting on exposed rooftop habitats may encounter thermal conditions that increase operative temperatures relative to vegetated land cover types. Mean humidity has increased and mean wind speed and cloud cover have decreased during the nighthawk breeding season from 1948 to 2016 in southeastern South Dakota. These changes might contribute to increasing operative temperatures at exposed rooftop nest sites and this could influence chick condition. We studied nest micro-climate and the plasma stress response for 24 rooftop-nesting nighthawk chicks from 17 nests during 2015 and 2016. High humidity prior to blood collection reduced both baseline and stress-induced plasma corticosterone (CORT). In contrast, high maximum temperatures during the day before sampling increased stress-induced CORT. The magnitude of the chick stress response was significantly negatively related to maximum wind speed for the week prior to CORT measurement. Other weather and micro-climate variables were not significant effectors of CORT metrics. Most chicks had low baseline CORT and were able to mount a stress response, but a subset of chicks ( n = 4) showed elevated baseline CORT and a negative association between the magnitude of stress response and ambient temperature. For this subset, mean ambient temperature for the day before sampling was significantly higher (2.3°C) than for chicks with typical baseline CORT levels. These data suggest that regional climate change trends could affect the ability of nighthawk chicks to mount a stress response, which, in turn, might influence the susceptibility of nighthawk chicks to climate change in the Northern Prairie region.

Elevated plasma corticosterone concentrations influence the onset of rigor mortis and meat color in broilers.

PubMed

Kannan, G; Heath, J L; Wabeck, C J; Owens, S L; Mench, J A

1998-02-01

This experiment was conducted to determine the effect of elevated plasma corticosterone (CORT) levels on meat quality characteristics. Male broilers (Arbor Acres) were either 1) fed a diet containing corticosterone (CORT) prior to processing, 2) transported by truck for 3 h before processing, or 3) processed without either of the above treatments. Six crates of birds (10 birds per crate; two crates per treatment) were stunned or killed using CO2 gas. Six birds per crate were processed and blood samples were collected during exsanguination for plasma CORT analysis. Meat samples were collected from carcasses either at 20 min or at 4 h post-mortem. At each sampling time (ST), Pectoralis superficialis samples were collected and either individually quick frozen (IQF) in liquid nitrogen or aged on ice (AOI) for 24 h prior to pH, ratio of inosine to adenosine nucleotides (R-value), cooking loss, shear value, and color analyses. The IQF Biceps femoris samples were used for pH, R-value, color, and heme pigment analysis. Mean (+/- SEM) CORT concentrations were 12.9+/-2.57, 11.7+/-1.38 and 7.9+/-0.79 ng/mL, respectively, in the CORT, transported, and control groups. There were significant treatment by ST (P < 0.05) and ST (P < 0.001) effects on the R-value of IQF P. superficialis samples. The CORT group had the highest L* value (P < 0.01) and the lowest a* value (P < 0.06). There was also a significant main effect of ST on shear values (P < 0.05) of AOI P. superficialis samples, with the means higher at 4 h than at 20 min post-mortem. The R-value of IQF B. femoris samples was markedly influenced by treatment (P < 0.001) and ST (P < 0.001). The results indicate that artificially elevating circulating CORT concentrations results in lighter meat color in broilers.

Hippocampal Neurogenesis and Dendritic Plasticity Support Running-Improved Spatial Learning and Depression-Like Behaviour in Stressed Rats

PubMed Central

Tong, Jian-Bin; Wong, Richard; Ching, Yick-Pang; Qiu, Guang; Tang, Siu-Wa; Lee, Tatia M. C.; So, Kwok-Fai

2011-01-01

Exercise promotes hippocampal neurogenesis and dendritic plasticity while stress shows the opposite effects, suggesting a possible mechanism for exercise to counteract stress. Changes in hippocampal neurogenesis and dendritic modification occur simultaneously in rats with stress or exercise; however, it is unclear whether neurogenesis or dendritic remodeling has a greater impact on mediating the effect of exercise on stress since they have been separately examined. Here we examined hippocampal cell proliferation in runners treated with different doses (low: 30 mg/kg; moderate: 40 mg/kg; high: 50 mg/kg) of corticosterone (CORT) for 14 days. Water maze task and forced swim tests were applied to assess hippocampal-dependent learning and depression-like behaviour respectively the day after the treatment. Repeated CORT treatment resulted in a graded increase in depression-like behaviour and impaired spatial learning that is associated with decreased hippocampal cell proliferation and BDNF levels. Running reversed these effects in rats treated with low or moderate, but not high doses of CORT. Using 40 mg/kg CORT-treated rats, we further studied the role of neurogenesis and dendritic remodeling in mediating the effects of exercise on stress. Co-labelling with BrdU (thymidine analog) /doublecortin (immature neuronal marker) showed that running increased neuronal differentiation in vehicle- and CORT-treated rats. Running also increased dendritic length and spine density in CA3 pyramidal neurons in 40 mg/kg CORT-treated rats. Ablation of neurogenesis with Ara-c infusion diminished the effect of running on restoring spatial learning and decreasing depression-like behaviour in 40 mg/kg CORT-treated animals in spite of dendritic and spine enhancement. but not normal runners with enhanced dendritic length. The results indicate that both restored hippocampal neurogenesis and dendritic remodelling within the hippocampus are essential for running to counteract stress. PMID:21935393

Preventive effects of ginsenoside Rg1 on post-traumatic stress disorder (PTSD)-like behavior in male C57/B6 mice.

PubMed

Wang, Zhongli; Zhu, Kexuan; Chen, Lin; Ou Yang, Liufeng; Huang, Yufang; Zhao, Yunan

2015-09-25

We investigated the preventive effects of Rg1 on a model of mouse post-traumatic stress disorder (PTSD) induced by electric shock combined with situation reminder and explored the underlying mechanism. In the experiment, before the PTSD animal model was developed, Rg1 (10, 5, and 2.5mg/kg) was orally administered for one week. After the animal model was established, PTSD-like behavior was observed using elevated plus maze, black and light box, and open field tests. One hour after the behavior test, all mice were sacrificed, and then serum corticosterone (CORT) and hypothalamus corticotrophin-releasing hormone (CRH) assays were performed. Results showed that Rg1 (5mg/kg) treatments relieved PTSD-like behavior by altering elevated serum corticosterone and hypothalamus CRH levels. By contrast, fluoxetine (3mg/kg) treatment reversed the behavior changes and had no effect on increased CORT and CRH levels. These findings confirmed the preventive effect of Rg1 in PTSD model. Decreasing CORT and CRH levels may be one of the underlying mechanisms. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Gene profiling reveals a role for stress hormones in the molecular and behavioral response to food restriction.

PubMed

Guarnieri, Douglas J; Brayton, Catherine E; Richards, Sarah M; Maldonado-Aviles, Jaime; Trinko, Joseph R; Nelson, Jessica; Taylor, Jane R; Gourley, Shannon L; DiLeone, Ralph J

2012-02-15

Food restriction is known to enhance learning and motivation. The neural mechanisms underlying these responses likely involve alterations in gene expression in brain regions mediating the motivation to feed. Analysis of gene expression profiles in male C57BL/6J mice using whole-genome microarrays was completed in the medial prefrontal cortex, nucleus accumbens, ventral tegmental area, and the hypothalamus following a 5-day food restriction. Quantitative polymerase chain reaction was used to validate these findings and determine the time course of expression changes. Plasma levels of the stress hormone corticosterone (CORT) were measured by enzyme-linked immunosorbent assay. Expression changes were measured in adrenalectomized animals that underwent food restriction, as well as in animals receiving daily injections of CORT. Progressive ratio responding for food, a measure of motivated behavior, was assessed after CORT treatment in restricted and fed animals. Brief food restriction results in an upregulation of peripheral stress responsive genes in the mammalian brain. Time-course analysis demonstrated rapid and persistent expression changes in all four brain regions under study. Administration of CORT to nonrestricted animals was sufficient to induce a subset of the genes, and alterations in gene expression after food restriction were dependent on intact adrenal glands. CORT can increase the motivation to work for food only in the restricted state. These data demonstrate a central role for CORT in mediating both molecular and behavioral responses to food restriction. The stress hormone-induced alterations in gene expression described here may be relevant for both adaptive and pathological responses to stress. Copyright © 2012 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Minireview: Hair Cortisol: A Novel Biomarker of Hypothalamic-Pituitary-Adrenocortical Activity

PubMed Central

Novak, Melinda A.

2012-01-01

Activity of the hypothalamic-pituitary-adrenocortical (HPA) axis is commonly assessed by measuring glucocorticoids such as cortisol (CORT). For many years, CORT was obtained primarily from blood plasma or urine, whereas later approaches added saliva and feces for noninvasive monitoring of HPA functioning. Despite the value of all these sample matrices for answering many research questions, they remain limited in the temporal range of assessment. Plasma and saliva are point samples that vary as a function of circadian rhythmicity and are susceptible to confounding by environmental disturbances. Even urine and feces generally assess HPA activity over a period of only 24 h or less. We and others have recently developed and validated methods for measuring the concentration of CORT in the body hair of animals (e.g. rhesus monkeys) and scalp hair of humans. CORT is constantly deposited in the growing hair shaft, as a consequence of which such deposition can serve as a biomarker of integrated HPA activity over weeks and months instead of minutes or hours. Since the advent of this methodological advance, hair CORT has already been used as an index of chronic HPA activity and stress in human clinical and nonclinical populations, in a variety of laboratory-housed and wild-living animal species, and in archival specimens that are many decades or even centuries old. Moreover, because human hair is known to grow at an average rate of about 1 cm/month, several studies suggest that CORT levels in hair segments that differ in proximity to the scalp can, under certain conditions, be used as a retrospective calendar of HPA activity during specific time periods preceding sample collection. PMID:22778226

Corticosterone administration after a single-trial contextual fear conditioning does not influence the strength and specificity of recent and remote memory in rats.

PubMed

Bueno, Ana Paula A; de Paiva, Joselisa Péres Queiroz; Corrêa, Moisés Dos Santos; Tiba, Paula Ayako; Fornari, Raquel Vecchio

2017-03-15

It is well established that corticosterone (CORT) enhances memory consolidation of emotionally arousing experiences. Despite emotional memories being usually referred to as well remembered for long periods, there are no studies that have investigated the effects of CORT in modulating the duration and specificity of memory. In the present study, we trained Wistar rats in a single-trial contextual fear conditioning protocol and injected CORT (0.3, 1.0 or 3.0mg/kg), immediately after training, to investigate its effects on memory consolidation. Rats were tested 2 and 29days after the training session or only 29days after training to assess recent or remote memory. Our results show that animals tested for recent memory discriminated the training context from a novel one, while those tested only for remote memory generalized the fear response to both contexts. Animals tested for remote memory after being tested for recent memory were able to discriminate both contexts. These results support the literature regarding memory specificity and duration. However, CORT treatment, even at the dose of 1.0mg/kg that effectively enhanced the plasmatic hormone levels, did not affect the strength or the specificity of memory in either recent or remote memory tests. We hypothesize that the lack of effect of CORT treatment could be due to the low arousing training experience of the single-trial protocol which, despite being sufficient to induce significant recent and remote memory consolidation, may not be sufficient to allow the memory-enhancing effect of CORT. Copyright © 2017 Elsevier Inc. All rights reserved.

Stress hormones mediate predator-induced phenotypic plasticity in amphibian tadpoles

PubMed Central

Middlemis Maher, Jessica; Werner, Earl E.; Denver, Robert J.

2013-01-01

Amphibian tadpoles display extensive anti-predator phenotypic plasticity, reducing locomotory activity and, with chronic predator exposure, developing relatively smaller trunks and larger tails. In many vertebrates, predator exposure alters activity of the neuroendocrine stress axis. We investigated predator-induced effects on stress hormone production and the mechanistic link to anti-predator defences in Rana sylvatica tadpoles. Whole-body corticosterone (CORT) content was positively correlated with predator biomass in natural ponds. Exposure to caged predators in mesocosms caused a reduction in CORT by 4 hours, but increased CORT after 4 days. Tadpoles chronically exposed to exogenous CORT developed larger tails relative to their trunks, matching morphological changes induced by predator chemical cue; this predator effect was blocked by the corticosteroid biosynthesis inhibitor metyrapone. Tadpole tail explants treated in vitro with CORT increased tissue weight, suggesting that CORT acts directly on the tail. Short-term treatment of tadpoles with CORT increased predation mortality, likely due to increased locomotory activity. However, long-term CORT treatment enhanced survivorship, likely due to induced morphology. Our findings support the hypothesis that tadpole physiological and behavioural/morphological responses to predation are causally interrelated. Tadpoles initially suppress CORT and behaviour to avoid capture, but increase CORT with longer exposure, inducing adaptive phenotypic changes. PMID:23466985

Developmental stress increases reproductive success in male zebra finches.

PubMed

Crino, Ondi L; Prather, Colin T; Driscoll, Stephanie C; Good, Jeffrey M; Breuner, Creagh W

2014-11-22

There is increasing evidence that exposure to stress during development can have sustained effects on animal phenotype and performance across life-history stages. For example, developmental stress has been shown to decrease the quality of sexually selected traits (e.g. bird song), and therefore is thought to decrease reproductive success. However, animals exposed to developmental stress may compensate for poor quality sexually selected traits by pursuing alternative reproductive tactics. Here, we examine the effects of developmental stress on adult male reproductive investment and success in the zebra finch (Taeniopygia guttata). We tested the hypothesis that males exposed to developmental stress sire fewer offspring through extra-pair copulations (EPCs), but invest more in parental care. To test this hypothesis, we fed nestlings corticosterone (CORT; the dominant avian stress hormone) during the nestling period and measured their adult reproductive success using common garden breeding experiments. We found that nestlings reared by CORT-fed fathers received more parental care compared with nestlings reared by control fathers. Consequently, males fed CORT during development reared nestlings in better condition compared with control males. Contrary to the prediction that developmental stress decreases male reproductive success, we found that CORT-fed males also sired more offspring and were less likely to rear non-genetic offspring compared with control males, and thus had greater overall reproductive success. These data are the first to demonstrate that developmental stress can have a positive effect on fitness via changes in reproductive success and provide support for an adaptive role of developmental stress in shaping animal phenotype. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

Corticosterone and decision-making in male Wistar rats: the effect of corticosterone application in the infralimbic and orbitofrontal cortex.

PubMed

Koot, Susanne; Koukou, Magdalini; Baars, Annemarie; Hesseling, Peter; van 't Klooster, José; Joëls, Marian; van den Bos, Ruud

2014-01-01

Corticosteroid hormones, released after stress, are known to influence neuronal activity and produce a wide range of effects upon the brain. They affect cognitive tasks including decision-making. Recently it was shown that systemic injections of corticosterone (CORT) disrupt reward-based decision-making in rats when tested in a rat model of the Iowa Gambling Task (rIGT), i.e., rats do not learn across trial blocks to avoid the long-term disadvantageous option. This effect was associated with a change in neuronal activity in prefrontal brain areas, i.e., the infralimbic (IL), lateral orbitofrontal (lOFC) and insular cortex, as assessed by changes in c-Fos expression. Here, we studied whether injections of CORT directly into the IL and lOFC lead to similar changes in decision-making. As in our earlier study, CORT was injected during the final 3 days of the behavioral paradigm, 25 min prior to behavioral testing. Infusions of vehicle into the IL led to a decreased number of visits to the disadvantageous arm across trial blocks, while infusion with CORT did not. Infusions into the lOFC did not lead to differences in the number of visits to the disadvantageous arm between vehicle treated and CORT treated rats. However, compared to vehicle treated rats of the IL group, performance of vehicle treated rats of the lOFC group was impaired, possibly due to cannulation/infusion-related damage of the lOFC affecting decision-making. Overall, these results show that infusions with CORT into the IL are sufficient to disrupt decision-making performance, pointing to a critical role of the IL in corticosteroid effects on reward-based decision-making. The data do not directly support that the same holds true for infusions into the lOFC.

Activation of the HPA Axis and Depression of Feeding Behavior Induced by Restraint Stress Are Separately Regulated by PACAPergic Neurotransmission in the Mouse

PubMed Central

Jiang, Sunny Zhihong; Eiden, Lee E.

2016-01-01

We measured serum CORT elevation in wild-type and PACAP-deficient C57Bl/6N male mice after acute (1 hr) or prolonged (2–3 hr) daily restraint stress for seven days. The PACAP-dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2 and 3 hr of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 hrs daily restraint. Hypophagia induced by 1-hr daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 hours. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 hr) but not acute (1 hr) single-exposure restraint stress, while hypophagia induced by either a single 1 hr or a single 3 hr restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP’s actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-hr restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress. PMID:27228140

Activation of the HPA axis and depression of feeding behavior induced by restraint stress are separately regulated by PACAPergic neurotransmission in the mouse.

PubMed

Jiang, Sunny Zhihong; Eiden, Lee E

2016-07-01

We measured serum CORT elevation in wild-type and PACAP-deficient C57BL/6N male mice after acute (1 h) or prolonged (2-3 h) daily restraint stress for 7 d. The PACAP dependence of CORT elevation was compared to that of stress-induced hypophagia. Daily restraint induced unhabituated peak CORT elevation, and hypophagia/weight loss, of similar magnitude for 1, 2, and 3 h of daily restraint, in wild-type mice. Peak CORT elevation, and hypophagia, were both attenuated in PACAP-deficient mice for 2 and 3 h daily restraint. Hypophagia induced by 1-h daily restraint was also greatly reduced in PACAP-deficient mice, however CORT elevation, both peak and during recovery from stress, was unaffected. Thus, hypothalamic PACAPergic neurotransmission appears to affect CRH gene transcription and peptide production, but not CRH release, in response to psychogenic stress. A single exposure to restraint sufficed to trigger hypophagia over the following 24 h. PACAP deficiency attenuated HPA axis response (CORT elevation) to prolonged (3 h) but not acute (1 h) single-exposure restraint stress, while hypophagia induced by either a single 1 h or a single 3 h restraint were both abolished in PACAP-deficient mice. These results suggest that PACAP's actions to promote suppression of food intake following an episode of psychogenic stress is unrelated to the release of CRH into the portal circulation to activate the pituitary-adrenal axis. Furthermore, demonstration of suppressed food intake after a single 1-h restraint stress provides a convenient assay for investigating the location of the synapses and circuits mediating the effects of PACAP on the behavioral sequelae of psychogenic stress.

[Effects of electroacupuncture with branch-foundation acupoint combination on the pituitary-target gland axis in aging rats with yang deficiency].

PubMed

Hao, Qing; Wu, Song; Liu, Jian-min; Wang, Hua

2014-10-01

To observe the effects of electroacupuncture (EA) with branch-foundation acupoint combination on the indices regarding pituitary-target gland axis in aging rats with yang deficiency, so as to explore its regulating mechanism on aging rats with yang deficiency. Forty healthy Sprague-Dawley female rats were randomly divided into a normal control group, a model group, an EA group and an EA control group, 10 rats in each group. Except the normal control group, the rats in the rest 3 groups were all treated with subcutaneous injection of D-galactose for 40 d, followed by intramuscular injection of hydrocortisone for 7 d to establish aging model with yang deficiency. After the successful establishment of model, the EA group was treated with EA at "Guanyuan" (CV 4), "Housanli" (ST 36) and "Baihui "(GV 20) while the EA control group was treated with EA at "Zhongji" (CV 3) "Yinlingquan" (SP 9) and "Yintang" (GV 29); the rats in the normal control group and model group were immobilized and fixed during the same time period. The treatments were given 6 times per week totally for 4 weeks. With radiation immunity analysis method, the 8 biological indices of pituitary-target gland axis, including thyroid-stimulating hormone (TSH), triiodothyronine (T3), tetraiodothyronine-4 (T4), adrenocorticotropic hormone (ACTH), corticosterone (CORT), estradiol (E2), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were detected to observe the changes of their content. Compared with the normal control group, the serum level of TSH, T3, T4 and E2 were reduced in the model group (P<0.05, P< 0.01) while those of ACTH, CORT, FSH and LH were increased (P<0.05, P<0.01). Compared with the model group, the serum level of TSH, T3, T4 and E2 were increased in the EA group (P<0.05, P<0.01) while those of ACTH, CORT, FSH and LH were significantly reduced (P<0.05, P<0.01). Compared with the EA control group, the content of TSH was increased in the EA group without statistical significance (P>0.05), that of T3, T4 and E2 was increased (all P<0.05) and that of ACTH, CORT, FSH and LH was significantly reduced (all P<0.05). The electroacupuncture with branch-foundation acupoint combination has benign regulating effects on the key hormones of pituitary-target gland axis, which could effectively improve the dysfunction of pituitary-target gland axis that is caused by aging with yang deficiency; the efficacy of electroacupuncture with branch-foundation acupoint combination is superior to that of adjacent control acupoint combination.

Abstinence from prolonged ethanol exposure affects plasma corticosterone, glucocorticoid receptor signaling and stress-related behaviors.

PubMed

Somkuwar, Sucharita S; Vendruscolo, Leandro F; Fannon, McKenzie J; Schmeichel, Brooke E; Nguyen, Tran Bao; Guevara, Jasmin; Sidhu, Harpreet; Contet, Candice; Zorrilla, Eric P; Mandyam, Chitra D

2017-10-01

Alcohol dependence is linked to dysregulation of the hypothalamic-pituitary-adrenal axis. Here, we investigated effects of repeated ethanol intoxication-withdrawal cycles (using chronic intermittent ethanol vapor inhalation; CIE) and abstinence from CIE on peak and nadir plasma corticosterone (CORT) levels. Irritability- and anxiety-like behaviors as well as glucocorticoid receptors (GR) in the medial prefrontal cortex (mPFC) were assessed at various intervals (2h-28d) after cessation of CIE. Results show that peak CORT increased during CIE, transiently decreased during early abstinence (1-11d), and returned to pre-abstinence levels during protracted abstinence (17-27d). Acute withdrawal from CIE enhanced aggression- and anxiety-like behaviors. Early abstinence from CIE reduced anxiety-like behavior. mPFC-GR signaling (indexed by relative phosphorylation of GR at Ser211) was transiently decreased when measured at time points during early and protracted abstinence. Further, voluntary ethanol drinking in CIE (CIE-ED) and CIE-naïve (ED) rats, and effects of CIE-ED and ED on peak CORT levels and mPFC-GR were investigated during acute withdrawal (8h) and protracted abstinence (28d). CIE-ED and ED increased peak CORT during drinking. CIE-ED and ED decreased expression and signaling of mPFC-GR during acute withdrawal, an effect that was reversed by systemic mifepristone treatment. CIE-ED and ED demonstrate robust reinstatement of ethanol seeking during protracted abstinence and show increases in mPFC-GR expression. Collectively, the data demonstrate that acute withdrawal from CIE produces robust alterations in GR signaling, CORT and negative affect symptoms which could facilitate excessive drinking. The findings also show that CIE-ED and ED demonstrate enhanced relapse vulnerability triggered by ethanol cues and these changes are partially mediated by altered GR expression in the mPFC. Taken together, transition to alcohol dependence could be accompanied by alterations in mPFC stress-related pathways that may increase negative emotional symptoms and increase vulnerability to relapse. Copyright © 2017 Elsevier Ltd. All rights reserved.

PGE2 suppresses NK activity in vivo directly and through adrenal hormones: Effects that cannot be reflected by ex-vivo assessment of NK cytotoxicity

PubMed Central

Meron, G.; Tishler, Y.; Shaashua, L.; Rosenne, E.; Levi, B.; Melamed, R.; Gotlieb, N.; Matzner, P.; Sorski, L.; Ben-Eliyahu, S.

2013-01-01

Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE2 administration. In vivo and ex-vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex-vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE2 on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE2 are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex-vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex-vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs. PMID:23153554

PGE2 suppresses NK activity in vivo directly and through adrenal hormones: effects that cannot be reflected by ex vivo assessment of NK cytotoxicity.

PubMed

Meron, G; Tishler, Y; Shaashua, L; Rosenne, E; Levi, B; Melamed, R; Gotlieb, N; Matzner, P; Sorski, L; Ben-Eliyahu, S

2013-02-01

Surgery can suppress in vivo levels of NK cell cytotoxicity (NKCC) through various mechanisms, including catecholamine-, glucocorticoid (CORT)-, and prostaglandin (PG)-mediated responses. However, PGs are synthesized locally following tissue damage, driving proinflammatory and CORT responses, while their systemic levels are often unaffected. Thus, we herein studied the role of adrenal factors in mediating in vivo effects of PGs on NKCC, using adrenalectomized and sham-operated F344 rats subjected to surgery or PGE(2) administration. In vivo and ex vivo approaches were employed, based on intravenous administration of the NK-sensitive MADB106 tumor line, and based on ex vivo assessment of YAC-1 and MADB106 target-line lysis. Additionally, in vitro studies assessed the kinetics of the impact of epinephrine, CORT, and PGE(2) on NKCC. The results indicated that suppression of NKCC by epinephrine and PGE(2) are short lasting, and cannot be evident when these compounds are removed from the in vitro assay milieu, or in the context of ex vivo assessment of NKCC. In contrast, the effects of CORT are long-lasting and are reflected in both conditions even after its removal. Marginating-pulmonary NKCC was less susceptible to suppression than circulating NKCC, when tested against the xenogeneic YAC-1 target line, but not against the syngeneic MADB106 line, which seems to involve different cytotoxicity mechanisms. Overall, these findings indicate that elevated systemic PG levels can directly suppress NKCC in vivo, but following laparotomy adrenal hormones mediate most of the effects of endogenously-released PGs. Additionally, the ex vivo approach seems limited in reflecting the short-lasting NK-suppressive effects of catecholamines and PGs. Copyright © 2012 Elsevier Inc. All rights reserved.

2010 bathymetric survey and digital elevation model of Corte Madera Bay, California

USGS Publications Warehouse

Foxgrover, Amy C.; Finlayson, David P.; Jaffe, Bruce E.; Takekawa, John Y.; Thorne, Karen M.; Spragens, Kyle A.

2011-01-01

A high-resolution bathymetric survey of Corte Madera Bay, California, was collected in early 2010 in support of a collaborative research project initiated by the San Francisco Bay Conservation and Development Commission and funded by the U.S. Environmental Protection Agency. The primary objective of the Innovative Wetland Adaptation in the Lower Corte Madera Creek Watershed Project is to develop shoreline adaptation strategies to future sea-level rise based upon sound science. Fundamental to this research was the development of an of an up-to-date, high-resolution digital elevation model (DEM) extending from the subtidal environment through the surrounding intertidal marsh. We provide bathymetric data collected by the U.S. Geological Survey and have merged the bathymetry with a 1-m resolution aerial lidar data set that was collected by the National Oceanic and Atmospheric Administration during the same time period to create a seamless, high-resolution DEM of Corte Madera Bay and the surrounding topography. The bathymetric and DEM surfaces are provided at both 1 m and 10 m resolutions formatted as both X, Y, Z text files and ESRI Arc ASCII files, which are accompanied by Federal Geographic Data Committee compliant metadata.

Dissociable roles of glucocorticoid and noradrenergic activation on social discounting.

PubMed

Margittai, Zsofia; van Wingerden, Marijn; Schnitzler, Alfons; Joëls, Marian; Kalenscher, Tobias

2018-04-01

People often exhibit prosocial tendencies towards close kin and friends, but generosity decreases as a function of increasing social distance between donor and recipient, a phenomenon called social discounting. Evidence suggests that acute stress affects prosocial behaviour in general and social discounting in particular. We tested the causal role of the important stress neuromodulators cortisol (CORT) and noradrenaline (NA) in this effect by considering two competing hypotheses. On the one hand, it is possible that CORT and NA act in concert to increase generosity towards socially close others by reducing the aversiveness of the cost component in costly altruism and enhancing the emotional salience of vicarious reward. Alternatively, it is equally plausible that CORT and NA exert dissociable, opposing effects on prosocial behaviour based on prior findings implicating CORT in social affiliation, and NA in aggressive and antagonistic tendencies. We pharmacologically manipulated CORT and NA levels in a sample of men (N = 150) and found that isolated hydrocortisone administration promoted prosocial tendencies towards close others, reflected in an altered social discount function, but this effect was offset by concurrent noradrenergic activation brought about by simultaneous yohimbine administration. These results provide inceptive evidence for causal, opposing roles of these two important stress neuromodulators on prosocial behaviour, and give rise to the possibility that, depending on the neuroendocrine response profile, stress neuromodulator action can foster both tend-and-befriend and fight-or-flight tendencies at the same time. Copyright © 2018 Elsevier Ltd. All rights reserved.

The effect of parturition induction treatment on interval to calving, calving ease, postpartum uterine health, and resumption of ovarian cyclicity in beef heifers.

PubMed

Šavc, Miha; Kenny, David A; Beltman, Marijke E

2016-05-01

The aim of this study was to compare the effects of two parturition induction protocols with a nontreated control group, on interval to calving, calving ease, postpartum uterine health, and ovarian cyclicity in beef heifers. At Day 285 of gestation, 81 crossbred recipient beef heifers carrying purebred Simmental fetuses, were blocked by live-weight, body condition score, expected calving date and fetal sex, and assigned to one of three groups: (1) control (CON; no induction treatment, n = 29); (2) induction with corticosteroids (CORT; n = 27); or (3) induction with corticosteroids plus prostaglandin (CORT + PG; n = 25). Interval from induction to calving in hours and calving ease on a scale of 1 to 5 were recorded. Vaginal mucus samples were collected on Day 21 and Day 42 after calving (Day 0) by means of a Metricheck and scored on a scale of 0 to 3. Reproductive tract examinations were conducted on Day 21 and Day 42 after calving, and uterine cytology samples were obtained on Day 21. A positive cytologic sample was defined as greater than 18% neutrophils in the sample obtained via a cytobrush technique. Cows were considered to have resumed ovarian cyclicity if the presence of the CL was confirmed. Data were analyzed using the Mixed (normally distributed data) and Genmod (nonparametric data) procedures of SAS (v. 9.3). The interval from treatment to calving was longer (P < 0.0001) for CON (161.9 ± 15.12 hours) animals compared with CORT (39.7 ± 11.64 hours) or CORT + PG (32.6 ± 12.10 hours), which did not differ. Treatment did not affect calving difficulty score. There was also no difference in incidence of retained placenta between the three groups. At Day 21 postpartum, cytology score tended to be higher for both induced groups (48%) compared with the control animals (24%), but this was not the case for vaginal mucus score (CON 52%, CORT 70%, and CORT + PG 52%). A higher proportion of CON had an involuted uterus by Day 21 postpartum (69%) compared with both induced groups (CORT 48%, CORT + PG 32%). Day 21 ovarian cyclicity was higher in both CON (52%) and CORT (59%) compared with CORT + PG (29%). By Day 42, there was no difference in ovarian cyclicity or uterine involution between CON and CORT; however, a positive relationship was observed between uterine involution score on Day 21 and return to cyclicity on Day 42 in these two groups. There was a negative relationship between uterine involution score and return to cyclicity in the CORT + PG group, and these animals were slower (P < 0.05) to resume cyclicity by Day 42 with a larger proportion animals having evidence of having resumed postpartum ovarian cyclicity in both CON (P = 0.03) and CORT compared with CORT + PG on Day 42. In conclusion, the use of corticosteroid-based treatments is an effective strategy to advance parturition in full term dams and does not have a negative effect on calving progress or dam health. However, when prostaglandin is also included in the protocol, these treatments may lead to greater delay in uterine involution with increased chance of uterine infection and slower resumption of ovarian cyclicity. Copyright © 2016 Elsevier Inc. All rights reserved.

Intracellular glucocorticoid receptors in spleen, but not skin, vary seasonally in wild house sparrows (Passer domesticus)

PubMed Central

Lattin, Christine R.; Waldron-Francis, K.; Romero, L. Michael

2013-01-01

Over the short-term and at physiological doses, acute increases in corticosterone (CORT) titres can enhance immune function. There are predictable seasonal patterns in both circulating CORT and immune function across many animal species, but whether CORT receptor density in immune tissues varies seasonally is currently unknown. Using radioligand binding assays, we examined changes in concentrations of glucocorticoid receptors (GR) and mineralocorticoid receptors (MR) in spleen and skin in wild-caught house sparrows in Massachusetts during six different life-history stages: moult, early winter, late winter, pre-egg-laying, breeding and late breeding. Splenic GR and MR binding were highest during the pre-laying period. This may help animals respond to immune threats through increased lymphocyte proliferation and/or an increase in delayed-type hypersensitivity reactions, both of which CORT can stimulate and in which spleen is involved. A decrease in splenic GR and MR during the late breeding period coincides with low baseline and stress-induced CORT, suggesting immune function in spleen may be relatively CORT-independent during this period. We saw no seasonal patterns in GR or MR in skin, suggesting skin's response to CORT is modulated primarily via changes in circulating CORT titres and/or via local production of CORT in response to wounding and other noxious stimuli. PMID:23407837

Effect of Tyr-MIF-1 peptides on blood ACTH and corticosterone concentration induced by three experimental models of stress.

PubMed

Bocheva, A; Dzambazova, E; Hadjiolova, R; Traikov, L; Mincheva, R; Bivolarski, I

2008-10-01

1. Studies, using a wide variety of stressors, have clearly indicated that the pattern of neuroendocrine response is dependent upon the stress stimulus applied. 2. The Tyr-MIF-1 family of peptides (Tyr-MIF-1s) includes MIF-1, Tyr-MIF-1, Tyr-W-MIF-1 and Tyr-K-MIF-1. These neuropeptides, neuromodulators are able to inhibit the expression of some forms of stress-induced analgesia. 3. The aim of this study was to compare changes in ACTH and corticosterone (CORT) concentration after various stressors (immobilization, cold and heat), as well as after injection of investigated Tyr-MIF-1s peptides. 4. According to our results, hypothalamic-pituitary-adrenal (HPA) system was activated by all the stressors applied. Heat and immobilization are stronger stressors, as the exposure of animals to a high ambient temperature and immobilization resulted in the highest rise of plasma ACTH and CORT concentration when compared with cold stress. Moreover, all the investigated peptides from Tyr-MIF-1 family, administered after application of stressors, inhibited the elevations in adrenocorticotropic hormone (ACTH) and corticosterone (CORT) plasma concentrations significantly. 5. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release. We suggest that Tyr-MIF-1 peptides may possess anti-stressor effects, as they inhibited stress-induced rising in two hormones that were investigated.

Retinoic acid modulates intrahippocampal levels of corticosterone in middle-aged mice: consequences on hippocampal plasticity and contextual memory

PubMed Central

Bonhomme, Damien; Pallet, Véronique; Dominguez, Gaelle; Servant, Laure; Henkous, Nadia; Lafenêtre, Pauline; Higueret, Paul; Béracochéa, Daniel; Touyarot, Katia

2014-01-01

It is now established that vitamin A and its derivatives, retinoic acid (RA), are required for cognitive functions in adulthood. RA hyposignaling and hyperactivity of glucocorticoid (GC) pathway appear concomitantly during aging and would contribute to the deterioration of hippocampal synaptic plasticity and functions. Furthermore, recent data have evidenced counteracting effects of retinoids on GC signaling pathway. In the present study, we addressed the following issue: whether the stimulation of RA pathway could modulate intrahippocampal corticosterone (CORT) levels in middle-aged mice and thereby impact on hippocampal plasticity and cognitive functions. We firstly investigated the effects of vitamin A supplementation and RA treatment in middle-aged mice, on contextual serial discrimination task, a paradigm which allows the detection of early signs of age-related hippocampal-dependent memory dysfunction. We then measured intrahippocampal CORT concentrations by microdialysis before and after a novelty-induced stress. Our results show that both RA treatment and vitamin A supplementation improve “episodic-like” memory in middle-aged mice but RA treatment appears to be more efficient. Moreover, we show that the beneficial effect of RA on memory is associated to an increase in hippocampal PSD-95 expression. In addition, intrahippocampal CORT levels are reduced after novelty-induced stress in RA-treated animals. This effect cannot be related to a modulation of hippocampal 11β-HSD1 expression. Interestingly, RA treatment induces a modulation of RA receptors RARα and RARβ expression in middle-aged mice, a finding which has been correlated with the amplitude of intrahippocampal CORT levels after novelty-induced stress. Taken together, our results suggest that the preventive action of RA treatment on age-related memory deficits in middle-aged mice could be, at least in part, due to an inhibitory effect of retinoids on GC activity. PMID:24570662

Testing the cumulative stress and mismatch hypotheses of psychopathology in a rat model of early-life adversity.

PubMed

Daskalakis, Nikolaos P; Oitzl, Melly S; Schächinger, Hartmut; Champagne, Danielle L; de Kloet, E Ronald

2012-07-16

In the present study, we tested both the cumulative stress and the mismatch hypothesis of psychopathology. For this purpose the combined effects of early-life adversity and later-life stress exposure on behavioral markers of psychosis susceptibility were studied in male Wistar rats. Experiment I: rat pups divided on the basis of the levels of their maternal care experience in low, medium or high maternal care groups, were reared post-weaning in groups (Exp. IA) or in social isolation (Exp. IB) and tested at adulthood under basal conditions or after an acute corticosterone (CORT) administration. Maternal care levels were assessed by measuring the dam's licking and grooming (LG) the first postnatal week of life. Experiment II: rat pups exposed as neonates to daily sessions of 8h of maternal separation (MS) on postnatal days 3, 4 and 5 either altogether in their home cage (HOME SEP) or alone in a novel environment (NOVEL SEP), were reared post-weaning in groups and tested at adulthood under basal conditions. Adult testing included behaviors marking psychosis susceptibility: apomorphine-induced gnawing (APO-gnawing), acoustic startle response and its modulation by a prepulse stimulus (PPI). The behavior of the Medium LG offspring was used as baseline reference for all the three experiments. Experiment I: Low maternal LG history alone had limited effects on the behavior of Wistar offspring, although increased acoustic startle and increased PPI, at high prepulse intensity levels, were observed. When low maternal LG history was combined with post-weaning social isolation, basal APO-gnawing was decreased and PPI increased, compared to High LG and Med LG offspring. This reflects attenuated psychosis susceptibility. High LG offspring reared in isolation displayed, however, the highest APO-gnawing and the lowest PPI levels among rats reared in social isolation, which is indicative for increased psychosis susceptibility. These findings support the mismatch hypothesis. For demonstration of the cumulative stress hypothesis an injection of CORT in the adult Low LG offspring was required that increased APO-gnawing and reduced PPI. This CORT-induced PPI disruption was greatly enhanced after additional isolation rearing. The High LG group, either socially housed or reared in isolation, was resistant to the acute effects of CORT at adulthood. Experiment II: MS increased psychosis susceptibility only in NOVEL SEP rats that had experienced MS in the context of early social isolation. These individuals displayed increased adult APO-gnawing and reduced PPI, if reared post-weaning in a condition that does not match with their early life social environment (i.e. group housing). This finding supports the mismatch hypothesis. The outcome of environmental manipulations on developmental programming of psychosis susceptibility depends on the interplay of early-life adversity and later-life stressors in a manner that supports the mismatch hypothesis. However, evidence for the cumulative stress hypothesis arises if vulnerable individuals are exposed in later life additionally to excess of the stress hormone CORT. Copyright © 2012 Elsevier Inc. All rights reserved.

Divorce in the socially monogamous zebra finch: Hormonal mechanisms and reproductive consequences.

PubMed

Crino, Ondi L; Buchanan, Katherine L; Fanson, Benjamin G; Hurley, Laura L; Smiley, Kristina O; Griffith, Simon C

2017-01-01

Up to 80% of all bird species are socially monogamous. Divorce (switching partners) or pair disruption (due to the death of a partner) has been associated with decreased reproductive success, suggesting social monogamy is a strategy that may maximize fitness via coordination between partners. Previous studies have demonstrated the effects of divorce and pair disruption on immediate reproductive success. Here, we used a paired experimental design in the zebra finch (Taeniopygia guttata) to examine the hormonal mechanisms that modulate parental behavior and reproductive success in response to a partnership change (hereafter divorce). Specifically, we examined the effects of divorce on the avian stress hormone corticosterone (CORT) in both parents and nestlings, parental behaviors (incubation and nestling provisioning), prolactin (PRL), and reproductive success. We found that divorce resulted in delayed clutch initiation, reduced clutch mass, and an increase in nestling CORT response to a standardized stressor. These effects on reproductive investment and chick CORT response were not clearly determined by parental endocrine responses. Divorce had no effect on the level of parental CORT. PRL levels were highly correlated within a pair regardless of treatment, were negatively related to the investment that males made in incubation, and increased in experimental males as a result of pair disruption. This study demonstrates the fundamental impact which divorce has not only on reproduction, but also the physiological stress responses of offspring and suggests that in socially monogamous animals the maintenance of a stable partnership over time could be advantageous for long term fitness. Copyright © 2016 Elsevier Inc. All rights reserved.

Behavioral, physiological, and endocrine responses of starlings to acute increases in density.

PubMed

Nephew, Benjamin C; Romero, L Michael

2003-09-01

One potential stressor to vertebrates both in the wild and in captivity is the presence of numerous individuals in a confined space. To examine the effects of increased conspecific density in birds, we simultaneously measured cardiac, behavioral, and endocrine responses of European starlings (Sturnus vulgaris) to acute crowding. A cage containing a resident bird was outfitted with a trap door that allowed for the introduction of intruder birds (one, three, or five birds) without human interference. The resident bird was implanted with a subcutaneous heart rate (HR) transmitter, behavior was videotaped through a two-way mirror, and blood samples were taken at the end of each treatment to determine plasma corticosterone (CORT) concentrations. Resident starlings significantly increased both general activity and aggressive behaviors while decreasing preening following the initiation of elevated conspecific density. Intruder starlings increased feeding, drinking, and aggressive pecking rates, but postintrusion feeding rates decreased as intruder number increased. Preening decreased in both residents and intruders following the intrusion. HR increased in the resident starlings at the time of intruder introduction, with an increase in the magnitude of this response directly correlating with increasing intruder number. The CORT response to increased density was dependent on social role (resident or intruder), since increasing density did not alter CORT levels in resident birds, but resulted in elevated CORT 30 min following the five-intruder introduction in the intruder birds. Together, these data suggest that increased conspecific density is a significant acute stressor in starlings which is capable of inducing aggression in both residents and intruders. Furthermore, it elicits different responses from different physiological and behavioral systems, and behavioral responses such as feeding and general activity may be density-dependent. The data specifically illustrate that cardiac and behavioral activation can be independent of CORT release, and the CORT response of starlings to increased conspecific density is dependent on social role and degree of the increase in density.

Sex differences in the stress response in SD rats.

PubMed

Lu, Jing; Wu, Xue-Yan; Zhu, Qiong-Bin; Li, Jia; Shi, Li-Gen; Wu, Juan-Li; Zhang, Qi-Jun; Huang, Man-Li; Bao, Ai-Min

2015-05-01

Sex differences play an important role in depression, the basis of which is an excessive stress response. We aimed at revealing the neurobiological sex differences in the same study in acute- and chronically-stressed rats. Female Sprague-Dawley (SD) rats were randomly divided into 6 groups: chronic unpredictable mild stress (CUMS), acute foot shock (FS) and controls, animals in all 3 groups were sacrificed in proestrus or diestrus. Male SD rats were randomly divided into 3 groups: CUMS, FS and controls. Comparisons were made of behavioral changes in CUMS and control rats, plasma levels of corticosterone (CORT), testosterone (T) and estradiol (E2), and of the hypothalamic mRNA-expression of stress-related molecules, i.e. estrogen receptor α and β, androgen receptor, aromatase, mineralocorticoid receptor, glucocorticoid receptor, corticotropin-releasing hormone, arginine vasopressin and oxytocin. CUMS resulted in disordered estrus cycles, more behavioral and hypothalamic stress-related molecules changes and a stronger CORT response in female rats compared with male rats. Female rats also showed decreased E2 and T levels after FS and CUMS, while male FS rats showed increased E2 and male CUMS rats showed decreased T levels. Stress affects the behavioral, endocrine and the molecular response of the stress systems in the hypothalamus of SD rats in a clear sexual dimorphic way, which has parallels in human data on stress and depression. Copyright © 2015 Elsevier B.V. All rights reserved.

Differential Peripheral Proteomic Biosignature of Fluoxetine Response in a Mouse Model of Anxiety/Depression

PubMed Central

Mendez-David, Indira; Boursier, Céline; Domergue, Valérie; Colle, Romain; Falissard, Bruno; Corruble, Emmanuelle; Gardier, Alain M.; Guilloux, Jean-Philippe; David, Denis J.

2017-01-01

The incorporation of peripheral biomarkers in the treatment of major depressive disorders (MDD) could improve the efficiency of treatments and increase remission rate. Peripheral blood mononuclear cells (PBMCs) represent an attractive biological substrate allowing the identification of a drug response signature. Using a proteomic approach with high-resolution mass spectrometry, the present study aimed to identify a biosignature of antidepressant response (fluoxetine, a Selective Serotonin Reuptake Inhibitor) in PBMCs in a mouse model of anxiety/depression. Following determination of an emotionality score, using complementary behavioral analysis of anxiety/depression across three different tests (Elevated Plus Maze, Novelty Suppressed Feeding, Splash Test), we showed that a 4-week corticosterone treatment (35 μg/ml, CORT model) in C57BL/6NTac male mice induced an anxiety/depressive-like behavior. Then, chronic fluoxetine treatment (18 mg/kg/day for 28 days in the drinking water) reduced corticosterone-induced increase in emotional behavior. However, among 46 fluoxetine-treated mice, only 30 of them presented a 50% decrease in emotionality score, defining fluoxetine responders (CORT/Flx-R). To determine a peripheral biological signature of fluoxetine response, proteomic analysis was performed from PBMCs isolated from the “most” affected corticosterone/vehicle (CORT/V), corticosterone/fluoxetine responders and non-responders (CORT/Flx-NR) animals. In comparison to CORT/V, a total of 263 proteins were differently expressed after fluoxetine exposure. Expression profile of these proteins showed a strong similarity between CORT/Flx-R and CORT/Flx-NR (R = 0.827, p < 1e-7). Direct comparison of CORT/Flx-R and CORT/Flx-NR groups revealed 100 differently expressed proteins, representing a combination of markers associated either with the maintenance of animals in a refractory state, or associated with behavioral improvement. Finally, 19 proteins showed a differential direction of expression between CORT/Flx-R and CORT/Flx-NR that drove them away from the CORT-treated profile. Among them, eight upregulated proteins (RPN2, HSPA9, NPTN, AP2B1, UQCRC2, RACK-1, TOLLIP) and one downregulated protein, TLN2, were previously associated with MDD or antidepressant drug response in the literature. Future preclinical studies will be required to validate whether proteomic changes observed in PBMCs from CORT/Flx-R mice mirror biological changes in brain tissues. PMID:28860968

Sustained release of corticosterone in rats affects reactivity, but does not affect habituation to immobilization and acoustic stimuli.

PubMed

Tanke, Marit A C; Fokkema, Dirk S; Doornbos, Bennard; Postema, Folkert; Korf, Jakob

2008-07-18

Depression is often preceded by stressful life events and accompanied with elevated cortisol levels and glucocorticoid resistance. It has been suggested that a major depressive disorder may result from impaired coping with and adaptation to stress. The question is whether or not hypothalamus-pituitary-adrenal (HPA)-axis dysfunction influences the process of adaptation. We examined the effect of a dysregulated HPA-axis on the adaptation to acoustic stimuli in rats with or without preceding restraint stress. HPA-axis function was altered via slow release of corticosterone (CORT, 90 mg) from subcutaneously implanted pellets for 7 or 14 days. The rate of body temperature increases during restraint (10 min) and the response to acoustic stimuli (of 80+120 dB) were used to quantify daily stress reactivity. Rats habituated to either stress regardless of CORT treatment. CORT treatment combined with restraint decreased the initial reactivity and the variability in response, but the rate of habituation was not influenced. These results show that suppressing normal HPA-axis function by chronic exposure to CORT does affect the course of habituation, but not habituation per se. This implies that altered HPA-axis function in depressed patients may not be causally related to stress coping, but instead may influence the course of the disorder.

78 FR 5826 - Proposed Flood Hazard Determinations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

..., 26 Corte Madera Avenue, Mill Valley, CA 94941. City of San Rafael Public Works Department, 111..., CA 94920. Town of Corte Madera Engineering Department, 233 Tamalpais Drive, Corte Madera, CA 94976...

Does feather corticosterone reflect individual quality or external stress in arctic-nesting migratory birds?

PubMed

Legagneux, Pierre; Harms, N Jane; Gauthier, Gilles; Chastel, Olivier; Gilchrist, H Grant; Bortolotti, Gary; Bêty, Joël; Soos, Catherine

2013-01-01

The effects of environmental perturbations or stressors on individual states can be carried over to subsequent life stages and ultimately affect survival and reproduction. The concentration of corticosterone (CORT) in feathers is an integrated measure of hypothalamic-pituitary-adrenal activity during the molting period, providing information on the total baseline and stress-induced CORT secreted during the period of feather growth. Common eiders and greater snow geese replace all flight feathers once a year during the pre-basic molt, which occurs following breeding. Thus, CORT contained in feathers of pre-breeding individuals sampled in spring reflects the total CORT secreted during the previous molting event, which may provide insight into the magnitude or extent of stress experienced during this time period. We used data from multiple recaptures to disentangle the contribution of individual quality vs. external factors (i.e., breeding investment or environmental conditions) on feather CORT in arctic-nesting waterfowl. Our results revealed no repeatability of feather CORT within individuals of either species. In common eiders, feather CORT was not affected by prior reproductive investment, nor by pre-breeding (spring) body condition prior to the molting period. Individual feather CORT greatly varied according to the year, and August-September temperatures explained most of the annual variation in feather CORT. Understanding mechanisms that affect energetic costs and stress responses during molting will require further studies either using long-term data or experiments. Although our study period encompassed only five years, it nonetheless provides evidence that CORT measured in feathers likely reflects responses to environmental conditions experienced by birds during molt, and could be used as a metric to study carry-over effects.

Inhibiting corticosterone synthesis during fear memory formation exacerbates cued fear extinction memory deficits within the single prolonged stress model.

PubMed

Keller, Samantha M; Schreiber, William B; Stanfield, Briana R; Knox, Dayan

2015-01-01

Using the single prolonged stress (SPS) animal model of post-traumatic stress disorder (PTSD), previous studies suggest that enhanced glucocorticoid receptor (GR) expression leads to cued fear extinction retention deficits. However, it is unknown how the endogenous ligand of GRs, corticosterone (CORT), may contribute to extinction retention deficits in the SPS model. Given that CORT synthesis during fear learning is critical for fear memory consolidation and SPS enhances GR expression, CORT synthesis during fear memory formation could strengthen fear memory in SPS rats by enhancing GR activation during fear learning. In turn, this could lead to cued fear extinction retention deficits. We tested the hypothesis that CORT synthesis during fear learning leads to cued fear extinction retention deficits in SPS rats by administering the CORT synthesis inhibitor metyrapone to SPS and control rats prior to fear conditioning, and observed the effect this had on extinction memory. Inhibiting CORT synthesis during fear memory formation in control rats tended to decrease cued freezing, though this effect never reached statistical significance. Contrary to our hypothesis, inhibiting CORT synthesis during fear memory formation disrupted extinction retention in SPS rats. This finding suggests that even though SPS exposure leads to cued fear extinction memory deficits, CORT synthesis during fear memory formation enhances extinction retention in SPS rats. This suggests that stress-induced CORT synthesis in previously stressed rats can be beneficial. Copyright © 2015 Elsevier B.V. All rights reserved.

Effect of reproductive status on hypothalamic-pituitary-adrenal (HPA) activity and reactivity in male California mice (Peromyscus californicus)

PubMed Central

Harris, Breanna N.; Saltzman, Wendy

2013-01-01

Previous studies indicate that reproductive condition can alter the stress response and glucocorticoid release. Although the functional significance of hypothalamic-pituitary-adrenal (HPA) axis modulation by breeding condition is not fully understood, one possible explanation is the behavior hypothesis, which states that an animal’s need to express parental behavior may be driving modulation of the HPA axis. This possibility is consistent with findings of blunted activity and reactivity of the HPA axis in lactating female mammals; however, effects of reproductive status on HPA function have not been well characterized in male mammals that express parental behavior. Therefore, we tested this hypothesis in the monogamous and biparental California mouse. Several aspects of HPA activity were compared in males from three reproductive conditions: virgin males (housed with another male), non-breeding males (housed with a tubally ligated female), and first-time fathers (housed with a female and their first litter of pups). In light of the behavior hypothesis we predicted that new fathers would differ from virgin and non-breeding males in several aspects of HPA function and corticosterone (CORT) output: decreased amplitude of the diurnal rhythm in CORT, a blunted CORT increase following predator-odor stress, increased sensitivity to glucocorticoid negative feedback, and/or a blunted CORT response to pharmacological stimulation. In addition, we predicted that first-time fathers would be more resistant to CORT-induced suppression of testosterone secretion, as testosterone is important for paternal behavior in this species. We found that virgin males, non-breeding males and first-time fathers did not display any CORT differences in diurnal rhythm, response to a predator-odor stressor, or response to pharmacological suppression or stimulation. Additionally, there were no differences in circulating testosterone concentrations. Adrenal mass was, however, significantly lower in new fathers than in virgin or non-breeding males. These results suggest that the behavior hypothesis does not explain HPA function across reproductive conditions in male California mice. PMID:23474132

Repeated exposure to corticosterone increases depression-like behavior in two different versions of the forced swim test without altering nonspecific locomotor activity or muscle strength.

PubMed

Marks, Wendie; Fournier, Neil M; Kalynchuk, Lisa E

2009-08-04

We have recently shown that repeated high dose injections of corticosterone (CORT) reliably increase depression-like behavior on a modified one-day version of the forced swim test. The main purpose of this experiment was to compare the effect of these CORT injections on our one-day version of the forced swim test and the more traditional two-day version of the test. A second purpose was to determine whether altered behavior in the forced swim test could be due to nonspecific changes in locomotor activity or muscle strength. Separate groups of rats received a high dose CORT injection (40 mg/kg) or a vehicle injection once per day for 21 consecutive days. Then, half the rats from each group were exposed to the traditional two-day forced swim test and the other half were exposed to our one-day forced swim test. After the forced swim testing, all the rats were tested in an open field and in a wire suspension grip strength test. The CORT injections significantly increased the time spent immobile and decreased the time spent swimming in both versions of the forced swim test. However, they had no significant effect on activity in the open field or grip strength in the wire suspension test. These results show that repeated CORT injections increase depression-like behavior regardless of the specific parameters of forced swim testing, and that these effects are independent of changes in locomotor activity or muscle strength.

Stress impairs new but not established relationships in seasonally social voles.

PubMed

Anacker, Allison M J; Reitz, Kara M; Goodwin, Nastacia L; Beery, Annaliese K

2016-03-01

Affiliative social relationships are impacted by stressors and can shape responses to stress. However, the effects of stress on social relationships in different contexts are not well understood. Meadow voles provide an opportunity to study these effects on peer relationships outside of a reproductive context. In winter months, female meadow voles cohabit with peers of both sexes, and social huddling is facilitated by exposure to short, winter-like day lengths in the lab. We investigated the role of stress and corticosterone (cort) levels in social behavior in short day-housed female meadow voles. A brief forced swim elevated cort levels, and we assessed the effects of this stressor on new and established relationships between females. In pairs formed following exposure to swim stress, the stressor significantly reduced the fraction of huddling time subjects spent with a familiar partner. Swim stress did not affect partner preferences in pairs established prior to the stressor. Finally, we examined fecal glucocorticoid metabolite levels via immunoassay in voles housed under short day (10h light) versus long day (14 h light) conditions and detected higher glucocorticoid levels in long day-housed voles. These findings support a role for stress regulation in the formation of social relationships in female meadow voles, and are consistent with a potential role for seasonal variation in cort in the behavioral transition from solitary to social. Together they highlight the importance of stress and possibly glucocorticoid signaling for social behavior. Copyright © 2016 Elsevier Inc. All rights reserved.

Boldness behavior and stress physiology in a novel urban environment suggest rapid correlated evolutionary adaptation

PubMed Central

Cardoso, Gonçalo C.; Whittaker, Danielle J.; Campbell-Nelson, Samuel; Robertson, Kyle W.; Ketterson, Ellen D.

2012-01-01

Novel or changing environments expose animals to diverse stressors that likely require coordinated hormonal and behavioral adaptations. Predicted adaptations to urban environments include attenuated physiological responses to stressors and bolder exploratory behaviors, but few studies to date have evaluated the impact of urban life on codivergence of these hormonal and behavioral traits in natural systems. Here, we demonstrate rapid adaptive shifts in both stress physiology and correlated boldness behaviors in a songbird, the dark-eyed junco, following its colonization of a novel urban environment. We compared elevation in corticosterone (CORT) in response to handling and flight initiation distances in birds from a recently established urban population in San Diego, California to birds from a nearby wildland population in the species' ancestral montane breeding range. We also measured CORT and exploratory behavior in birds raised from early life in a captive common garden study. We found persistent population differences for both reduced CORT responses and bolder exploratory behavior in birds from the colonist population, as well as significant negative covariation between maximum CORT and exploratory behavior. Although early developmental effects cannot be ruled out, these results suggest contemporary adaptive evolution of correlated hormonal and behavioral traits associated with colonization of an urban habitat. PMID:22936840

Boldness behavior and stress physiology in a novel urban environment suggest rapid correlated evolutionary adaptation.

PubMed

Atwell, Jonathan W; Cardoso, Gonçalo C; Whittaker, Danielle J; Campbell-Nelson, Samuel; Robertson, Kyle W; Ketterson, Ellen D

2012-09-01

Novel or changing environments expose animals to diverse stressors that likely require coordinated hormonal and behavioral adaptations. Predicted adaptations to urban environments include attenuated physiological responses to stressors and bolder exploratory behaviors, but few studies to date have evaluated the impact of urban life on codivergence of these hormonal and behavioral traits in natural systems. Here, we demonstrate rapid adaptive shifts in both stress physiology and correlated boldness behaviors in a songbird, the dark-eyed junco, following its colonization of a novel urban environment. We compared elevation in corticosterone (CORT) in response to handling and flight initiation distances in birds from a recently established urban population in San Diego, California to birds from a nearby wildland population in the species' ancestral montane breeding range. We also measured CORT and exploratory behavior in birds raised from early life in a captive common garden study. We found persistent population differences for both reduced CORT responses and bolder exploratory behavior in birds from the colonist population, as well as significant negative covariation between maximum CORT and exploratory behavior. Although early developmental effects cannot be ruled out, these results suggest contemporary adaptive evolution of correlated hormonal and behavioral traits associated with colonization of an urban habitat.

Etazolate rescues behavioral deficits in chronic unpredictable mild stress model: modulation of hypothalamic-pituitary-adrenal axis activity and brain-derived neurotrophic factor level.

PubMed

Jindal, Ankur; Mahesh, Radhakrishnan; Bhatt, Shvetank

2013-11-01

Preliminary study in our laboratory showed that etazolate produced antidepressant- and anxiolytic-like effects in rodent models, however, the ability of etazolate to produce antidepressant- and anxiolytic-like effects and underlying mechanism(s) in chronic unpredictable mild stress (CUMS) model have not been adequately addressed. This study was aimed to investigate the beneficial effects of etazolate on CUMS-induced behavioral deficits (depression- and anxiety-like behaviors). In addition, the possible underlying mechanism(s) of etazolate in CUMS model was also investigated by measuring serum corticosterone (CORT) and brain-derived neurotrophic factor (BDNF) levels. Mice were subjected to a battery of stressors for 28 days. Etazolate (0.5 and 1 mg/kg, p.o.) and fluoxetine (20mg/kg, p.o.) were administered during the last 21 days (8-28th) of the CUMS paradigm. The results showed that 4-weeks CUMS produces significant depression-like behavior in tail suspension test (TST) and partial anxiety-like behavior in elevated plus maze (EPM) and open field test (OFT). Stressed mice have also shown a significant high serum CORT and low BDNF level. Chronic treatment with etazolate (0.5 and 1mg/kg., p.o.) and fluoxetine (20mg/kg., p.o.) produced significant antidepressant-like behavior in TST (decreased duration of immobility), whereas, partial anxiolytic-like behavior in EPM (increased percentage of open arm entries) and OFT (increased % central ambulation score, total ambulation score and time spent in center zone). In addition, etazolate and fluoxetine treatment significantly (p<0.05) increased the BDNF level and inhibited the hypothalamic-pituitary-adrenocortical (HPA) axis hyperactivity, as evidenced by low serum CORT level in stressed mice. In addition, etazolate and fluoxetine also showed significant antidepressant- and anxiolytic-like effects in normal control mice. In this study no significant changes were observed in locomotor activity in actophotometer test. Moreover, we did not find any effect of etazolate and fluoxetine on CORT and BDNF levels in normal control mice. In conclusion, the results of the present study suggested compelling evidences that etazolate has more marked effect on depression-like behavior in mice, which is atleast in part may be related to their modulating effects on the HPA axis and BDNF level. Copyright © 2013 Elsevier Ltd. All rights reserved.

Stress responses of adolescent male and female rats exposed repeatedly to cat odor stimuli, and long-term enhancement of adult defensive behaviors.

PubMed

Wright, Lisa D; Muir, Katherine E; Perrot, Tara S

2013-07-01

In order to characterize the short- and long-term effects of repeated stressor exposure during adolescence, and to compare the effects of using two sources of cat odor as stressor stimuli, male and female adolescent rats (postnatal day (PND) ∼ 38-46) were exposed on five occasions to either a control stimulus, a cloth stimulus containing cat hair/dander, or a section of cat collar previously worn by a cat. Relative to control stimulus exposure, activity was suppressed and defensive behavior enhanced during exposure to either cat odor stimulus (most pervasively in rats exposed to the collar). Only cloth-exposed rats showed elevated levels of corticosterone (CORT), and only after repeated stressor exposure, but interestingly, rats exposed to the collar stimulus during adolescence continued to show increased behavioral indices of anxiety in adulthood. In this group, the time an individual spent in physical contact with a cagemate during the final adolescent exposure was negatively related to stress-induced CORT output in adulthood, which suggests that greater use of social support during adolescent stress may facilitate adult behavioral coping, without necessitating increased CORT release. These findings demonstrate that adolescent male and female rats respond defensively to cat odor stimuli across repeated exposures and that exposure to such stressors during adolescence can augment adult anxiety-like behavior in similar stressful conditions. These findings also suggest a potential role for social behavior during adolescent stressor exposure in mediating long-term outcomes. Copyright © 2012 Wiley Periodicals, Inc.

Brain and Serum Androsterone Is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

PubMed Central

Servatius, Richard J.; Marx, Christine E.; Sinha, Swamini; Avcu, Pelin; Kilts, Jason D.; Naylor, Jennifer C.; Pang, Kevin C. H.

2016-01-01

Exposure to lateral fluid percussion (LFP) injury consistent with mild traumatic brain injury (mTBI) persistently attenuates acoustic startle responses (ASRs) in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM). ASRs were measured post injury days (PIDs) 1, 3, 7, 14, 21, and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34), PID 35 (S35), on both days (2S), or the experimental context (CON). Levels of the neurosteroids pregnenolone (PREG), allopregnanolone (ALLO), and androsterone (ANDRO) were determined for the prefrontal cortex, hippocampus, and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30, and 60 min post-stressor for determination of corticosterone (CORT) levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA) receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration. PMID:27616978

Effects of diet and exposure to hindlimb suspension on estrous cycling in Sprague-Dawley rats

NASA Technical Reports Server (NTRS)

Tou, Janet C L.; Grindeland, Richard E.; Wade, Charles E.

2004-01-01

Various factors can disrupt the female reproductive cycle resulting in subfertility. The primary objective of this study was to determine whether physiological changes associated with exposure to hypogravity disrupt reproductive cycles. The hindlimb suspension (HLS) model was used to simulate the major physiological effects of hypogravity in female Sprague-Dawley rats. Also, to determine whether diet may influence reproductive results, rats were fed purified American Institute of Nutrition (AIN)-93G or chow diet. Rats (n = 9-11/group) subjected to HLS had lengthened estrous cycles due to prolonged diestrus, indicating hypoestrogenism. Interestingly, HLS rats fed AIN-93G but not chow diet had significantly reduced time spent in estrus and decreased plasma estradiol. Attenuation of hypoestrogenism in the chow-fed rats suggested that diet provided an exogenous source of estrogen. The mechanism involved in the disruption of estrous cycling remains to be determined. HLS increased urinary corticosterone (CORT) levels during the initial 4 days of HLS, suggesting that physiological responses to acute stress may be a potential mechanism in the disruption of estrous cycles. Higher basal urinary CORT was observed in rats fed chow vs. AIN-93G diet. HLS resulted in increased urinary CORT. However, two-way ANOVA indicated a significant HLS effect (P < 0.001) but no effect of HLS x diet effect on urinary CORT levels, suggesting that estrogenic activity associated with the chow diet did not enhance the stress response. The results of this study indicate that HLS, diet, and the combination of HLS and diet influence estrous cycling. This has important implications for future reproductive success in the hypogravity environment of space.

Interaction of reelin and stress on immobility in the forced swim test but not dopamine-mediated locomotor hyperactivity or prepulse inhibition disruption: Relevance to psychotic and mood disorders.

PubMed

Notaras, Michael J; Vivian, Billie; Wilson, Carey; van den Buuse, Maarten

2017-07-13

Psychotic disorders, such as schizophrenia, as well as some mood disorders, such as bipolar disorder, have been suggested to share common biological risk factors. One such factor is reelin, a large extracellular matrix glycoprotein that regulates neuronal migration during development as well as numerous activity-dependent processes in the adult brain. The current study sought to evaluate whether a history of stress exposure interacts with endogenous reelin levels to modify behavioural endophenotypes of relevance to psychotic and mood disorders. Heterozygous Reeler Mice (HRM) and wildtype (WT) controls were treated with 50mg/L of corticosterone (CORT) in their drinking water from 6 to 9weeks of age, before undergoing behavioural testing in adulthood. We assessed methamphetamine-induced locomotor hyperactivity, prepulse inhibition (PPI) of acoustic startle, short-term spatial memory in the Y-maze, and depression-like behaviour in the Forced-Swim Test (FST). HRM genotype or CORT treatment did not affect methamphetamine-induced locomotor hyperactivity, a model of psychosis-like behaviour. At baseline, HRM showed decreased PPI at the commonly used 100msec interstimulus interval (ISI), but not at the 30msec ISI or following challenge with apomorphine. A history of CORT exposure potentiated immobility in the FST amongst HRM, but not WT mice. In the Y-maze, chronic CORT treatment decreased novel arm preference amongst HRM, reflecting reduced short-term spatial memory. These data confirm a significant role of endogenous reelin levels on stress-related behaviour, supporting a possible role in both bipolar disorder and schizophrenia. However, an interaction of reelin deficiency with dopaminergic regulation of psychosis-like behaviour remains unclear. Copyright © 2017 Elsevier B.V. All rights reserved.

The neuroinflammatory phenotype in a mouse model of Gulf War Illness is unrelated to brain regional levels of acetylcholine as measured by quantitative HILIC-UPLC-MS/MS.

PubMed

Miller, Julie V; LeBouf, Ryan F; Kelly, Kimberly A; Michalovicz, Lindsay T; Ranpara, Anand; Locker, Alicia R; Miller, Diane B; O'Callaghan, James P

2018-05-28

Many veterans of the 1991 Persian Gulf War (GW) returned with a chronic multisymptom illness that has been termed Gulf War Illness (GWI). Previous GWI studies have suggested that exposure to acetylcholinesterase inhibitors (AChEIs) in theater, such as sarin and/or pesticides, may have contributed to the symptomatology of GWI. Additionally, concomitant high physiological stress experienced during the war may have contributed to the initiation of the GWI phenotype. While inhibition of AChE leading to accumulation of acetylcholine (ACh) will activate the cholinergic anti-inflammatory pathway, the signature symptomatology of GWI has been shown to be associated with neuroinflammation. To investigate the relationship between ACh and neuroinflammation in discrete brain regions, we used our previously established mouse model of GWI, which combines an exposure to a high physiological stress mimic, corticosterone (CORT), with GW-relevant AChEIs. The AChEIs used in this study were diisopropyl fluorophosphate (DFP), chlorpyrifos oxon (CPO), and physostigmine (PHY). After AChEI exposure, ACh concentrations for cortex (CTX), hippocampus (HIP), and striatum (STR) were determined using hydrophilic interaction liquid chromatography (HILIC) with ultra-performance liquid chromatography (UPLC)-tandem-mass spectrometry (MS/MS). CORT pretreatment ameliorated the DFP-induced ACh increase in HIP and STR, but not CTX. CORT pretreatment did not significantly alter ACh levels for CPO and PHY. Further analysis of STR neuroinflammatory biomarkers revealed an exacerbated CORT+AChEI response, which does not correspond to measured brain ACh. By utilizing this new analytical method for discrete brain region analysis of ACh, this work suggests the exacerbated neuroinflammatory effects in our mouse model of GWI are not driven by the accumulation of brain region-specific ACh.

Biomarkers of animal health: integrating nutritional ecology, endocrine ecophysiology, ecoimmunology, and geospatial ecology.

PubMed

Warne, Robin W; Proudfoot, Glenn A; Crespi, Erica J

2015-02-01

Diverse biomarkers including stable isotope, hormonal, and ecoimmunological assays are powerful tools to assess animal condition. However, an integrative approach is necessary to provide the context essential to understanding how biomarkers reveal animal health in varied ecological conditions. A barrier to such integration is a general lack of awareness of how shared extraction methods from across fields can provide material from the same animal tissues for diverse biomarker assays. In addition, the use of shared methods for extracting differing tissue fractions can also provide biomarkers for how animal health varies across time. Specifically, no study has explicitly illustrated the depth and breadth of spacial and temporal information that can be derived from coupled biomarker assessments on two easily collected tissues: blood and feathers or hair. This study used integrated measures of glucocorticoids, stable isotopes, and parasite loads in the feathers and blood of fall-migrating Northern saw-whet owls (Aegolius acadicus) to illustrate the wealth of knowledge about animal health and ecology across both time and space. In feathers, we assayed deuterium (δD) isotope and corticosterone (CORT) profiles, while in blood we measured CORT and blood parasite levels. We found that while earlier migrating owls had elevated CORT levels relative to later migrating birds, there was also a disassociation between plasma and feather CORT, and blood parasite loads. These results demonstrate how these tissues integrate time periods from weeks to seasons and reflect energetic demands during differing life stages. Taken together, these findings illustrate the potential for integrating diverse biomarkers to assess interactions between environmental factors and animal health across varied time periods without the necessity of continually recapturing and tracking individuals. Combining biomarkers from diverse research fields into an integrated framework hold great promise for advancing our understanding of environmental effects on animal health.

Temporal dynamics of the HPA axis linked to exploratory behavior in a wild European songbird (Parus major).

PubMed

Baugh, Alexander T; Davidson, Sarah C; Hau, Michaela; van Oers, Kees

2017-09-01

Variation in the reactivity of the endocrine stress axis is thought to underlie aspects of persistent individual differences in behavior (i.e. animal personality). Previous studies, however, have focused largely on estimating baseline or peak levels of glucocorticoids (CORT), often in captive animals. In contrast, the temporal dynamics of the HPA axis-how quickly it turns on and off, for example-may better indicate how an individual copes with stressors. Moreover, these HPA components might be correlated, thereby representing endocrine suites. Using wild-caught great tits (Parus major) we tested birds for exploratory behavior using a standardized novel environment assay that serves as a validated proxy for personality. We then re-captured a subset of these birds (n=85) and characterized four components of HPA physiology: baseline, endogenous stress response, a dexamethasone (DEX) challenge to estimate the strength of negative feedback, and an adrenocorticotropic hormone (ACTH) challenge to estimate adrenal capacity. We predicted that these four HPA responses would be positively correlated and that less exploratory birds would have a more rapid onset of the stress response (a CORT elevation during the baseline bleed) and weaker negative feedback (higher CORT after DEX). We found support for the first two predictions but not the third. All four components were positively correlated with each other and less exploratory birds exhibited an elevation in CORT during the baseline bleed (<3min from capture). Less exploratory birds, however, did not exhibit weaker negative feedback following the DEX challenge, but did exhibit weaker adrenal capacity. Together, our findings provide partial support for the hypothesis that the temporal reactivity of the HPA axis is linked with consistent individual differences in behavior, with more cautious (slower exploring) individuals exhibiting a faster CORT response. Copyright © 2017 Elsevier Inc. All rights reserved.

Adolescent caffeine consumption increases adulthood anxiety-related behavior and modifies neuroendocrine signaling

PubMed Central

O’Neill, Casey E.; Newsom, Ryan J.; Stafford, Jacob; Scott, Talia; Archuleta, Solana; Levis, Sophia C.; Spencer, Robert L.; Campeau, Serge; Bachtell, Ryan K.

2016-01-01

Caffeine is a commonly used psychoactive substance and consumption by children and adolescents continues to rise. Here, we examine the lasting effects of adolescent caffeine consumption on anxiety-related behaviors and several neuroendocrine measures in adulthood. Adolescent male Sprague-Dawley rats consumed caffeine (0.3 g/L) for 28 consecutive days from postnatal day 28 (P28) to P55. Age-matched control rats consumed water. Behavioral testing for anxiety-related behavior began in adulthood (P62) 7 days after removal of caffeine. Adolescent caffeine consumption enhanced anxiety-related behavior in an open field, social interaction test, and elevated plus maze. Similar caffeine consumption in adult rats did not alter anxiety-related behavior after caffeine removal. Characterization of neuroendocrine measures was next assessed to determine whether the changes in anxiety were associated with modifications in the HPA axis. Blood plasma levels of corticosterone (CORT) were assessed throughout the caffeine consumption procedure in adolescent rats. Adolescent caffeine consumption elevated plasma CORT 24 h after initiation of caffeine consumption that normalized over the course of the 28-day consumption procedure. CORT levels were also elevated 24 h after caffeine removal and remained elevated for 7 days. Despite elevated basal CORT in adult rats that consumed caffeine during adolescence, the adrenocorticotropic hormone (ACTH) and CORT response to placement on an elevated pedestal (a mild stressor) was significantly blunted. Lastly, we assessed changes in basal and stress-induced c-fos and corticotropin-releasing factor (Crf) mRNA expression in brain tissue collected at 7 days withdrawal from adolescent caffeine. Adolescent caffeine consumption increased basal c-fos mRNA in the paraventricular nucleus of the hypothalamus. Adolescent caffeine consumption had no other effects on the basal or stress-induced c-fos mRNA changes. Caffeine consumption during adolescence increased basal Crf mRNA in the central nucleus of the amygdala, but no additional effects of stress or caffeine consumption were observed in other brain regions. Together these findings suggest that adolescent caffeine consumption may increase vulnerability to psychiatric disorders including anxiety-related disorders, and this vulnerability may result from dysregulation of the neuroendocrine stress response system. PMID:26874560

Predator stress-induced persistent emotional arousal is associated with alterations of plasma corticosterone and hippocampal steroid receptors in rat.

PubMed

Wang, Qingsong; Yu, Ke; Wang, Jun; Lin, Hang; Wu, Yuxian; Wang, Weiwen

2012-04-21

To investigate the long-term effects of psychological stress on emotionality, the emotional arousal of rats in 4 months after predator stress was assessed in both an open field environment and elevated plus maze. We also assessed the levels of plasma corticosterone (CORT) by radioimmunoassay, the distributions of brain glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) by immunohistochemistry, and the expressions of GR and MR by Western blot. The results showed that intense predator stress, which was adjusted to ensure consistent stressor intensity using rat tonic immobility behavior, successfully induced lasting decreased locomotor activity and habituation to novel environments, suppressed exploratory behavior, and increased anxiety-like behavior. The plasma CORT levels dramatically increased 1h after stress, then returned to basal levels at 1wk, decreased 1 month later, and remained significantly lower than control levels 4 months after exposure to stress. Immunohistochemical analysis showed that GR was markedly increased in the hippocampus and frontal cortexes of stressed rats and that the changes in the hippocampus were more pronounced. In contrast, MR expression was significantly decreased in both brain regions. Western analysis confirmed these dramatically elevated levels of GR expression and lower levels of MR expression in the hippocampus 4 months after stress. We conclude that acute severe psychological stress may induce long-term emotional behavioral changes, and that different patterns in plasma CORT, alterations in brain corticoid receptors, and increased hippocampal vulnerability to the effects of predator stress may play important roles in the persistent emotional arousal induced by intense psychological stress. Copyright © 2012 Elsevier B.V. All rights reserved.

Comprehensive growth performance, immune function, plasma biochemistry, gene expressions and cell death morphology responses to a daily corticosterone injection course in broiler chickens.

PubMed

Mehaisen, Gamal M K; Eshak, Mariam G; Elkaiaty, Ahmed M; Atta, Abdel-Rahman M M; Mashaly, Magdi M; Abass, Ahmed O

2017-01-01

The massive meat production of broiler chickens make them continuously exposed to potential stressors that stimulate releasing of stress-related hormones like corticosterone (CORT) which is responsible for specific pathways in biological mechanisms and physiological activities. Therefore, this research was conducted to evaluate a wide range of responses related to broiler performance, immune function, plasma biochemistry, related gene expressions and cell death morphology during and after a 7-day course of CORT injection. A total number of 200 one-day-old commercial Cobb broiler chicks were used in this study. From 21 to 28 d of age, broilers were randomly assigned to one of 2 groups with 5 replicates of 20 birds each; the first group received a daily intramuscular injection of 5 mg/kg BW corticosterone dissolved in 0.5 ml ethanol:saline solution (CORT group), while the second group received a daily intramuscular injection of 0.5 ml ethanol:saline only (CONT group). Growth performance, including body weight (BW), daily weight gain (DG), feed intake (FI) and feed conversion ratio (FC), were calculated at 0, 3 and 7 d after the start of the CORT injections. At the same times, blood samples were collected in each group for hematological (TWBC's and H/L ratio), T- and B-lymphocytes proliferation and plasma biochemical assays (total protein, TP; free triiodothyronine hormone, fT3; aspartate amino transaminase, AST; and alanine amino transaminase, ALT). The liver, thymus, bursa of Fabricius and spleen were dissected and weighed, and the mRNA expression of insulin-like growth factor 1 gene (IGF-1) in liver and cell-death-program gene (caspase-9) in bursa were analyzed for each group and time; while the apoptotic/necrotic cells were morphologically detected in the spleen. From 28 to 35 d of age, broilers were kept for recovery period without CORT injection and the same sampling and parameters were repeated at the end (at 14 d after initiation of the CORT injection). In general, all parameters of broiler performance were negatively affected by the CORT injection. In addition, CORT treatment decreased the plasma concentration of fT3 and the mRNA expression of hepatic IGF-1. A significant increase in liver weight accompanied by an increase in plasma TP, AST and ALT was observed with CORT treatment, indicating an incidence of liver malfunction by CORT. Moreover, the relative weights of thymus, bursa and spleen decreased by the CORT treatment with low counts of TWBC's and low stimulation of T & B cells while the H/L ratio increased; indicating immunosuppressive effect for CORT treatment. Furthermore, high expression of caspase-9 gene occurred in the bursa of CORT-treated chickens, however, it was associated with a high necrotic vs. low apoptotic cell death pathway in the spleen. Seven days after termination of the CORT treatment in broilers, most of these aspects remained negatively affected by CORT and did not recover to its normal status. The current study provides a comprehensive view of different physiological modulations in broiler chickens by CORT treatment and may set the potential means to mount a successful defense against stress in broilers and other animals as well.

Comprehensive growth performance, immune function, plasma biochemistry, gene expressions and cell death morphology responses to a daily corticosterone injection course in broiler chickens

PubMed Central

Atta, Abdel-Rahman M. M.; Mashaly, Magdi M.; Abass, Ahmed O.

2017-01-01

The massive meat production of broiler chickens make them continuously exposed to potential stressors that stimulate releasing of stress-related hormones like corticosterone (CORT) which is responsible for specific pathways in biological mechanisms and physiological activities. Therefore, this research was conducted to evaluate a wide range of responses related to broiler performance, immune function, plasma biochemistry, related gene expressions and cell death morphology during and after a 7-day course of CORT injection. A total number of 200 one-day-old commercial Cobb broiler chicks were used in this study. From 21 to 28 d of age, broilers were randomly assigned to one of 2 groups with 5 replicates of 20 birds each; the first group received a daily intramuscular injection of 5 mg/kg BW corticosterone dissolved in 0.5 ml ethanol:saline solution (CORT group), while the second group received a daily intramuscular injection of 0.5 ml ethanol:saline only (CONT group). Growth performance, including body weight (BW), daily weight gain (DG), feed intake (FI) and feed conversion ratio (FC), were calculated at 0, 3 and 7 d after the start of the CORT injections. At the same times, blood samples were collected in each group for hematological (TWBC’s and H/L ratio), T- and B-lymphocytes proliferation and plasma biochemical assays (total protein, TP; free triiodothyronine hormone, fT3; aspartate amino transaminase, AST; and alanine amino transaminase, ALT). The liver, thymus, bursa of Fabricius and spleen were dissected and weighed, and the mRNA expression of insulin-like growth factor 1 gene (IGF-1) in liver and cell-death-program gene (caspase-9) in bursa were analyzed for each group and time; while the apoptotic/necrotic cells were morphologically detected in the spleen. From 28 to 35 d of age, broilers were kept for recovery period without CORT injection and the same sampling and parameters were repeated at the end (at 14 d after initiation of the CORT injection). In general, all parameters of broiler performance were negatively affected by the CORT injection. In addition, CORT treatment decreased the plasma concentration of fT3 and the mRNA expression of hepatic IGF-1. A significant increase in liver weight accompanied by an increase in plasma TP, AST and ALT was observed with CORT treatment, indicating an incidence of liver malfunction by CORT. Moreover, the relative weights of thymus, bursa and spleen decreased by the CORT treatment with low counts of TWBC’s and low stimulation of T & B cells while the H/L ratio increased; indicating immunosuppressive effect for CORT treatment. Furthermore, high expression of caspase-9 gene occurred in the bursa of CORT-treated chickens, however, it was associated with a high necrotic vs. low apoptotic cell death pathway in the spleen. Seven days after termination of the CORT treatment in broilers, most of these aspects remained negatively affected by CORT and did not recover to its normal status. The current study provides a comprehensive view of different physiological modulations in broiler chickens by CORT treatment and may set the potential means to mount a successful defense against stress in broilers and other animals as well. PMID:28235061

Adrenalectomy amplifies aldosterone induced injury in cardiovascular tissue: an effect attenuated by adrenally derived steroids.

PubMed

Brem, Andrew S; Morris, David J; Li, Xiangpo; Ge, Yan; Shaw, Sunil; Gong, Rujun

2013-03-01

Aldosterone induces fibrotic changes in cardiovascular tissues but its effects have usually been demonstrated in models of pre-existing renal injury and/or hypertension. This study tests the hypothesis that aldosterone can directly induce vascular fibrotic changes in the absence of prior renal injury or hypertension. Experiments were conducted in intact or adrenalectomized (ADX) mice. Mice were divided into groups and treated for 1 week with vehicle or aldosterone (8 μg/kg/day)± inhibitor (800 μg/kg/day): CONTROLS, mice treated with aldosterone, ADX-CONTROLS, ADX+corticosterone (CORT 8 μg/kg/day), ADX with aldosterone, ADX with aldosterone plus the mineralocorticoid receptor (MR) antagonist RU-318, ADX with aldosterone+CORT (CORT inhibitor dose), and ADX with aldosterone+11-dehydro-CORT. Aortic smooth muscle to collagen ratio, aorta intimal thickness (μm), heart weight/body weight ratio (mg/gm), and left ventricular collagen (%) were measured. Prior to sacrifice, blood pressures were normal in all animals. Lower dose CORT alone had no effect on any of the variables examined. Aldosterone exposure was associated with extra-cellular matrix accumulation in cardiovascular tissues in intact mice and adrenalectomy exacerbated these effects. RU-318, CORT (inhibitor dose), and 11-deydro-CORT each attenuated the early fibrotic changes induced by aldosterone. In the heart, aldosterone exposure affected all the parameters measured and caused intimal hypercellularity with monocytes adhering to endothelial cells lining coronary vessels. Cultured endothelial cells exposed to aldosterone (10nM) released E-selectin, produced collagen, and promoted monocyte adhesion. These effects were inhibited by RU-318 and 11-deydro-CORT but not by CORT. Thus, adrenalectomy enhances aldosterone induced early fibrotic changes in heart and aorta. Aldosterone initially targets vascular endothelial cells. MR antagonists and 11-dehydro-CORT, an 11β-HSD dehydrogenase end-product, directly attenuate these effects. Copyright © 2012 Elsevier Inc. All rights reserved.

Prenatal betaine exposure alleviates corticosterone-induced inhibition of CYP27A1 expression in the liver of juvenile chickens associated with its promoter DNA methylation.

PubMed

Hu, Yun; Sun, Qinwei; Zong, Yibo; Liu, Jie; Idriss, Abdulrahman A; Omer, Nagmeldin A; Zhao, Ruqian

2017-05-15

Sterol 27-hydroxylase (CYP27A1) plays an important role in cholesterol homeostasis by degrading cholesterol to bile acids. Betaine can alleviate high-fat diet-induced hepatic cholesterol accumulation and maternal betaine treatment programs the hepatic expression of CYP27A1 in offspring. Excessive corticosterone (CORT) exposure causes hepatic cholesterol deposition in chickens, yet it remains unknown whether prenatal betaine modulates CORT-induced cholesterol accumulation in chicken liver later in life and whether it involves epigenetic gene regulation of CYP27A1. In this study, fertilized eggs were injected with saline or betaine at 2.5mg/egg before incubation, and the hatchlings were raised under the same condition till 56days of age followed by 7days of subcutaneous CORT injection. Plasma concentrations of total cholesterol (Tch), HDL- and LDL-cholesterol were significantly increased (P<0.05), after CORT challenge, in both control and betaine groups. However, prenatal betaine exposure prevented CORT-induced increase (P<0.05) in hepatic Tch content. Hepatic expression of cholesterol biosynthesis genes and ACAT1 protein that esterifies cholesterol for storage, were activated in both control and betaine groups upon CORT challenge. However, betaine-treated chickens were protected from CORT-induced repression (P<0.05) in LXR and CYP27A1 expression in the liver. CORT-induced down-regulation of LXR and CYP27A1 coincided with significantly increased (P<0.05) CpG methylation on their promoters, which was significantly ameliorated in betaine-treated chickens. These results suggest that in ovo betaine injection alleviates CORT-induced hepatic cholesterol deposition most probably through epigenetic regulation of CYP27A1 and LXR genes in juvenile chickens. Copyright © 2016 Elsevier Inc. All rights reserved.

Regulation of alternative splicing of Slo K+ channels in adrenal and pituitary during the stress-hyporesponsive period of rat development.

PubMed

Lai, Guey-Jen; McCobb, David P

2006-08-01

Stress triggers release of ACTH from the pituitary, glucocorticoids from the adrenal cortex, and epinephrine from the adrenal medulla. Although functions differ, these hormone systems interact in many ways. Previous evidence indicates that pituitary and steroid hormones regulate alternative splicing of the Slo gene at the stress axis-regulated exon (STREX), with functional implications for the calcium-activated K+ channels prominent in adrenal medullary and pituitary cells. Here we examine the role of corticosterone in Slo splicing regulation in pituitary and adrenal tissues during the stress-hyporesponsive period of early rat postnatal life. The sharp drop in plasma corticosterone (CORT) that defines this period offers a unique opportunity to test CORT's role in Slo splicing. We report that in both adrenal and pituitary tissues, the percentage of Slo transcripts having STREX declines and recovers in parallel with CORT. Moreover, addition of 500 nm CORT to cultures of anterior pituitary cells from 13-, 21-, and 30-d postnatal animals increased the percentage of Slo transcripts with STREX, whereas 20 microm CORT reduced STREX representation. Applied to adrenal chromaffin cells, 20 microm CORT decreased STREX inclusion, whereas neither 500 nm nor 2 microm had any effect. The mineralocorticoid receptor antagonist RU28318 abolished the effect of 500 nm CORT on splicing in pituitary cells, whereas the glucocorticoid receptor antagonist RU38486 blocked the effect of 20 microm CORT on adrenal chromaffin cells. These results support the hypothesis that the abrupt, transient drop in CORT during the stress-hyporesponsive period drives the transient decline in STREX splice variant representation in pituitary, but not adrenal.

Effect of corticosterone on larval growth, antipredator behaviour and metamorphosis of Hylarana indica.

PubMed

Kulkarni, P S; Gramapurohit, N P

2017-09-15

Corticosterone (CORT), a principal glucocorticoid in amphibians, is known to regulate diverse physiological processes including growth and metamorphosis of anuran tadpoles. Environmental stressors activate the neuroendocrine stress axis (hypothalamus-pituitary-interrenal axis, HPI) leading to an acute increase in CORT, which in turn, helps in coping with particular stress. However, chronic increase in CORT can negatively affect other physiological processes such as growth and metamorphosis. Herein, we studied the effect of exogenous CORT on larval growth, antipredator behaviour and metamorphic traits of Hylarana indica. Embryonic exposure to 5 or 20μg/L CORT did not affect their development, hatching duration as well as larval growth and metamorphosis. Exposure of tadpoles to 10 or 20μg/L CORT throughout larval development caused slower growth and development leading to increased body mass at stage 37. However, body and tail morphology of tadpoles was not affected. Interestingly, larval exposure to 5, 10 or 20μg/L CORT enhanced their antipredator response against kairomones in a concentration-dependent manner. Further, larval exposure to increasing concentrations of CORT resulted in the emergence of heavier froglets at 10 and 20μg/L while, delaying metamorphosis at all concentrations. Interestingly, the heavier froglets had shorter hindlimbs and consequently shorter jump distances. Tadpoles exposed to 20μg/L CORT during early, mid or late larval stages grew and developed slowly but tadpole morphology was not altered. Interestingly, exposure during early or mid-larval stages resulted in an enhanced antipredator response. These individuals metamorphosed later but at higher body mass while SVL was unaffected. Copyright © 2016 Elsevier Inc. All rights reserved.

Chronic stress alters concentrations of corticosterone receptors in a tissue-specific manner in wild house sparrows (Passer domesticus).

PubMed

Lattin, Christine R; Romero, L Michael

2014-07-15

The physiological stress response results in release of glucocorticoid hormones such as corticosterone (CORT). Whereas short-term activation of this response helps animals cope with environmental stressors, chronic activation can result in negative effects including metabolic dysregulation and reproductive failure. However, there is no consensus hormonal profile of a chronically stressed animal, suggesting that researchers may need to look beyond hormone titers to interpret the impacts of chronic stress. In this study, we brought wild house sparrows (Passer domesticus) into captivity. We then compared glucocorticoid and mineralocorticoid receptor concentrations in sparrows exposed either to a standardized chronic stress protocol (n=26) or to standard husbandry conditions (controls; n=20). We used radioligand binding assays to quantify receptors in whole brain, liver, kidneys, spleen, gonads, gastrocnemius and pectoralis muscle, omental and subcutaneous fat, and bib and back skin. In most tissues, CORT receptors did not differ between controls and stressed animals, although we found marginal increases in receptor density in kidney and testes in stressed birds at some time points. Only in pectoralis muscle was there a robust effect of chronic stress, with both receptor types higher in stressed animals. Increased pectoralis sensitivity to CORT with chronic stress may be part of the underlying mechanism for muscle wasting in animals administered exogenous CORT. Furthermore, the change in pectoralis was not paralleled by gastrocnemius receptors. This difference may help explain previous reports of a greater effect of CORT on pectoralis than on other muscle types, and indicate that birds use this muscle as a protein reserve. © 2014. Published by The Company of Biologists Ltd.

Effects of acute corticosterone treatment on partner preferences in male and female zebra finches (Taeniopygia guttata).

PubMed

LaPlante, Kimberly A; Huremovic, Enida; Tomaszycki, Michelle L

2014-04-01

Stress alters physiology and behavior across species. Most research on the effects of stress on behavior uses chronic stressors, and most are correlational. The effects of acute stressors on physiology and behavior have been mixed. Here, we use zebra finches, a highly gregarious species that forms long-term pair bonds, to test the effects of an acute corticosterone (CORT) on opposite-sex partner preferences over a same-sex individual or a group (the latter is a highly appealing option). We had two competing hypotheses. First, we predicted that acute CORT would alter preferences for the opposite sex bird in both conditions in both sexes. However, since there is a sex difference in the effects of CORT on partner preferences in voles, these effects may be more pronounced in males than in females. To test our hypotheses, we administered 2 doses of CORT (10μg and 20μg) or vehicle (control) using a repeated measures design. In the male vs. female test, there was a significant Sex by Treatment interaction, such that in males, 10μg CORT increased preferences for a female over the male compared to when these same males were treated with saline at baseline. There were no effects of treatment in females. In the opposite-sex vs. group condition, there was an overall effect of Treatment, such that the 10μg dose increased preference for the opposite-sex individual over both saline treatments, regardless of sex. These findings further our understanding of the effects of an acute stressor on sexual partner preferences. Copyright © 2014 Elsevier Inc. All rights reserved.

For the relief of Maria Eva Duran, Jessica Duran Cortes, Daniel Ivan Duran Cortes, and Jose Antonio Duran Cortes.

THOMAS, 111th Congress

Rep. Roybal-Allard, Lucille [D-CA-34

2010-09-20

House - 12/20/2010 Referred to the Subcommittee on Immigration, Citizenship, Refugees, Border Security, and International Law. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

Impacts of frequent, acute pulses of corticosterone on condition and behavior of Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii).

PubMed

Busch, D Shallin; Sperry, Todd S; Peterson, Eric; Do, Cam-Tu; Wingfield, John C; Boyd, Ellen H

2008-09-15

Little is known about how frequent, acute stressors affect wild animals. We present two experiments conducted on captive, Gambel's white-crowned sparrow (Zonotrichia leucophrys gambelii) that explore how frequent, acute doses of corticosterone (CORT) affect condition and behavior. CORT was administered either once or three times a day to birds in pre-breeding, early-breeding, or late-breeding life-history stages. Two additional groups were included to control for the CORT delivery vehicle, DMSO, and the treatment process. Our results indicate that CORT treatment decreases condition, but that its effects are dependent on frequency and life stage. Specifically, CORT-treated birds delayed the onset of molt and had reduced body mass, flight muscle, and food consumption. CORT treatment did not affect fat stores, bile retention in the gallbladder, or the expression of migratory restlessness behavior. These results increase our understanding of the effects of frequent, acute stressors and the development of chronic stress states.

Diurnal rhythms of the neuroendocrine system in professional riveters with different constitutional types.

PubMed

Gritsko, N; Shulga, V; Ivanova, L

1995-01-01

In our earlier investigations it have been shown that experimental vibration exposure causes different endocrine reactions in hypothalamo-pituitary-adrenocortical (HPA) and hypothalamo-pituitary-gonadal (HPG) systems in men of different constitutional types. The present study was carried out to determine diurnal rhythms of HPA and HPG systems in professional male riveters during a working day under industrial conditions. The state of HPA and HPG systems was evaluated according to the concentration of hormones cortisol (Cort.) and testosterone (T) in saliva. Mixed saliva was collected without stimulation at 7.00, 11.00, 15.00, 19.00 and 23.00 h. The concentration of hormones was determined by radio-immunoassay. Only healthy workers with a long working time under vibration exposure were chosen for participation in the investigation. The workers were divided into three groups of abdominal (A), muscular (M) and pectoral (P) somatotypes according to the antropometric signs (Bunaris classification, 1941). The results of investigating the HPA system have shown that usual diurnal rhythm of Cort, was observed in 60% of all cases. This rhythm is characterised by the maximum concentration of Cort, at 7.00 h with subsequent lowering during the day. In 10% of all cases we observed very low concentration of Cort, at 7.00 h and in 30% there was a significant increase of the level of Cort, at 15.00 and 19.00 h. Another change of diurnal rhythm was revealed in the HPG system. The diurnal rhythm of T completely corresponds to the rhythm of Cort. The accordance of T concentration to the diurnal rhythm we observed only in 27% of all cases. In 47% of all cases the increase of T took place at 15.00 and 19.00 h and in 20% the "monotonous" curve of T concentration without any changes of rhythm and with a low concentration at 7.00 h was observed. We also revealed different distribution of A, M and P somatotypes in connection with various diurnal rhythms of hormone curves. The result allows us to suppose that constitutional dependence of changes of diurnal rhythm of HPA and HPG systems probably underlines the adaptive processes to long time vibration exposure.

33 CFR 117.153 - Corte Madera Creek.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 33 Navigation and Navigable Waters 1 2011-07-01 2011-07-01 false Corte Madera Creek. 117.153 Section 117.153 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.153 Corte Madera Creek. The draw of...

33 CFR 117.153 - Corte Madera Creek.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 33 Navigation and Navigable Waters 1 2010-07-01 2010-07-01 false Corte Madera Creek. 117.153 Section 117.153 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY BRIDGES DRAWBRIDGE OPERATION REGULATIONS Specific Requirements California § 117.153 Corte Madera Creek. The draw of...

S 47445 Produces Antidepressant- and Anxiolytic-Like Effects through Neurogenesis Dependent and Independent Mechanisms

PubMed Central

Mendez-David, Indira; Guilloux, Jean-Philippe; Papp, Mariusz; Tritschler, Laurent; Mocaer, Elisabeth; Gardier, Alain M.; Bretin, Sylvie; David, Denis J.

2017-01-01

Glutamatergic dysfunctions are observed in the pathophysiology of depression. The glutamatergic synapse as well as the AMPA receptor’s (AMPAR) activation may represent new potential targets for therapeutic intervention in the context of major depressive disorders. S 47445 is a novel AMPARs positive allosteric modulator (AMPA-PAM) possessing procognitive, neurotrophic properties and enhancing synaptic plasticity. Here, we investigated the antidepressant/anxiolytic-like effects of S 47445 in a mouse model of anxiety/depression based on chronic corticosterone administration (CORT) and in the Chronic Mild Stress (CMS) model in rats. Four doses of S 47445 (0.3 to 10 mg/kg, oral route, 4 and 5 weeks, respectively) were assessed in both models. In mouse, behavioral effects were tested in various anxiety-and depression-related behaviors : the elevated plus maze (EPM), open field (OF), splash test (ST), forced swim test (FST), tail suspension test (TST), fur coat state and novelty suppressed feeding (NSF) as well as on hippocampal neurogenesis and dendritic arborization in comparison to chronic fluoxetine treatment (18 mg/kg, p.o.). In rats, behavioral effects of S 47445 were monitored using sucrose consumption and compared to those of imipramine or venlafaxine (10 mg/kg, i.p.) during the whole treatment period and after withdrawal of treatments. In a mouse model of genetic ablation of hippocampal neurogenesis (GFAP-Tk model), neurogenesis dependent/independent effects of chronic S 47445 treatment were tested, as well as BDNF hippocampal expression. S 47445 reversed CORT-induced depressive-like state by increasing grooming duration and reversing coat state’s deterioration. S 47445 also decreased the immobility duration in TST and FST. The highest doses (3 and 10 mg/kg) seem the most effective for antidepressant-like activity in CORT mice. Furthermore, S 47445 significantly reversed the anxiety phenotype observed in OF (at 1 mg/kg) and EPM (from 1 mg/kg). In the CMS rat model, S 47445 (from 1 mg/kg) demonstrated a rapid onset of effect on anhedonia compared to venlafaxine and imipramine. In the CORT model, S 47445 demonstrated significant neurogenic effects on proliferation, survival and maturation of hippocampal newborn neurons at doses inducing an antidepressant-like effect. It also corrected CORT-induced deficits of growth and arborization of dendrites. Finally, the antidepressant/anxiolytic-like activities of S 47445 required adult hippocampal neurogenesis in the novelty suppressed feeding test contrary to OF, EPM and ST. The observed increase in hippocampal BDNF levels could be one of the mechanisms of S 47445 responsible for the adult hippocampal neurogenesis increase. Altogether, S 47445 displays robust antidepressant-anxiolytic-like properties after chronic administration through neurogenesis dependent/independent mechanisms and neuroplastic activities. The AMPA-PAM S 47445 could have promising therapeutic potential for the treatment of major depressive disorders or generalized anxiety disorders. PMID:28769796

Agmatine attenuates chronic unpredictable mild stress-induced anxiety, depression-like behaviours and cognitive impairment by modulating nitrergic signalling pathway.

PubMed

Gawali, Nitin B; Bulani, Vipin D; Gursahani, Malvika S; Deshpande, Padmini S; Kothavade, Pankaj S; Juvekar, Archana R

2017-05-15

Agmatine, a neurotransmitter/neuromodulator, has shown to exert numerous effects on the CNS. Chronic stress is a risk factor for development of depression, anxiety and deterioration of cognitive performance. Compelling evidences indicate an involvement of nitric oxide (NO) pathway in these disorders. Hence, investigation of the beneficial effects of agmatine on chronic unpredictable mild stress (CUMS)-induced depression, anxiety and cognitive performance with the involvement of nitrergic pathway was undertaken. Mice were subjected to a battery of stressors for 28days. Agmatine (20 and 40mg/kg, i.p.) alone and in combination with NO modulators like L-NAME (15mg/kg, i.p.) and l-arginine (400mg/kg i.p.) were administered daily. The results showed that 4-weeks CUMS produces significant depression and anxiety-like behaviour. Stressed mice have also shown a significant high serum corticosterone (CORT) and low BDNF level. Chronic treatment with agmatine produced significant antidepressant-like behaviour in forced swim test (FST) and sucrose preference test, whereas, anxiolytic-like behaviour in elevated plus maze (EPM) and open field test (OFT) with improved cognitive impairment in Morris water maze (MWM). Furthermore, agmatine administration reduced the levels of acetylcholinesterase and oxidative stress markers. In addition, agmatine treatment significantly increased the BDNF level and inhibited serum CORT level in stressed mice. Treatment with L-NAME (15mg/kg) potentiated the effect of agmatine whereas l-arginine abolished the anxiolytic, antidepressant and neuroprotective effects of agmatine. Agmatine showed marked effect on depression and anxiety-like behaviour in mice through nitrergic pathway, which may be related to modulation of oxidative-nitrergic stress, CORT and BDNF levels. Copyright © 2017 Elsevier B.V. All rights reserved.

Dietary sodium manipulation during critical periods in development sensitize adult offspring to amphetamines

PubMed Central

McBride, Shawna M.; Culver, Bruce; Flynn, Francis W.

2008-01-01

This study examined critical periods in development to determine when offspring were most susceptible to dietary sodium manipulation leading to amphetamine sensitization. Wistar dams (n = 6–8/group) were fed chow containing low (0.12% NaCl; LN), normal (1% NaCl; NN), or high sodium (4% NaCl; HN) during the prenatal or early postnatal period (birth to 5 wk). Offspring were fed normal chow thereafter until testing at 6 mo. Body weight (BW), blood pressure (BP), fluid intake, salt preference, response to amphetamine, open field behavior, plasma adrenocorticotropin hormone (ACTH), plasma corticosterone (Cort), and adrenal gland weight were measured. BW was similar for all offspring. Offspring from the prenatal and postnatal HN group had increased BP, NaCl intake, and salt preference and decreased water intake relative to NN offspring. Prenatal HN offspring had greater BP than postnatal HN offspring. In response to amphetamine, both prenatal and postnatal LN and HN offspring had increased locomotor behavior compared with NN offspring. In a novel open field environment, locomotion was also increased in prenatal and postnatal LN and HN offspring compared with NN offspring. ACTH and Cort levels 30 min after restraint stress and adrenal gland weight measurement were greater in LN and HN offspring compared with NN offspring. These results indicate that early life experience with low- and high-sodium diets, during the prenatal or early postnatal period, is a stress that produces long-term changes in responsiveness to amphetamines and to subsequent stressors. PMID:18614766

Corticosterone primes the neuroinflammatory response to DFP in mice: potential animal model of Gulf War Illness.

PubMed

O'Callaghan, James P; Kelly, Kimberly A; Locker, Alicia R; Miller, Diane B; Lasley, Steve M

2015-06-01

Gulf War Illness (GWI) is a multi-symptom disorder with features characteristic of persistent sickness behavior. Among conditions encountered in the Gulf War (GW) theater were physiological stressors (e.g., heat/cold/physical activity/sleep deprivation), prophylactic treatment with the reversible AChE inhibitor, pyridostigmine bromide (PB), the insect repellent, N,N-diethyl-meta-toluamide (DEET), and potentially the nerve agent, sarin. Prior exposure to the anti-inflammatory glucocorticoid, corticosterone (CORT), at levels associated with high physiological stress, can paradoxically prime the CNS to produce a robust proinflammatory response to neurotoxicants and systemic inflammation; such neuroinflammatory effects can be associated with sickness behavior. Here, we examined whether CORT primed the CNS to mount neuroinflammatory responses to GW exposures as a potential model of GWI. Male C57BL/6 mice were treated with chronic (14 days) PB/ DEET, subchronic (7-14 days) CORT, and acute exposure (day 15) to diisopropyl fluorophosphate (DFP), a sarin surrogate and irreversible AChE inhibitor. DFP alone caused marked brain-wide neuroinflammation assessed by qPCR of tumor necrosis factor-α, IL6, chemokine (C-C motif) ligand 2, IL-1β, leukemia inhibitory factor, and oncostatin M. Pre-treatment with high physiological levels of CORT greatly augmented (up to 300-fold) the neuroinflammatory responses to DFP. Anti-inflammatory pre-treatment with minocycline suppressed many proinflammatory responses to CORT+DFP. Our findings are suggestive of a possible critical, yet unrecognized interaction between the stressor/environment of the GW theater and agent exposure(s) unique to this war. Such exposures may in fact prime the CNS to amplify future neuroinflammatory responses to pathogens, injury, or toxicity. Such occurrences could potentially result in the prolonged episodes of sickness behavior observed in GWI. Gulf War (GW) veterans were exposed to stressors, prophylactic medicines and, potentially, nerve agents in theater. Subsequent development of GW Illness, a persistent multi-symptom disorder with features characteristic of sickness behavior, may be caused by priming of the CNS resulting in exaggerated neuroinflammatory responses to pathogens/insults. Nerve agent, diisopropyl fluorophosphate (DFP), produced a neuroinflammatory response that was exacerbated by pre-treatment with levels of corticosterone simulating heightened stressor conditions. While prophylactic treatments reduced DFP-induced neuroinflammation, this effect was negated when those treatments were combined with corticosterone. © 2015 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of The International Society for Neurochemistry.

Preventive effects of zinc against psychological stress-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats.

PubMed

Li, Yingjie; Zheng, Yuanyuan; Qian, Jianxin; Chen, Xinmin; Shen, Zhilei; Tao, Liping; Li, Hongxia; Qin, Haihong; Li, Min; Shen, Hui

2012-06-01

Psychological stress (PS) could cause decreased iron absorption and iron redistribution in body resulting in low iron concentration in the bone marrow and inhibition of erythropoiesis. In the present study, we investigated the effect of zinc supplementation on the iron metabolism, erythropoiesis, and oxidative stress status in PS-induced rats. Thirty-two rats were divided into two groups randomly: control group and zinc supplementation group. Each group was subdivided into two subgroups: control group and PS group. Rats received zinc supplementation before PS exposure established by a communication box. We investigated the serum corticosterone (CORT) level; iron apparent absorption; iron contents in liver, spleen, cortex, hippocampus, striatum, and serum; hematological parameters; malondialdehyde (MDA); reduced glutathione (GSH); and superoxide dismutase (SOD). Compared to PS-treated rats with normal diet, the PS-treated rats with zinc supplementation showed increased iron apparent absorption, serum iron, hemoglobin, red blood cell, GSH, and SOD activities; while the serum CORT; iron contents in liver, spleen, and regional brain; and MDA decreased. These results indicated that dietary zinc supplementation had preventive effects against PS-induced iron dyshomeostasis, erythropoiesis inhibition, and oxidative stress status in rats.

Corticosterone-Induced Lipogenesis Activation and Lipophagy Inhibition in Chicken Liver Are Alleviated by Maternal Betaine Supplementation.

PubMed

Hu, Yun; Sun, Qinwei; Hu, Yan; Hou, Zhen; Zong, Yibo; Omer, Nagmeldin A; Abobaker, Halima; Zhao, Ruqian

2018-03-01

We have shown previously that in ovo betaine injection can prevent nonalcoholic fatty liver induced by glucocorticoid exposure in chickens; yet it remains unknown whether feeding betaine to laying hens may exert similar effects in their progeny. In this study, we fed laying hens a betaine-supplemented diet, and the progeny were later exposed chronically to corticosterone (CORT) to test hepatoprotective effects and further elucidate underlying mechanisms. Rugao yellow-feathered laying hens (n = 120) were fed a basal (control, C) diet or a 0.5% betaine-supplemented (B) diet for 28 d before their eggs were collected for incubation. At 49 d of age, male chickens selected from each group were daily injected subcutaneously with solvent (15% ethanol; vehicle, VEH) or CORT (4.0 mg/kg body mass) for 7 d to establish a fatty liver model. Chickens in the 4 groups (C-VEH, C-CORT, B-VEH, and B-CORT) were killed at day 57. Plasma and hepatic triglyceride (TG) concentrations, as well as the hepatic expression of genes involved in lipogenesis and lipophagy, were determined. CORT induced a 1.6-fold increase in the plasma TG concentration (P < 0.05) and a 1.8-fold increment in the hepatic TG concentration (P < 0.05), associated with activation of lipogenic genes (70-780%). In contrast, lipophagy and mitochondrial β-oxidation genes were inhibited by 30-60% (P < 0.05) in CORT-treated chickens. These CORT-induced changes were completely normalized by maternal betaine supplementation or were partially normalized to intermediate values that were significantly different from those in the C-VEH and C-CORT groups. These effects were accompanied by modifications in CpG methylation and glucocorticoid receptor binding to the promoters of major lipogenic and lipophagic genes (P < 0.05). These results indicate that maternal betaine supplementation protects male juvenile chickens from CORT-induced TG accumulation in the liver via epigenetic modulation of lipogenic and lipophagic genes.

Neuroprotective evidence of alpha-lipoic acid and desvenlafaxine on memory deficit in a neuroendocrine model of depression.

PubMed

de Sousa, Caren Nádia Soares; Meneses, Lucas Nascimento; Vasconcelos, Germana Silva; da Silva Medeiros, Ingridy; Silva, Márcia Calheiros Chaves; Mouaffak, Fayçal; Kebir, Oussama; da Silva Leite, Cláudio Manuel Gonçalves; Patrocinio, Manoel Cláudio Azevedo; Macedo, Danielle; Vasconcelos, Silvânia Maria Mendes

2018-05-07

Cognitive impairment is present in patients with depression. We hypothesized that alpha-lipoic acid (ALA) can reduce cognitive impairment, especially when combined to antidepressants. Female mice received vehicle or corticosterone (CORT) 20 mg/kg, s.c. for 14 days. From the 15th to 21st day, the animals were divided in groups: vehicle, CORT, CORT+desvenlafaxine (DVS) 10 or 20 mg/kg, ALA 100 or 200 mg/kg, DVS10+ALA100, DVS20+ALA100, DVS10+ALA200, or DVS20+ALA200. Tail suspension (TST), social interaction (SIT), novel object recognition (NOR), and Y-maze tests were conducted. Acetylcholinesterase activity (AChE) was measured in the prefrontal cortex (PFC), hippocampus (HC), and striatum (ST). CORT caused depressive-like behavior, impairment in SIT, and cognitive deficits. Alpha-lipoic acid and DVS, alone or combined, reversed CORT effect on TST. In the NOR, ALA200 alone, DVS10+ALA100, or DVS10+ALA200 reversed the deficits in short-term memory, while DVS20 alone or DVS20+ALA200 reversed the deficits in long-term memory. In the Y-maze test, ALA200 alone, DVS20+ALA100, or DVS20+ALA200 reversed the deficits caused by CORT in the working memory. CORT increased AChE in the PFC, HC, and ST. ALA200 alone or DVS20+ALA200 reversed this effect in the PFC, while DVS20 or DVS20+ALA100 reversed this effect in the HC. In the ST, DVS10 or 20, alone or combined, and ALA100 reversed the effects of CORT. These results suggest that DVS+ALA, by reversing CORT-induced memory and social deficits, seems to be a promising therapy for the treatment of depression and reversal of cognitive impairment observed in this disorder.

Elevated paternal glucocorticoid exposure modifies memory retention in female offspring.

PubMed

Yeshurun, Shlomo; Rogers, Jake; Short, Annabel K; Renoir, Thibault; Pang, Terence Y; Hannan, Anthony J

2017-09-01

Recent studies have demonstrated that behavioral traits are subject to transgenerational modification by paternal environmental factors. We previously reported on the transgenerational influences of increased paternal stress hormone levels on offspring anxiety and depression-related behaviors. Here, we investigated whether offspring sociability and cognition are also influenced by paternal stress. Adult C57BL/6J male mice were treated with corticosterone (CORT; 25mg/L) for four weeks prior to paired-matings to generate F1 offspring. Paternal CORT treatment was associated with decreased body weights of female offspring and a marked reduction of the male offspring. There were no differences in social behavior of adult F1 offspring in the three-chamber social interaction test. Despite male offspring of CORT-treated fathers displaying hyperactivity in the Y-maze, there was no observable difference in short-term spatial working memory. Spatial learning and memory testing in the Morris water maze revealed that female, but not male, F1 offspring of CORT-treated fathers had impaired memory retention. We used our recently developed methodology to analyze the spatial search strategy of the mice during the learning trials and determined that the impairment could not be attributed to underlying differences in search strategy. These results provide evidence for the impact of paternal corticosterone administration on offspring cognition and complement the cumulative knowledge of transgenerational epigenetic inheritance of acquired traits in rodents and humans. Copyright © 2017 Elsevier Ltd. All rights reserved.

In ovo injection of betaine alleviates corticosterone-induced fatty liver in chickens through epigenetic modifications

PubMed Central

Hu, Yun; Sun, Qinwei; Liu, Jie; Jia, Yimin; Cai, Demin; Idriss, Abdulrahman A.; Omer, Nagmeldin A.; Zhao, Ruqian

2017-01-01

Betaine alleviates high-fat diet-induced fatty liver and prenatal betaine programs offspring hepatic lipid metabolism. Excessive corticosterone (CORT) exposure causes fatty liver in chickens, yet it remains unknown whether and how prenatal betaine modulates the susceptibility of CORT-induced fatty liver later in life. In this study, fertilized eggs were injected with saline or betaine before incubation, and the hatchlings were raised at 8 weeks of age followed by 7 days of subcutaneous CORT injection. CORT-induced fatty liver was less severe in betaine-treated chickens, with significantly reduced oil-red staining and hepatic triglyceride content (P < 0.05). The protective effect of prenatal betaine was associated with significantly up-regulated expression of PPARα and CPT1α, as well as mitochondrial DNA (mtDNA)-encoded genes (P < 0.05). Moreover, betaine rescued CORT-induced alterations in methionine cycle genes, which coincided with modifications of CpG methylation on CPT1α gene promoter and mtDNA D-loop regions. Furthermore, the elevation of hepatic GR protein content after CORT treatment was significantly reduced (P < 0.05), while the reduction of GR binding to the control region of affected genes was significantly increased (P < 0.05), in betaine-treated chickens. These results indicate that in ovo betaine injection protects the juvenile chickens from CORT-induced fatty liver. PMID:28059170

Immune responses of eastern fence lizards (Sceloporus undulatus) to repeated acute elevation of corticosterone.

PubMed

McCormick, Gail L; Langkilde, Tracy

2014-08-01

Prolonged elevations of glucocorticoids due to long-duration (chronic) stress can suppress immune function. It is unclear, however, how natural stressors that result in repeated short-duration (acute) stress, such as frequent agonistic social encounters or predator attacks, fit into our current understanding of the immune consequences of stress. Since these types of stressors may activate the immune system due to increased risk of injury, immune suppression may be reduced at sites where individuals are repeatedly exposed to potentially damaging stressors. We tested whether repeated acute elevation of corticosterone (CORT, a glucocorticoid) suppresses immune function in eastern fence lizards (Sceloporus undulatus), and whether this effect varies between lizards from high-stress (high baseline CORT, invaded by predatory fire ants) and low-stress (low baseline CORT, uninvaded) sites. Lizards treated daily with exogenous CORT showed higher hemagglutination of novel proteins by their plasma (a test of constitutive humoral immunity) than control lizards, a pattern that was consistent across sites. There was no significant effect of CORT treatment on bacterial killing ability of plasma. These results suggest that repeated elevations of CORT, which are common in nature, produce immune effects more typical of those expected at the acute end of the acute-chronic spectrum and provide no evidence of modulated consequences of elevated CORT in animals from high-stress sites. Copyright © 2014 Elsevier Inc. All rights reserved.

Rare Social Marketing for Sustainable Fishing in Cortes, Surigao Del Sur, Philippines

ERIC Educational Resources Information Center

Day, Brian A.; DeWan, Amielle; Cadiz, Fel Ceasar; Jakosalem-Balane, Joy; Dueñas, Vincent; Trinidad, Pedro M., Jr.

2014-01-01

Rare's approach to promoting sustainable fishing through social marketing in the Philippines is exemplified in the Cortes Pride campaign. The Cortes Pride campaign is a social marketing behavior change program that was part of a cohort of 12 similar sustainable fishing campaigns in the Philippines, all of which used a unique blend of social…

Impact of PACAP and PAC1 receptor deficiency on the neurochemical and behavioral effects of acute and chronic restraint stress in male C57BL/6 mice.

PubMed

Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E

2015-01-01

Acute restraint stress (ARS) for 3 h causes corticosterone (CORT) elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following 7-day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1-deficient mice. However, longer periods of daily restraint (14-21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of ARS and short-term (<7 days) CRS on the hypothalamo-pituitary-adrenal (HPA) axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) CRS.

Impact of physical fitness on salivary stress markers in sedentary to low-active young to middle-aged men.

PubMed

Strahler, Jana; Fuchs, Reinhard; Nater, Urs M; Klaperski, Sandra

2016-06-01

Salivary cortisol (sCort) and alpha-amylase (sAA) are popular measurement tools for investigating hypothalamic-pituitary-adrenal and autonomic functioning, respectively. Despite their widespread use, only little is known about whether lifestyle factors such as regular exercise and physical fitness impact these two salivary stress markers. The lack of an objectively assessed fitness status is a major drawback of nearly all previous studies in this area. Our main objective was therefore to examine the impact of fitness status on sCort and sAA responses to a validated stressor. Sedentary to low-active men (N=115, 45.7±10.1 years, 26.7±3.4kg/m(2)) were exposed to the Trier Social Stress Test for Groups and provided saliva samples before and repeatedly after the stressor. An ergometer lactate exercise test provided information on physical fitness, that is, power achieved at the individual anaerobic threshold relative to body weight. From age-specific percentiles, a 2- (n=65 low fitness, n=50 high fitness) and a 3-group (n=37 low fitness, n=49 moderate fitness, n=29 high fitness) solution were calculated to elucidate the impact of different fitness levels. Prior to stress testing, sCort and sAA levels were similar in all groups. While both markers increased significantly due to stress exposure, fitness effects appeared rather small. When applying the 3-group solution, we observed attenuated sCort slopes in high- and moderate-fit men. Although sAA response slopes were pronounced in high-fit men, they failed to reach statistical significance. Mean stress reactivity (area under the curve with respect to ground, baseline, and response maximum) did not differ between groups and no association with fitness level was found. Our findings suggest only a weak effect of objectively assessed physical fitness on biological stress responses with attenuated hypothalamic-pituitary-adrenal but (non-significantly) higher autonomic responses in fitter men. Physical fitness is a factor that should not be neglected in future studies employing salivary stress markers, especially in studies interested in acute stress responses. Copyright © 2016 Elsevier Ltd. All rights reserved.

Suppressed osteoclast differentiation at the chondro-osseous junction mediates endochondral ossification retardation in long bones of Wistar fetal rats with prenatal ethanol exposure

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pan, Zhengqi

Prenatal ethanol exposure (PEE) inhibits longitudinal growth of fetal bones, but the underlying mechanisms remain unknown. In this study, we aimed to investigate how PEE induces the retardation of long bone development in fetal rats. Pregnant Wistar rats were treated with ethanol or distilled water (control group) by gavage from gestational day (GD) 9 to 20. Fetuses were delivered by cesarean section on GD20. Fetal sera were collected for assessing corticosterone (CORT) level. Fetal long bones were harvested for histochemical, immunohistochemical and gene expression analysis. Primary chondrocytes were treated with ethanol or CORT for analyzing genes expression. PEE fetuses showedmore » a significant reduction in birth weight and body length. The serum CORT concentration in PEE group was significantly increased, while the body weight, body length and femur length all were significantly decreased in the PEE group. The length of the epiphyseal hypertrophy zone was enlarged, whereas the length of the primary ossification center was significantly reduced in PEE fetuses. TUNEL assay showed reduced apoptosis in the PEE group. Further, the gene expression of osteoprotegerin (OPG) was markedly up-regulated. In vitro experiments showed that CORT (but not ethanol) treatment significantly activated the expression of OPG, while the application of glucocorticoid receptor inhibitor, mifepristone, attenuated these change induced by CORT. These results indicated that PEE-induced glucocorticoid over-exposure enhanced the expression of OPG in fetal epiphyseal cartilage and further lead to the suppressed osteoclast differentiation in the chondro-osseous junction and consequently inhibited the endochondral ossification in long bones of fetal rats. - Highlights: • Glucocorticoid but not ethanol enhanced the expression of OPG in chondrocytes. • PEE reduced osteoclast differentiation relative with over-expression of OPG. • PEE inhibited endochondral ossification in fetal long bones of rats. • Endochondral ossification delay is regarded as the thrifty phenotype induced by PEE.« less

Ferulic acid reverses depression-like behavior and oxidative stress induced by chronic corticosterone treatment in mice.

PubMed

Zeni, Ana Lúcia Bertarello; Camargo, Anderson; Dalmagro, Ana Paula

2017-09-01

Corticosterone (CORT) treatment has been evidenced to develop a depression-like state in animals, that mimic hypothalamic-pituitary-adrenal (HPA)-axis dysregulation implicated in the development of depression. The present study aimed to examine the ferulic acid (FA), a natural phenolic compound, antidepressant and antioxidant activities on the CORT chronic model. Mice orally treated with 20mg/kg of CORT for 21days were connsidered control group, while mice treated with FA (1mg/kg) or fluoxetine (10mg/kg) for the last week of CORT treatment, as drug groups. Three weeks of CORT treatment resulted in depressive-like behavior, as indicated by the increase on the immobility time in the tail suspension test, grooming in the splash test and an increase in the oxidative stress markers in the brain. It was observed that FA ameliorated the behavioral and oxidative stress alterations induced by CORT, which may plausibly suggest a mode of action for the FA antidepressant effect. The involvement of FA repairing the stress caused by HPA-axis dysfunction evidenced that this phenolic acid could be further investigated as a novel potential agent to improve the management of depression. Copyright © 2017 Elsevier Inc. All rights reserved.

Programming effects of antenatal corticosteroids exposure in male sexual behavior.

PubMed

Oliveira, Mário; Leão, Pedro; Rodrigues, Ana-João; Pêgo, José-Miguel; Cerqueira, João-José; Sousa, Nuno

2011-07-01

Brain regions implicated in sexual behavior begin to differentiate in the last trimester of gestation. Antenatal therapy with corticosteroids is often used in clinical practice during this period to accelerate lung maturation in preterm-risk pregnancies. Clinical and animal studies highlighted major behavioral impairments induced later in life by these treatments, especially when synthetic corticosteroids are used. To evaluate the implications of acute prenatal treatment with natural vs. synthetic corticosteroids on adult male rat sexual behavior and its neurochemical correlates. Twelve pregnant Wistar rats were injected with dexamethasone (DEX-1 mg/kg), corticosterone (CORT-25 mg/kg), or saline on late gestation (pregnancy days 18 and 19). Following this brief exposure to corticosteroids, we assessed the sexual behavior of the adult male progeny and subsequently associated these behaviors with the levels of catecholamines and mRNA of dopamine and androgen receptors (AR) in brain regions relevant for sexual behavior. Sexual behavior of adult male offspring was assessed by exposure to receptive females. This was associated with serum testosterone levels and levels of catecholamines (determined by high-performance liquid chromatography) and dopamine and AR mRNA expression (real-time polymerase chain reaction [PCR]) in brain regions implicated in sexual behavior. Prenatal DEX exposure resulted in a decreased number and increased mounts and intromissions latencies in adulthood. These findings were associated with decreased levels of serum testosterone and increased hypothalamic expression of AR mRNA. DEX animals also displayed lower dopamine levels and higher dopamine receptor mRNA expression both in hypothalamus and nucleus accumbens (NAcc). The milder phenotype of CORT animals was associated only with decreased dopamine levels in NAcc. Antenatal corticotherapy programs adult male sexual behavior through changes in specific neuronal and endocrine mediators. Importantly, equipotent doses of CORT trigger less detrimental consequences than DEX, emphasizing the differential impact of activation of the different corticosteroid receptors. © 2011 International Society for Sexual Medicine.

Hernan Cortes; Conquistador and Colonizer. The Tinker Pamphlet Series for the Teaching of Mexican American Heritage.

ERIC Educational Resources Information Center

Miller, Hubert J.

The conquest and colonization of Mexico initiated by Hernan Cortes resulted in the fusion of the Indian and Hispanic cultures. This fusion led to the "mestizo" culture. Cortes was the bearer of the Hispanic heritage just as the Aztecs and other Indians in Mexico and the Southwest were the carriers of the Indian heritage. In studying the…

[Effect of AÇaí (Euterpe oleracea) on lipid metabolism, immune substances and endocrine hormone in rats with deficiency-heat and deficiency-cold syndrome].

PubMed

Wang, Zi-Chen; Zhang, Jian-Jun; Zhu, Ying-Li; Qu, Yan; Fei, Wen-Ting; Wang, Sha; Wang, Jing-Xia; Wang, Lin-Yuan

2017-07-01

To study the effects of AÇaí(Euterpe oleracea) on lipid metabolism, immune substances and endocrine hormone level in rats with deficiency-heat and deficiency-cold syndrome. SD rats were divided into blank control group, deficiency-heat model group, deficiency-heat & Phellodendri Cortex group, deficiency-heat & AÇaí high dose and low dose groups, deficiency-cold model group, deficiency-cold & Cinnamomi Cortex group, deficiency-cold & AÇaí high dose and low dose groups. The rats received intramuscular injection of dexamethasone sodium phosphate (0.35 mg) or hydrocortisone sodium succinate (20 mg) for 21 days to set up deficiency-heat models and deficiency-cold models. Then the changes in fatmetabolism levels (FFA, LPL, HL) and immune indexes (IgG, IgM, C3 and C4) were detected by colorimeter; and the levels of endocrine hormone indexes (CORT, E2 and T) were detected by radioimmunoassay. The levels of FFA, LPL and HL in serum were reduced (P<0.01 or P<0.001); levels of IgG, IgM and C3 in serum were increased (P<0.05 or P<0.001); level of CORT in serum was increased (P<0.05) and the level of E2, E2/T in serum were reduced in the AÇaí high dose group (P<0.05). The effect of high dose AÇaí on fat metabolism was not obvious in deficiency-cold models, but the levels of IgG, IgM, C3 and CORT in serum were increased (P<0.05 or P<0.001). AÇaí was showed the same effect trend with Phellodendri Cortex in adjusting the levels of deficiency-heat rats; but unlike Cinnamomi Cortex, AÇaí was showed no obvious effect in adjusting the levels of deficiency-cold rats. In this experiment, homogeneous comparison and heterogeneous disproof were used to verify the cold nature of Çaí. Copyright© by the Chinese Pharmaceutical Association.

Development of Alopecia Areata Is Associated with Higher Central and Peripheral Hypothalamic–Pituitary–Adrenal Tone in the Skin Graft Induced C3H/HeJ Mouse Model

PubMed Central

Zhang, Xingqi; Yu, Mei; Yu, Wayne; Weinberg, Joanne; Shapiro, Jerry; McElwee, Kevin J.

2016-01-01

The relationship of the stress response to the pathogenesis of alopecia areata (AA) was investigated by subjecting normal and skin graft-induced, AA-affected C3H/HeJ mice to light ether anesthesia or restraint stress. Plasma corticosterone (CORT), adrenocorticotropic hormone (ACTH), and estradiol (E2) levels were determined by RIA, whereas gene expression in brains, lymphoid organs, and skin was measured by quantitative RT-PCR for corticotropin-releasing hormone (Crh), arginine vasopressin (Avp), proopiomelanocortin (Pomc), glucocorticoid receptor (Nr3c1), mineralo corticoid receptor (Nr3c2), corticotropin-releasing hormone receptor types 1 and 2 (Crhr1, Crhr2), interleukin-12 (Il12), tumor necrosis factor-α (Tnfα), and estrogen receptors type-1 (Esr1) and type-2 (Esr2). AA mice had a marked increase in hypothalamic–pituitary–adrenal (HPA) tone and activity centrally, and peripherally in the skin and lymph nodes. There was also altered interaction between the adrenal and gonadal axes compared with that in normal mice. Stress further exacerbated changes in AA mouse HPA activity both centrally and peripherally. AA mice had significantly blunted CORT and ACTH responses to acute ether stress (physiological stressor) and a deficit in habituation to repeated restraint stress (psychological stressor). The positive correlation of HPA hormone levels with skin Th1 cytokines suggests that altered HPA activity may occur as a consequence of the immune response associated with AA. PMID:19020552

Snow cover and snowfall impact corticosterone and immunoglobulin a levels in a threatened steppe bird.

PubMed

Liu, Gang; Hu, Xiaolong; Kessler, Aimee Elizabeth; Gong, Minghao; Wang, Yihua; Li, Huixin; Dong, Yuqiu; Yang, Yuhui; Li, Linhai

2018-05-15

Birds use both the corticosterone stress response and immune system to meet physiological challenges during exposure to adverse climatic conditions. To assess the stress level and immune response of the Asian Great Bustard during conditions of severe winter weather, we measured fecal corticosterone (CORT) and Immunoglobulin A (IgA) before and after snowfall in a low snow cover year (2014) and a high snow cover year (2015). A total of 239 fecal samples were gathered from individuals in Tumuji Nature Reserve, located in eastern Inner Mongolia, China. We observed high CORT levels that rose further after snowfall both in high and low snow cover years. IgA levels increased significantly after snowfall in the low snow cover year, but decreased after snowfall in the high snow cover year. These results suggest that overwintering Asian Great Bustards are subjected to climatic stress during severe winter weather, and the hypothalamic-pituitary-adrenal axis and immune system react to this challenge. Extreme levels of stress, such as snowfall in already prolonged and high snow cover conditions may decrease immune function. Supplemental feeding should be considered under severe winter weather conditions for this endangered subspecies. Copyright © 2018 Elsevier Inc. All rights reserved.

Measurement of steroids in rats after exposure to an endocrine disruptor: mass spectrometry and radioimmunoassay demonstrate similar results.

PubMed

Riffle, Brandy W; Henderson, W Matthew; Laws, Susan C

2013-01-01

Commercially available radioimmunoassays (RIAs) are frequently used to evaluate the effects of endocrine disrupting chemicals (EDCs) on steroidogenesis in rats. Currently there are limited data comparing steroid concentrations in rats as measured by RIAs to those obtained using liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). This study evaluates the concordance of serum and urine steroid concentrations as quantified by select RIA kits and LC-MS/MS following exposure to an EDC, atrazine (ATR). Adult male rats were orally dosed with ATR (200 mg/kg/day) or methylcellulose (1%, vehicle control) for 5 days. Serum was collected and separated into aliquots for analysis. Serum was assayed by RIA for androstenedione (ANDRO), corticosterone (CORT), estradiol (E2), estrone (E1), progesterone (P4), and testosterone (T). Serum was extracted prior to LC-MS/MS analysis with positive electrospray ionization in multiple-reaction monitoring mode for ANDRO, CORT, P4, and T. E1 and E2 concentrations were quantified similarly by LC-MS/MS, following derivatization with dansyl chloride. To compare CORT values from urine, pregnant adult rats were orally dosed with either ATR (100 mg/kg/day) or methylcellulose for 5 days (i.e., gestational days 14-18). Urine samples were collected daily and assayed for CORT by RIA and LC-MS/MS as described above. Data analyses demonstrated significant agreement between the two detection methods as assessed by Pearson product-moment correlation coefficient, Bland-Altman analysis, and the interclass correlation coefficient. No statistically significant differences were observed between RIA and LC-MS/MS means for any of the steroids assayed. These findings indicate a significant correlation between the measurement of steroids within rat serum and urine using RIA kits and LC-MS/MS. Differences in the absolute measurements existed, but these were not statistically significant. These findings indicate that steroids may be reliably measured in rat biological media using RIAs or LC-MS/MS. © 2013.

Julio Cortázar quotes on normal and abnormal movements: magical realism or reality?

PubMed

Merello, Marcelo

2006-08-01

Together with Mario Vargas Llosa and Gabriel García Márquez, Julio Cortázar was one of the most representative authors of the Latin American magical realism genre. Within his extensive body of work, many descriptions of characters suffering physical disabilities, as well as situations suggesting such medical conditions, can be extracted. In this review, two short stories by Cortázar are presented. In the first one, the main character could easily be a man suffering from corticobasal degeneration; in the second, an old woman with symptoms suggestive of progressive supranuclear palsy is clearly depicted. Despite the fact that one of the main ingredients in Cortázar's magical realism is fiction, cases described here fit real medical conditions quite well, making it hard to believe that they represent purely fantastic descriptions rather than the product of Cortázar's inquisitive observation and the description of real patients. (c) 2006 Movement Disorder Society

Mindfulness training attenuates the increase in salivary cortisol concentration associated with competition in highly trained wheelchair-basketball players.

PubMed

MacDonald, Luke A; Minahan, Clare L

2018-02-01

This study determined the effect of 8 wk of mindfulness training (MT) on salivary cortisol (sCort) and rate of salivary Immunoglobulin-A (sIgA) secretion in wheelchair-basketball players during a competition period. The mindful group completed 8 weeks of MT in addition to training and competition. sCort and rate of sIgA secretion were measured at baseline, at 2-week intervals, the end and 2 weeks following the intervention. A significant time and group interaction was observed for sCort (F = 3.297, P = 0.040, ES = 0.191); sCort increased in the control group from MT-BL to MT-2wk (P = 0.001) and remained significantly elevated at MT-4wk (P = 0.013) and MT-6wk (P = 0.002). sCort decreased from MT-6wk to MT-8wk (P < 0.001) and concentrations were not different at MT-8wk and Post-2wk to MT-BL (P > 0.05). Mindful group sCort increased from MT-BL to MT-2wk (P = 0.042) but decreased to concentrations no different to MT-BL for the rest of the intervention period (P > 0.05). There were no group differences in rate of sIgA secretion during the intervention (P = 0.810). It was concluded that 8 weeks of MT attenuated the increase in sCort associated with the competition period.

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

PubMed

Grace, Jacquelyn K; Anderson, David J

2014-11-01

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. Copyright © 2014 Elsevier Inc. All rights reserved.

Corticotrophin-releasing hormone and corticosterone impair development of preimplantation embryos by inducing oviductal cell apoptosis via activating the Fas system: an in vitro study.

PubMed

Tan, Xiu-Wen; Ji, Chang-Li; Zheng, Liang-Liang; Zhang, Jie; Yuan, Hong-Jie; Gong, Shuai; Zhu, Jiang; Tan, Jing-He

2017-08-01

What are the mechanisms by which corticotrophin-releasing hormone (CRH) and corticosterone impair the development of preimplantation embryos in the oviduct. CRH and corticosterone do not affect preimplantation embryos directly, but impair their development indirectly by triggering apoptosis of oviductal epithelial cells (OECs) through activation of the Fas system. Studies report that stress impairs embryo development with facilitated secretion of CRH and glucocorticoids. Although an in vivo study demonstrated that preimplantation stress impaired embryo development in conjunction with oviductal apoptosis and activation of the Fas system, whether CRH or glucocorticoids damage embryos directly or indirectly by way of oviductal cells remains to be clarified. Mice of Kunming strain, the generalized lymphoproliferative disorder (gld) mice with a germline mutation F273L in Fas ligand in a C57BL/6J genomic background and the wild-type C57BL/6J mice were used. Female mice were used 8-10 weeks after birth. While some female mice were killed 48 h after being injected with equine CG to collect oviducts and prepare OECs, others were killed to recover zygotes after mating with males following superovulation with eCG and hCG. The zygotes obtained were cultured with or without CRH or corticosterone (CRH/Cort) either in Chatot-Ziomek-Bavister (CZB) medium with or without OECs or in conditioned medium (CM) conditioned with OECs pretreated or not with CRH/Cort. Preimplantation development, levels of redox potential and apoptosis, and expression of CRH receptor 1 (CRHR1), glucocorticoid receptor (GR), Fas and 11β-hydroxysteroid dehydrogenase (HSD) were observed in embryos recovered at different times of in vitro culture. After culture of OECs with or without CRH/Cort, levels of redox potential and apoptosis, mRNA and protein expression of growth factors, and protein expression of CRHR1, GR and Fas were examined in OECs and the level of FasL was measured in CM. The gld mice were used to confirm a role for the Fas system in triggering apoptosis of embryos and oviducts. This study showed that blastocyst development was unaffected when mouse zygotes were cultured in CZB medium containing various concentrations of CRH/Cort but was impaired when embryos were cultured with CRH/Cort plus OECs or in CM conditioned with OECs pretreated with CRH/Cort (treatment CM). Culture in treatment-CM induced oxidative stress and apoptosis in embryos. Preimplantation embryos expressed GR and Fas at all stages and CRHR1 at the blastocyst stage only. Mouse 4-cell embryos and blastocysts expressed HSD2 but not HSD1. Culture of OECs with CRH/Cort increased their oxidative stress, apoptosis, CRHR1, Fas and FasL while decreasing their GR and growth factors. Blastocyst development in treatment-CM conditioned with OECs from gld mice harboring FasL mutations was superior to treatment-CM conditioned with wild-type mouse OECs. The results suggest that CRH/Cort impairs embryo development indirectly by inducing oviductal apoptosis via activating the Fas system. The insensitivity of preimplantation embryos to CRH and corticosterone is due to, respectively, a lack of CRHR and the exclusive expression of HSD2 that inactivate corticosterone. Not applicable. Although significant, the conclusions were drawn from limited results obtained using mice and thus they need further verification in other species. For example, bovine embryos express both HSD1 and HSD2 at all the preimplantation stages whereas mouse preimplantation embryos express HSD2 exclusively without HSD1. The data are important for our understanding of the mechanisms by which stress affects female reproduction in both human and animals, as early stages of pregnancy are considered more vulnerable to stress than the late stages. This study was supported by grants from the National Basic Research Program of China (Nos. 2014CB138503 and 2012CB944403), the China National Natural Science Foundation (Nos. 31272444 and 30972096) and the Animal breeding improvement program of Shandong Province. All authors declare that their participation in the study did not involve factual or potential conflicts of interests. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com

Impact of PACAP and PAC1 Receptor Deficiency on the Neurochemical and Behavioral Effects of Acute and Chronic Restraint Stress in Male C57BL/6 Mice

PubMed Central

Mustafa, Tomris; Jiang, Sunny Zhihong; Eiden, Adrian M.; Weihe, Eberhard; Thistlethwaite, Ian; Eiden, Lee E.

2016-01-01

Acute restraint stress (ARS) for 3 hours causes CORT elevation in venous blood, which is accompanied by Fos up-regulation in the paraventricular nucleus (PVN) of male C57BL/6 mice. CORT elevation by ARS is attenuated in PACAP-deficient mice, but unaffected in PAC1-deficient mice. Correspondingly, Fos up-regulation by ARS is greatly attenuated in PACAP-deficient mice, but much less so in PAC1-deficient animals. We noted that both PACAP- and PAC1-deficiency greatly attenuate CORT elevation after ARS when CORT measurements are performed on trunk blood following euthanasia by abrupt cervical separation: this latter observation is of critical importance in assessing the role of PACAP neurotransmission in ARS, based on previous reports in which serum CORT was sampled from trunk blood. Seven days of chronic restraint stress (CRS) induces non-habituating CORT elevation, and weight loss consequent to hypophagia, in wild-type male C57BL/6 mice. Both CORT elevation and weight loss following seven day CRS are severely blunted in PACAP-deficient mice, but only slightly in PAC1 deficient mice. However, longer periods of daily restraint (14–21 days) resulted in sustained weight loss and elevated CORT in wild-type mice, and these effects of long-term chronic stress were attenuated or abolished in both PACAP- and PAC1-deficient mice. We conclude that while a PACAP receptor in addition to PAC1 may mediate some of the PACAP-dependent central effects of acute restraint stress and short-term (<7 days) chronic restraint stress on the HPA axis, the PAC1 receptor plays a prominent role in mediating PACAP-dependent HPA axis activation, and hypophagia, during long-term (>7 days) chronic restraint stress. PMID:25853791

Early paternal deprivation alters levels of hippocampal brain-derived neurotrophic factor and glucocorticoid receptor and serum corticosterone and adrenocorticotropin in a sex-specific way in socially monogamous mandarin voles.

PubMed

Wu, Ruiyong; Song, Zhenzhen; Wang, Siyang; Shui, Li; Tai, Fadao; Qiao, Xufeng; He, Fengqin

2014-01-01

In monogamous mammals, fathers play an important role in the development of the brain and typical behavior in offspring, but the exact nature of this process is not well understood. In particular, little research has addressed whether the presence or absence of paternal care alters levels of hippocampal glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF), and basal levels of serum corticosterone (CORT) and adrenocorticotropin (ACTH). Here, we explored this concept using socially monogamous mandarin voles (Microtus mandarinus), a species in which fathers display high levels of paternal care toward their pups. Our immunohistochemical study shows that paternal deprivation (PD) significantly decreased levels of GR and BDNF protein in the CA1 and CA2/3 of the hippocampus. In the dental gyrus, decreases in GR and BDNF induced by PD were evident in females but not in males. Additionally, enzyme-linked immunosorbent assay results show that PD significantly upregulated levels of serum CORT and ACTH in females, but not males. These findings demonstrate that PD alters HPA axis activity in a sex-specific way. The changes in stress hormones documented here may be associated with alteration in hippocampal BDNF and GR levels. © 2014 S. Karger AG, Basel.

Balancing personal maintenance with parental investment in a chick-rearing seabird: physiological indicators change with foraging conditions.

PubMed

Storey, Anne E; Ryan, Morag G; Fitzsimmons, Michelle G; Kouwenberg, Amy-Lee; Takahashi, Linda S; Robertson, Gregory J; Wilhelm, Sabina I; McKay, Donald W; Herzberg, Gene R; Mowbray, Frances K; MacMillan, Luke; Walsh, Carolyn J

2017-01-01

Seabird parents use a conservative breeding strategy that favours long-term survival over intensive parental investment, particularly under harsh conditions. Here, we examine whether variation in several physiological indicators reflects the balance between parental investment and survival in common murres ( Uria aalge ) under a wide range of foraging conditions. Blood samples were taken from adults during mid-chick rearing from 2007 to 2014 and analysed for corticosterone (CORT, stress hormone), beta-hydroxybutyrate (BUTY, lipid metabolism reflecting ongoing mass loss), and haematocrit (reflecting blood oxygen capacity). These measures, plus body mass, were related to three levels of food availability (good, intermediate, and poor years) for capelin, the main forage fish for murres in this colony. Adult body mass and chick-feeding rates were higher in good years than in poor years and heavier murres were more likely to fledge a chick than lighter birds. Contrary to prediction, BUTY levels were higher in good years than in intermediate and poor years. Murres lose body mass just after their chicks hatch and these results for BUTY suggest that mass loss may be delayed in good years. CORT levels were higher in intermediate years than in good or poor years. Higher CORT levels in intermediate years may reflect the necessity of increasing foraging effort, whereas extra effort is not needed in good years and it is unlikely to increase foraging success in poor years. Haematocrit levels were higher in poor years than in good years, a difference that may reflect either their poorer condition or increased diving requirements when food is less available. Our long-term data set provided insight into how decisions about resource allocation under different foraging conditions are relating to physiological indicators, a relationship that is relevant to understanding how seabirds may respond to changes in marine ecosystems as ocean temperatures continue to rise.

Breeding status affects the hormonal and metabolic response to acute stress in a long-lived seabird, the king penguin.

PubMed

Viblanc, Vincent A; Gineste, Benoit; Robin, Jean-Patrice; Groscolas, René

2016-09-15

Stress responses are suggested to physiologically underlie parental decisions promoting the redirection of behaviour away from offspring care when survival is jeopardized (e.g., when facing a predator). Besides this classical view, the "brood-value hypothesis" suggests that parents' stress responses may be adaptively attenuated to increase fitness, ensuring continued breeding when the relative value of the brood is high. Here, we test the brood-value hypothesis in breeding king penguins (Aptenodytes patagonicus), long-lived seabirds for which the energy commitment to reproduction is high. We subjected birds at different breeding stages (courtship, incubation and chick brooding) to an acute 30-min capture stress and measured their hormonal (corticosterone, CORT) and metabolic (non-esterified fatty acid, NEFA) responses to stress. We found that CORT responses were markedly attenuated in chick-brooding birds when compared to earlier stages of breeding (courtship and incubation). In addition, NEFA responses appeared to be rapidly attenuated in incubating and brooding birds, but a progressive increase in NEFA plasma levels in courting birds suggested energy mobilization to deal with the threat. Our results support the idea that stress responses may constitute an important life-history mechanism mediating parental reproductive decisions in relation to their expected fitness outcome. Copyright © 2016 Elsevier Inc. All rights reserved.

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats.

PubMed

Hu, Xu; Wang, Tao; Luo, Jia; Liang, Shan; Li, Wei; Wu, Xiaoli; Jin, Feng; Wang, Li

2014-09-01

Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period.

Central effect of vasotocin 4 receptor (VT4R/V1aR) antagonists on the stress response and food intake in chicks given neuropeptide Y (NPY).

PubMed

Kuenzel, Wayne J; Hancock, Megan; Nagarajan, Gurueswar; Aman, N Alphonse; Kang, Seong W

2016-05-04

Previous studies identified SR-49059 as a most effective antagonist of the avian vasotocin 4 receptor (VT4R) compared to other candidate blockers including the Manning compound using in silico 3 dimensional (3D) modeling/docking analysis of the chicken VT4R and an in vitro anterior pituitary cell culture study. The present experiments were designed to validate whether SR-49059 and the Manning compound would likewise be effective in vivo in blocking the VT4R when applied intracerebroventricularly (ICV) to chicks. Two treatments were tested, a stressor (immobilization) and administration of neuropeptide Y (NPY), a potent orexigenic compound. In the first experiment, birds were given the Manning compound, SR-49059 or physiological saline ICV followed by immobilization stress. Blood samples were taken and corticosterone (CORT) was determined by radioimmunoassay. It was hypothesized that both antagonists would reduce the stress response. A second experiment examined the role of the VT4R in food intake regulation. The Manning compound, SR-49059 or physiological saline was administered prior to NPY and food intake was monitored for 1h. It was hypothesized that each of the two antagonists coupled with NPY would augment food intake above the intake resulting from saline plus NPY administration. Related to the second experiment was a third that examined the difference between the effect of central administration of NPY versus SR-49059 in releasing CORT. Results of the first study showed that the Manning compound or SR-49059 prior to stress decreased CORT levels compared to controls while the second experiment showed that SR-49059 or the Manning compound plus NPY, enhanced food intake above that of the experimental group given saline and NPY. The last study showed that NPY increased plasma CORT above birds given SR-49059 centrally or saline administered controls. Taken together, results suggest that the avian VT4R is involved in the central neuroendocrine stress response as well as functions in appetite regulation by mediating an anorexigenic effect similar to what has been reported in mammals for the V1aR. In conclusion, similar to the past in silico and in vitro tests, the current in vivo experiments showed SR-49059 to be a most efficacious avian vasotocin receptor antagonist. Therefore based upon results of functional tests utilizing a highly specific mammalian antagonist, SR-49059, to the mammalian V1aR that likewise was most effective in blocking the avian VT4R and past reported high sequence homology between the mammalian V1aR and the VT4R, it is recommended that the chicken VT4R be renamed the avian V1aR to facilitate better communication among scientists involved in comparative studies. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Activation of GABA-A receptors during postnatal brain development increases anxiety- and depression-related behaviors in a time- and dose-dependent manner in adult mice.

PubMed

Salari, Ali-Akbar; Bakhtiari, Amir; Homberg, Judith R

2015-08-01

Disturbances of the gamma-amino butyric acid-ergic (GABAergic) system during postnatal development can have long-lasting consequences for later life behavior, like the individual's response to stress. However, it is unclear which postnatal windows of sensitivity to GABA-ergic modulations are associated with what later-life behavioral outcomes. Therefore, we sought to determine whether neonatal activation of the GABA-A receptor during two postnatal periods, an early window (postnatal day 3-5) and a late window (postnatal day 14-16), can affect anxiety- and depression-related behaviors in male mice in later life. To this end, mice were treated with either saline or muscimol (50, 100, 200, 300 and 500μg/kg) during the early and late postnatal periods. An additional group of mice was treated with the GABA-A receptor antagonist bicuculline+muscimol. When grown to adulthood male mice were exposed to behavioral tests to measure anxiety- and depression-related behaviors. Baseline and stress-induced corticosterone (CORT) levels were also measured. The results indicate that early postnatal and to a lesser extent later postnatal exposure to the GABA-A receptor agonist muscimol increased anxiety-like behavior and stress-induced CORT levels in adults. Moreover, the early postnatal treatment with muscimol increased depression-like behavior with increasing baseline CORT levels. The anxiogenic and depression-like later-life consequences could be antagonized by bicuculline. Our findings suggest that GABA-A receptor signaling during early-life can influence anxiety- and depression-related behaviors in a time- and dose-dependent manner in later life. Our findings help to increase insight in the developmental mechanisms contributing to stress-related disorders. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

Beneficial effects of exercise and its molecular mechanisms on depression in rats

PubMed Central

Zheng, Hang; Liu, Yanyou; Li, Wei; Yang, Bo; Chen, Dengbang; Wang, Xiaojia; Jiang, Zhou; Wang, Hongxing; Wang, Zhengrong; Cornelisson, G.; Halberg, F.

2008-01-01

Exercise showed the beneficial effects on mental health in depressed sufferers, whereas, its underlying mechanisms remained unresolved. This study utilized the chronic unpredictable stress (CNS) animal model of depression to evaluate the effects of exercise on depressive behaviors and spatial performance in rats. Furthermore, we tested the hypothesis that the capacity of exercise to reverse the harmful effects of CNS was relative to the hypothalamo–pituitary–adrenal (HPA) system and brain-derived neurotrophic factor (BDNF) in the hippocampus. Animal groups were exposed to CNS for 4 weeks with and without access to voluntary wheel running. Stressed rats consumed significantly less of a 1% sucrose solution during CNS and exhibited a significant decrease in open field behavior. On the other hand, they showed impaired spatial performance in Morris water maze test 2 weeks after the end of CNS. Further, CNS significantly decreased hippocampal BDNF mRNA levels. However, voluntary exercise improved or even reversed these harmful behavioral effects in stressed rats. Furthermore, exercise counteracted a decrease in hippocampal BDNF mRNA caused by CNS. In addition, we also found that CMS alone increased circulating corticosterone (CORT) significantly and decreased hippocampal glucocorticoid receptor (GR) mRNA. At the same time, exercise alone increased CORT moderately and did not affect hippocampal GR mRNA levels. While, when both CNS and exercise were combined, exercise reduced the increase of CORT and the decrease of GR caused by CMS. The results demonstrated that: (1) exercise reversed the harmful effects of CNS on mood and spatial performance in rats and (2) the behavioral changes induced by exercise and/or CNS might be associated with hippocampal BDNF levels, and in addition, the HPA system might play different roles in the two different processes. PMID:16290283

Evaluating the stress response as a bioindicator of sub-lethal effects of crude oil exposure in wild house sparrows (Passer domesticus).

PubMed

Lattin, Christine R; Ngai, Heather M; Romero, L Michael

2014-01-01

Petroleum can disrupt endocrine function in humans and wildlife, and interacts in particularly complex ways with the hypothalamus-pituitary-adrenal (HPA) axis, responsible for the release of the stress hormones corticosterone and cortisol (hereafter CORT). Ingested petroleum can act in an additive fashion with other stressors to cause increased mortality, but it is not clear exactly why--does petroleum disrupt feedback mechanisms, stress hormone production, or both? This laboratory study aimed to quantify the effects of ingested Gulf of Mexico crude oil on the physiological stress response of house sparrows (Passer domesticus). We examined baseline and stress-induced CORT, negative feedback, and adrenal sensitivity in house sparrows given a 1% oil or control diet (n = 12 in each group). We found that four weeks on a 1% oil diet did not alter baseline CORT titers or efficacy of negative feedback, but significantly reduced sparrows' ability to secrete CORT in response to a standardized stressor and adrenocorticotropin hormone injection, suggesting that oil damages the steroid-synthesizing cells of the adrenal. In another group of animals on the same 1% oil (n = 9) or control diets (n = 8), we examined concentrations of eight different blood chemistry parameters, and CORT in feathers grown before and during the feeding experiments as other potential biomarkers of oil exposure. None of the blood chemistry parameters differed between birds on the oil and control diets after two or four weeks of feeding, nor did feather CORT differ between the two groups. Overall, this study suggests that the response of CORT to stressors, but not baseline HPA function, may be a particularly sensitive bioindicator of sub-lethal chronic effects of crude oil exposure.

Evaluating the Stress Response as a Bioindicator of Sub-Lethal Effects of Crude Oil Exposure in Wild House Sparrows (Passer domesticus)

PubMed Central

Lattin, Christine R.; Ngai, Heather M.; Romero, L. Michael

2014-01-01

Petroleum can disrupt endocrine function in humans and wildlife, and interacts in particularly complex ways with the hypothalamus-pituitary-adrenal (HPA) axis, responsible for the release of the stress hormones corticosterone and cortisol (hereafter CORT). Ingested petroleum can act in an additive fashion with other stressors to cause increased mortality, but it is not clear exactly why—does petroleum disrupt feedback mechanisms, stress hormone production, or both? This laboratory study aimed to quantify the effects of ingested Gulf of Mexico crude oil on the physiological stress response of house sparrows (Passer domesticus). We examined baseline and stress-induced CORT, negative feedback, and adrenal sensitivity in house sparrows given a 1% oil or control diet (n = 12 in each group). We found that four weeks on a 1% oil diet did not alter baseline CORT titers or efficacy of negative feedback, but significantly reduced sparrows' ability to secrete CORT in response to a standardized stressor and adrenocorticotropin hormone injection, suggesting that oil damages the steroid-synthesizing cells of the adrenal. In another group of animals on the same 1% oil (n = 9) or control diets (n = 8), we examined concentrations of eight different blood chemistry parameters, and CORT in feathers grown before and during the feeding experiments as other potential biomarkers of oil exposure. None of the blood chemistry parameters differed between birds on the oil and control diets after two or four weeks of feeding, nor did feather CORT differ between the two groups. Overall, this study suggests that the response of CORT to stressors, but not baseline HPA function, may be a particularly sensitive bioindicator of sub-lethal chronic effects of crude oil exposure. PMID:25029334

Constant light disrupts the circadian rhythm of steroidogenic proteins in the rat adrenal gland.

PubMed

Park, Shin Y; Walker, Jamie J; Johnson, Nicholas W; Zhao, Zidong; Lightman, Stafford L; Spiga, Francesca

2013-05-22

The circadian rhythm of corticosterone (CORT) secretion from the adrenal cortex is regulated by the suprachiasmatic nucleus (SCN), which is entrained to the light-dark cycle. Since the circadian CORT rhythm is associated with circadian expression of the steroidogenic acute regulatory (StAR) protein, we investigated the 24h pattern of hormonal secretion (ACTH and CORT), steroidogenic gene expression (StAR, SF-1, DAX1 and Nurr77) and the expression of genes involved in ACTH signalling (MC2R and MRAP) in rats entrained to a normal light-dark cycle. We found that circadian changes in ACTH and CORT were associated with the circadian expression of all gene targets; with SF-1, Nurr77 and MRAP peaking in the evening, and DAX1 and MC2R peaking in the morning. Since disruption of normal SCN activity by exposure to constant light abolishes the circadian rhythm of CORT in the rat, we also investigated whether the AM-PM variation of our target genes was also disrupted in rats exposed to constant light conditions for 5weeks. We found that the disruption of the AM-PM variation of ACTH and CORT secretion in rats exposed to constant light was accompanied by a loss of AM-PM variation in StAR, SF-1 and DAX1, and a reversed AM-PM variation in Nurr77, MC2R and MRAP. Our data suggest that circadian expression of StAR is regulated by the circadian expression of nuclear receptors and proteins involved in both ACTH signalling and StAR transcription. We propose that ACTH regulates the secretion of CORT via the circadian control of steroidogenic gene pathways that become dysregulated under the influence of constant light. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Altered GABAergic and glutamatergic activity within the rat hippocampus and amygdala in rats subjected to repeated corticosterone administration but not restraint stress.

PubMed

Lussier, A L; Romay-Tallón, R; Caruncho, H J; Kalynchuk, L E

2013-02-12

We investigated the effect of two well characterized preclinical animal models of depression - repeated injections of corticosterone (CORT) and repeated restraint stress - on markers of GABAergic and glutamatergic activity in the hippocampus and amygdala. Stress is an identified risk factor for the onset of major depression, but the neurobiological mechanisms by which stress may produce depressogenic effects are not clear. Rats received one of the following four treatments for 21 consecutive days: daily single CORT injections (40mg/kg), daily single vehicle injections, daily 6h of restraint stress, or daily handling. After the 21-day stress period, all rats were sacrificed and hippocampal and amygdalar tissue was collected and prepared for Western blot analyses. We examined the effect of CORT and restraint stress on glutamate decarboxylase (GAD)-65 and GAD67, as well as the α1, α2, α3, and β2-3 GABA(A) receptor subunits, and the vesicular glutamate transporter (VGLUT)-2. We found that CORT significantly decreased GAD65 and the α2 receptor subunit and increased VGLUT2 within the hippocampus. We also found that CORT decreased GAD67 and the α2 receptor subunit in the amygdala. However, restraint stress had no significant effect on protein expression in either the hippocampus or the amygdala. These findings parallel our previous results showing that repeated CORT injections, but not restraint stress, increase depression-like behavior in rats, and suggest that the depressogenic effects of CORT may be related to alterations in GABAergic and glutamatergic neurotransmission in stress-sensitive regions of the brain. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Antistress Effects of Rosa rugosa Thunb. on Total Sleep Deprivation-Induced Anxiety-Like Behavior and Cognitive Dysfunction in Rat: Possible Mechanism of Action of 5-HT6 Receptor Antagonist.

PubMed

Na, Ju-Ryun; Oh, Dool-Ri; Han, SeulHee; Kim, Yu-Jin; Choi, EunJin; Bae, Donghyuck; Oh, Dong Hwan; Lee, Yoo-Hyun; Kim, Sunoh; Jun, Woojin

2016-09-01

Our previous results suggest that the Rosa rugosa Thunb. (family Rosaceae) alleviates endurance exercise-induced stress by decreasing oxidative stress levels. This study aimed to screen and identify the physiological antistress effects of an extract of R. rugosa (RO) on sleep deprivation-induced anxiety-like behavior and cognitive tests (in vivo) and tested for hippocampal CORT and monoamine levels (ex vivo), corticosterone (CORT)-induced injury, N-methyl-d-aspartate (NMDA) receptor, and serotonin 6 (5-hydroxytryptamine 6, 5-HT6) receptor activities (in vitro) in search of active principles and underlying mechanisms of action. We confirmed the antistress effects of RO in a sleep-deprived stress model in rat and explored the underlying mechanisms of its action. In conclusion, an R. rugosa extract showed efficacy and potential for use as an antistress therapy to treat sleep deprivation through its antagonism of the 5-HT6 receptor and resulting inhibition of cAMP activity.

Influence of temperature on the corticosterone stress-response: an experiment in the Children's python (Antaresia childreni).

PubMed

Dupoué, Andréaz; Brischoux, François; Lourdais, Olivier; Angelier, Frédéric

2013-11-01

To cope with environmental challenges, organisms have to adjust their behaviours and their physiology to the environmental conditions they face (i.e. allostasis). In vertebrates, such adjustments are often mediated through the secretion of glucocorticoids (GCs) that are well-known to activate and/or inhibit specific physiological and behavioural traits. In ectothermic species, most processes are temperature-dependent and according to previous studies, low external temperatures should be associated with low GC concentrations (both baseline and stress-induced concentrations). In this study, we experimentally tested this hypothesis by investigating the short term influence of temperature on the GC stress response in a squamate reptile, the Children's python (Antaresia childreni). Snakes were maintained in contrasting conditions (warm and cold groups), and their corticosterone (CORT) stress response was measured (baseline and stress-induced CORT concentrations), within 48h of treatment. Contrary to our prediction, baseline and stress-induced CORT concentrations were higher in the cold versus the warm treatment. In addition, we found a strong negative relationship between CORT concentrations (baseline and stress-induced) and temperature within the cold treatment. Although it remains unclear how cold temperatures can mechanistically result in increased CORT concentrations, we suggest that, at suboptimal temperature, high CORT concentrations may help the organism to maintain an alert state. Copyright © 2013 Elsevier Inc. All rights reserved.

Does translocation influence physiological stress in the desert tortoise?

USGS Publications Warehouse

Drake, K.K.; Nussear, K.E.; Esque, T.C.; Barber, A.M.; Vittum, K.M.; Medica, P.A.; Tracy, C.R.; Hunter, K.W.

2012-01-01

Wildlife translocation is increasingly used to mitigate disturbances to animals or habitat due to human activities, yet little is known about the extent to which translocating animals causes stress. To understand the relationship between physiological stress and translocation, we conducted a multiyear study (2007–2009) using a population of desert tortoises (Gopherus agassizii) near Fort Irwin, California. Blood samples were collected from adult tortoises in three treatment groups (resident, translocated and control) for 1 year prior to and 2 years after translocation. Samples were analyzed by radioimmunoassay for plasma total corticosterone (CORT), a glucocorticoid hormone commonly associated with stress responses in reptiles. CORT values were analyzed in relation to potential covariates (animal sex, date, behavior, treatment, handling time, air temperature, home-range size, precipitation and annual plant production) among seasons and years. CORT values in males were higher than in females, and values for both varied monthly throughout the activity season and among years. Year and sex were strong predictors of CORT, and translocation explained little in terms of CORT. Based on these results, we conclude that translocation does not elicit a physiological stress response in desert tortoises.

Experimental occlusal disharmony - A promoting factor for anxiety in rats under chronic psychological stress.

PubMed

Tang, Xuan; Li, Jian; Jiang, Ting; Han, Shu-Hui; Yao, Dong-Yuan

2017-04-03

Clinically, patients under chronic psychological stress (PS) appear to be more susceptible to occlusal disharmony (OD) compared with those without PS. OD was proved to introduce anxiety-like stress. Therefore, the purpose of the study was to investigate whether OD would affect psychological stress-induced anxiety and its underlying mechanisms. Chronic PS was induced by a communication box, and OD was produced by bonding a 0.3mm-thick crown on the right maxillary first molar of male Sprague-Dawley rats. Sixty-seven rats were randomly divided into 8 groups: (A) chronic PS plus OD group (n=6); (B) chronic PS plus sham OD group (n=6); (C) chronic PS only group (n=6); (D) OD group (n=6); (E) sham OD group (n=6); (F) control group (n=6); (G) naive group (n=6); (H) foot-shock group (n=25). Open-field test (OFT) and elevated plus maze test (EPM) were conducted on the 7th, 21th, 35th day to measure the anxiety level of each group except naive and foot-shock group. In addition, corticosterone (CORT) level in serum, 5-hydroxytryptamine (5-HT) and 5-HT 2A receptor (5-HT 2A R) expressions in prefrontal cortex (PFC), hippocampal CA1 and dentate gyrus (DG) areas were measured on the 35th day to elucidate the mechanism(s) by which the exacerbation occurred. The significant differences in OFT and EPM tests on day 21 or day 35 between groups (p<0.01) indicated the successful establishment of animal model of PS or OD. And there was a significant increase in CORT concentration in serum (p<0.01), 5-HT expressions in PFC, hippocampal DG areas and 5-HT 2A R expressions in PFC, hippocampal CA1 areas (p<0.05) in group A, B, C, D compared with group F. Similar results were also found in group A, B, C, D when compared with group G (p<0.05) except 5-HT expression in DG area in group C and D (p>0.05), together with a gradual decrease in values of all the parameters mentioned above from group A to group G. The significant changes in exploratory behaviors, serum CORT concentration, 5-HT and 5-HT 2A R expressions induced by OD in rats with or without chronic PS, and more obvious alterations in rats with chronic PS, may indicate that OD may be a promoting factor for anxiety through both peripheral and central pathways via the hypothalamus-pituitary-adrenal (HPA) axis and 5-HT system. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular mechanisms of corticosteroid synergy with thyroid hormone during tadpole metamorphosis

PubMed Central

Bonett, Ronald M.; Hoopfer, Eric D.; Denver, Robert J.

2010-01-01

Corticosteroids (CS) act synergistically with thyroid hormone (TH) to accelerate amphibian metamorphosis. Earlier studies showed that CS increase nuclear 3,5,3′-triiodothyronine (T3) binding capacity in tadpole tail, and 5′ deiodinase activity in tadpole tissues, increasing the generation of T3 from thyroxine (T4). In the present study we investigated CS synergy with TH by analyzing expression of key genes involved in TH and CS signaling using tadpole tail explant cultures, prometamorphic tadpoles, and frog tissue culture cells (XTC-2 and XLT-15). Treatment of tail explants with T3 at 100 nM, but not at 10 nM caused tail regression. Corticosterone (CORT) at three doses (100, 500, 3400 nM) had no effect or increased tail size. T3 at 10 nM plus CORT caused tails to regress similar to 100 nM T3. Thyroid hormone receptor beta (TRβ) mRNA was synergistically upregulated by T3 plus CORT in tail explants, tail and brain in vivo, and tissue culture cells. The activating 5′ deiodinase type 2 (D2) mRNA was induced by T3 and CORT in tail explants and tail in vivo. Thyroid hormone increased expression of glucocorticoid (GR) and mineralocorticoid receptor (MR) mRNAs. Our findings support that the synergistic actions of TH and CS in metamorphosis occur at the level of expression of genes for TRβ and D2, enhancing tissue sensitivity to TH. Concurrently, TH enhances tissue sensitivity to CS by upregulating GR and MR. Environmental stressors can modulate the timing of tadpole metamorphosis in part by CS enhancing the response of tadpole tissues to the actions of TH. PMID:20338173

Evidence for baseline glucocorticoids as mediators of reproductive investment in a wild bird.

PubMed

Love, Oliver P; Madliger, Christine L; Bourgeon, Sophie; Semeniuk, Christina A D; Williams, Tony D

2014-04-01

Determining the mechanisms that mediate investment decisions between current and future reproductive attempts is still a key goal of life-history studies. Since baseline levels of stress hormones (glucocorticoids - GCs) act as predictive and labile regulators of daily energetic balance in vertebrates they remain excellent candidates for mediating investment decisions both within and across reproductive attempts. Using free-living female European starlings (Sturnus vulgaris) we experimentally reduced investment in current reproduction (number of offspring raised in the first brood) to examine whether baseline corticosterone (CORT) acted as a hormonal mediator preparing individuals for a predictable increase in future investment (number of offspring raised in the second brood). Although treatment and control birds raised the same total amount of offspring across two broods, the experimental birds increased reproductive investment in second broods to compensate for the reduced investment in the first brood. Data on both mean and intra-individual changes in baseline CORT support the idea that an increase in baseline CORT between the incubation stages in treatment birds strongly predicted this increase in investment. Importantly, we measured the increase in baseline CORT during late incubation prior to the increase in energetic demand associated with increased reproductive investment in offspring, indicating that flexible within-individual changes in baseline GCs can act as a labile mechanism preparing individuals for predictable increases in reproductive investment. As such, our experimental results indicate that elevated baseline GCs can prepare individuals for investment in energetically expensive life-history stages, rather than simply being elevated as a consequence of increased effort or demand. This suggests that short-term preparative increases in baseline GCs benefit individuals by successfully allowing them to maximize fitness under varying environmental conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

The Endocrine Disrupting Chemical Tolylfluanid Alters Adipocyte Metabolism via Glucocorticoid Receptor Activation

PubMed Central

Neel, Brian A.; Brady, Matthew J.

2013-01-01

Glucocorticoid signaling plays a critical role in regulating energy metabolism. Emerging data implicate environmental endocrine-disrupting chemicals as contributors to the obesity and diabetes epidemics. Previous studies have shown that the phenylsulfamide fungicide tolylfluanid (TF) augments glucocorticoid receptor (GR)-dependent luciferase expression in 3T3-L1 preadipocytes while modulating insulin action in primary murine and human adipocytes. Studies were performed to interrogate glucocorticoid signaling in primary adipocytes exposed to TF. TF mimicked the gene transcription profile of the murine glucocorticoid corticosterone (Cort). Cellular fractionation assays demonstrated that TF treatment promoted the activating serine phosphorylation of GR, augmenting its cytoplasmic-to-nuclear translocation as well as its enrichment at glucocorticoid response elements on the glucocorticoid-induced leucine zipper gene promoter. After acute treatment, Cort or TF promoted insulin receptor substrate-1 (IRS-1) gene and protein expression. Either treatment also enriched GR binding at an identified glucocorticoid response element in the IRS-1 gene. TF or Cort each increased insulin-stimulated lipogenesis, an effect resulting from increased lipogenic gene expression and enhanced insulin-stimulated dephosphorylation of acetyl-coenzyme A carboxylase. The augmentation of insulin-stimulated lipogenesis was mediated through a specific enhancement of Akt phosphorylation at T308. These findings support modulation of IRS-1 levels as a mechanism for glucocorticoid-mediated changes in insulin action in primary adipocytes. Albeit with less affinity than Cort, in silico analysis suggests that TF can interact with the ligand binding pocket of GR. Collectively, these studies identify TF as a structurally unique environmental glucocorticoid. Glucocorticoid signaling may thus represent a novel pathway by which environmental toxicants promote the development of metabolic diseases. PMID:23340252

Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis.

PubMed

Donner, Nina C; Siebler, Philip H; Johnson, Danté T; Villarreal, Marcos D; Mani, Sofia; Matti, Allison J; Lowry, Christopher A

2016-01-01

Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme's diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2 activity in the DRD/DRC furthermore predicted TPH2 activity in the amygdala and in the caudal pontine reticular nucleus (PnC), while serotonin synthesis in the PnC was strongly correlated with the maximum startle response. Our data demonstrate that chronically elevated glucocorticoids sensitize stress- and anxiety-related serotonergic systems, and for the first time reveal competing roles of CRHR1 and CRHR2 on stress-induced in vivo serotonin synthesis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Serotonergic systems in the balance: CRHR1 and CRHR2 differentially control stress-induced serotonin synthesis

PubMed Central

Donner, Nina C.; Siebler, Philip H.; Johnson, Danté T.; Villarreal, Marcos D.; Mani, Sofia; Matti, Allison J.; Lowry, Christopher A.

2015-01-01

Anxiety and affective disorders are often associated with hypercortisolism and dysfunctional serotonergic systems, including increased expression of TPH2, the gene encoding the rate-limiting enzyme of neuronal serotonin synthesis. We previously reported that chronic glucocorticoid exposure is anxiogenic and increases rat Tph2 mRNA expression, but it was still unclear if this also translates to increased TPH2 protein levels and in vivo activity of the enzyme. Here, we found that adult male rats treated with corticosterone (CORT, 100 μg/ml) via the drinking water for 21 days indeed show increased TPH2 protein expression in the dorsal and ventral part of the dorsal raphe nucleus (DRD, DRV) during the light phase, abolishing the enzyme’s diurnal rhythm. In a second study, we systemically blocked the conversion of 5-hydroxytryptophan (5-HTP) to serotonin immediately before rats treated with CORT or vehicle were either exposed to 30 min acoustic startle stress or home cage control conditions. This allowed us to measure 5-HTP accumulation as a direct readout of basal versus stress-induced in vivo TPH2 activity. As expected, basal TPH2 activity was elevated in the DRD, DRV and MnR of CORT-treated rats. In response to stress, a multitude of serotonergic systems reacted with increased TPH2 activity, but the stress-, anxiety-, and learned helplessness-related dorsal and caudal DR (DRD/DRC) displayed stress-induced increases in TPH2 activity only after chronic CORT-treatment. To address the mechanisms underlying this region-specific CORT-dependent sensitization, we stereotaxically implanted CORT-treated rats with cannulae targeting the DR, and pharmacologically blocked either corticotropin-releasing hormone receptor type 1 (CRHR1) or type 2 (CRHR2) 10 min prior to acoustic startle stress. CRHR2 blockade prevented stress-induced increases of TPH2 activity within the DRD/DRC, while blockade of CRHR1 potentiated stress-induced TPH2 activity in the entire DR. Stress-induced TPH2 activity in the DRD/DRC furthermore predicted TPH2 activity in the amygdala and in the caudal pontine reticular nucleus (PnC), while serotonin synthesis in the PnC was strongly correlated with the maximum startle response. Our data demonstrate that chronically elevated glucocorticoids sensitize stress- and anxiety-related serotonergic systems, and for the first time reveal competing roles of CRHR1 and CRHR2 on stress-induced in vivo serotonin synthesis. PMID:26454419

Stress physiology of migrant birds during stopover in natural and anthropogenic woodland habitats of the Northern Prairie region.

PubMed

Liu, Ming; Swanson, David L

2014-01-01

Anthropogenic alterations of woodland habitat may influence stopover biology, which in turn could alter the stress physiology of migratory landbirds. Woodland stopover habitats are scarce in the Northern Prairie region of North America and consist of native riparian corridor woodlands (corridors) and smaller, more isolated woodlots of anthropogenic origin around farmsteads (woodlots). Corridor habitats have been greatly reduced since the time of European settlement, but woodlot habitats have appeared over this same time period. In this study, we compared stopover biology and stress physiology of migratory landbirds using natural and anthropogenic woodland habitats. We first tested for differences between birds in the two habitats for baseline corticosterone (CORTB) and the magnitude of the stress response for individual species, taxonomic families and foraging guilds. Plasma corticosterone increased significantly for all bird groups in both habitats following 30 min of restraint stress (CORT30), and neither CORTB nor the magnitude of the stress response (CORT30 - CORTB) differed significantly between birds in the two habitats. Secondly, because CORTB levels are often elevated and CORT secretion following a stressor is often suppressed for birds in poor body condition, we hypothesized that woodland migrants with higher fattening rates would show reduced CORTB and a robust stress response. We tested this hypothesis by assessing the relationships between plasma corticosterone and plasma metabolites associated with refuelling. We found that CORTB was negatively associated and the magnitude of the stress response positively associated with plasma triglycerides (an indicator of fat deposition), with opposite patterns for corticosterone and plasma β-hydroxybutyrate (an indicator of fat catabolism). These data suggest that both corridor and woodlot habitats serve as effective stopover habitat and that the reduction of corridor habitat and increased reliance on anthropogenic woodlots is not detrimental to the stress physiology of migrants in a region with limited woodland habitats.

The Effects of the First Part of the CoRT Program for Teaching Thinking (BREADTH) on the Development of Communication Skills among a Sample of Students from Al al-Bayt University in Jordan

ERIC Educational Resources Information Center

Alshurman, Wael Mohammad

2017-01-01

This study aimed to investigate the effects of the first part of the CoRT program for teaching thinking (BREADTH) on the development of communication skills among a sample of students from Al al-Bayt University in Jordan. The study sample consisted of all the students enrolled in the training session for the first part of the CoRT program held by…

Effects of Selective and Non-Selective Glucocorticoid Receptor II Antagonists on Rapid-Onset Diabetes in Young Rats

PubMed Central

Beaudry, Jacqueline L.; Dunford, Emily C.; Teich, Trevor; Zaharieva, Dessi; Hunt, Hazel; Belanoff, Joseph K.; Riddell, Michael C.

2014-01-01

The blockade of glucocorticoid (GC) action through antagonism of the glucocorticoid receptor II (GRII) has been used to minimize the undesirable effects of chronically elevated GC levels. Mifepristone (RU486) is known to competitively block GRII action, but not exclusively, as it antagonizes the progesterone receptor. A number of new selective GRII antagonists have been developed, but limited testing has been completed in animal models of overt type 2 diabetes mellitus. Therefore, two selective GRII antagonists (C113176 and C108297) were tested to determine their effects in our model of GC-induced rapid-onset diabetes (ROD). Male Sprague-Dawley rats (∼ six weeks of age) were placed on a high-fat diet (60%), surgically implanted with pellets containing corticosterone (CORT) or wax (control) and divided into five treatment groups. Each group was treated with either a GRII antagonist or vehicle for 14 days after surgery: CORT pellets (400 mg/rat) + antagonists (80 mg/kg/day); CORT pellets + drug vehicle; and wax pellets (control) + drug vehicle. After 10 days of CORT treatment, body mass gain was increased with RU486 (by ∼20% from baseline) and maintained with C113176 administration, whereas rats given C108297 had similar body mass loss (∼15%) to ROD animals. Fasting glycemia was elevated in the ROD animals (>20 mM), normalized completely in animals treated with RU486 (6.2±0.1 mM, p<0.05) and improved in animals treated with C108297 and C113176 (14.0±1.6 and 8.8±1.6 mM, p<0.05 respectively). Glucose intolerance was normalized with RU486 treatment, whereas acute insulin response was improved with RU486 and C113176 treatment. Also, peripheral insulin resistance was attenuated with C113176 treatment along with improved levels of β-cell function while C108297 antagonism only provided modest improvements. In summary, C113176 is an effective agent that minimized some GC-induced detrimental metabolic effects and may provide an alternative to the effective, but non-selective, GRII antagonist RU486. PMID:24642683

Mono-(2-ethylhexyl) phthalate (MEHP) regulates glucocorticoid metabolism through 11{beta}-hydroxysteroid dehydrogenase 2 in murine gonadotrope cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hong, Dun; Department of Orthopedics, Taizhou Hospital, Wenzhou Medical College, Lin Hai, ZJ 317000; Li, Xing-Wang

2009-11-13

Di-(2-ethylhexyl) phthalate (DEHP) and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) have been classified as toxicants to the reproductive system at the testis level and DEHP may also impair reproductive axis function at the pituitary levels. However, MEHP is 10-fold more potent than DEHP in toxicity and little is known about the toxicological effect of MEHP on pituitary. In this study, we demonstrated that 11{beta}-hydroxysteroid dehydrogenase type 2 (11{beta}-HSD2), not 11{beta}-HSD1, is strongly expressed in murine gonadotrope L{beta}T2 cells. Interestingly, MEHP inhibited Hsd11b2 mRNA level and 11{beta}-HSD2 enzyme activity in L{beta}T2 cells at as low as 10{sup -7} M. Corticosterone (CORT) atmore » a concentration of 10{sup -6} M significantly inhibited L{beta}T2 cell proliferation after 2-day culture, and 10{sup -6} M RU486, an antagonist of glucocorticoid receptor (GR), reversed this inhibition. However, in the presence of 10{sup -5} or 10{sup -4} M MEHP, the minimal concentration of CORT to inhibit the proliferation of L{beta}T2 cells was lowered to 10{sup -7} M, and 10{sup -6} M RU486 was not able to completely reverse the CORT effect. In conclusion, along with the regulation of GR, 11{beta}-HSD2 may have a key role in glucocorticoid metabolism in L{beta}T2 cells. MEHP may participate in the glucocorticoid metabolism in L{beta}T2 cells through inhibition of 11{beta}-HSD2 enzyme activity. Such perturbation may be of pathological significance as MEHP may interfere with the reproductive system at pituitary level through regulation of glucocorticoid metabolism, especially in neonates with higher risk of phthalates exposure.« less

Anxiogenic effects of a Lactobacillus, inulin and the synbiotic on healthy juvenile rats.

PubMed

Barrera-Bugueño, Camila; Realini, Ornella; Escobar-Luna, Jorge; Sotomayor-Zárate, Ramón; Gotteland, Martin; Julio-Pieper, Marcela; Bravo, Javier A

2017-09-17

Gut microbiota interventions, including probiotic and prebiotic use can alter behavior in adult animals and healthy volunteers. However, little is known about their effects in younger individuals. To investigate this, male Sprague-Dawley rats (post-natal day 21, PND21) received Lactobacillus casei 54-2-33 (10 4 cfu/ml), inulin as prebiotic (16mg/ml), or both together (synbiotic) via drinking water for 14days. Control rats received water alone. Open field (OF) and elevated plus maze (EPM) behaviors were evaluated at PND34 and 35, respectively. 30min after EPM, brains and trunk blood were collected to evaluate hippocampal 5-HT 1A (mRNA and protein) and plasma corticosterone (CORT). Lactobacillus, inulin and synbiotic-treated rats had fewer entries to the OF's center and spent more time in its periphery than controls. Synbiotic-fed rats explored the EPM's open arms longer than probiotic and inulin-fed rats. Synbiotic, but not Lactobacillus nor inulin-fed rats had lower levels of EPM-evoked CORT than controls. Basal CORT levels, evaluated in a naïve cohort, were higher in Lactobacillus- and inulin-fed rats than controls. In naïve synbiotic-fed rats, 5-HT 1A mRNA levels were higher in dentate gyrus and cornus ammonis 1 layer (CA1), than in all other naïve groups, while hippocampal 5-HT 1A protein levels were lower in bacteria-fed rats than controls. 5-HT 1A mRNA changes suggest complex effects of gut microbes on hippocampal gene expression machinery, probably involving endogenous/exogenous bacteria and prebiotics interactions. Importantly, age might also influence their behavioral outcomes. Together, these data suggest that interventions in young rat microbiota evoke early behavioral changes upon stress, apparently in a hypothalamus-pituitary-adrenal axis independent fashion. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

Depopulation of Caged Layer Hens with a Compressed Air Foam System.

PubMed

Gurung, Shailesh; Hoffman, John; Stringfellow, Kendre; Abi-Ghanem, Daad; Zhao, Dan; Caldwell, David; Lee, Jason; Styles, Darrel; Berghman, Luc; Byrd, James; Farnell, Yuhua; Archer, Gregory; Farnell, Morgan

2018-01-11

During the 2014-2015 US highly pathogenic avian influenza (HPAI) outbreak, 50.4 million commercial layers and turkeys were affected, resulting in economic losses of $3.3 billion. Rapid depopulation of infected poultry is vital to contain and eradicate reportable diseases like HPAI. The hypothesis of the experiment was that a compressed air foam (CAF) system may be used as an alternative to carbon dioxide (CO₂) inhalation for depopulating caged layer hens. The objective of this study was to evaluate corticosterone (CORT) and time to cessation of movement (COM) of hens subjected to CAF, CO₂ inhalation, and negative control (NEG) treatments. In Experiment 1, two independent trials were conducted using young and spent hens. Experiment 1 consisted of five treatments: NEG, CO₂ added to a chamber, a CO₂ pre-charged chamber, CAF in cages, and CAF in a chamber. In Experiment 2, only spent hens were randomly assigned to three treatments: CAF in cages, CO₂ added to a chamber, and aspirated foam. Serum CORT levels of young hens were not significantly different among the CAF in cages, CAF in a chamber, NEG control, and CO₂ inhalation treatments. However, spent hens subjected to the CAF in a chamber had significantly higher CORT levels than birds in the rest of the treatments. Times to COM of spent hens subjected to CAF in cages and aspirated foam were significantly greater than of birds exposed to the CO₂ in a chamber treatment. These data suggest that applying CAF in cages is a viable alternative for layer hen depopulation during a reportable disease outbreak.

Ginsenoside Rg1 exerts synergistic anti-inflammatory effects with low doses of glucocorticoids in vitro.

PubMed

Song, Yanqin; Zhao, Feng; Zhang, Leiming; Du, Yuan; Wang, Tian; Fu, Fenghua

2013-12-01

Glucocorticoids (GCs) are usually used to treat inflammatory diseases. However, they cause severe and irreversible side effects, which limit the use of these compounds. Ginsenoside Rg1 had been demonstrated to possess anti-inflammatory and anti-cancer effects. The present study was designed to investigate whether Rg1 exhibits synergistic anti-inflammatory effects when combined with glucocorticoids. After stimulated by lipopolysaccharide (LPS), murine macrophagic RAW264.7 cells were treated with Rg1, corticosterone (Cort) or Rg1 and Cort. Then nitric oxide (NO), tumor necrosis factor-α (TNF-α) and glucocorticoid receptor (GR) expression were measured. The results showed that Rg1 or Cort could reduce the production of NO and TNF-α, and Rg1 dose-dependently up-regulated GR expression, while Cort dose-dependently down-regulated GR expression. The combination of low concentrations of Rg1 with Cort, which alone could not markedly inhibit the release of inflammatory factors, inhibited the secretion of NO and TNF-α in LPS-stimulated RAW264.7 macrophage cells, and up-regulated the expression of GR. The findings suggested Rg1 can synergize with glucocorticoid to enhance its anti-inflammatory effect. © 2013.

Distress calls of the greater short-nosed fruit bat Cynopterus sphinx activate hypothalamic-pituitary-adrenal (HPA) axis in conspecifics.

PubMed

Mariappan, Subramanian; Bogdanowicz, Wieslaw; Marimuthu, Ganapathy; Rajan, Koilmani Emmanuvel

2013-09-01

In a stressful situation, greater short-nosed fruit bats (Cynopterus sphinx) emit audible vocalization either to warn or to inform conspecifics. We examined the effect of distress calls on bats emitting the call as well as the bats receiving the distress signal through analysis of the hypothalamic-pituitary-adrenal axis and catacholaminargic systems. We measured the levels of neurotransmitters [serotonin (5-HT), dopamine (DA), norepinephrine (NE)] and stress hormones [(adrenocorticotropic hormone (ACTH) and corticosterone (CORT)]. Our results showed that distress call emission elevated the level of ACTH and CORT, as well as 5-HT, DA and NE in the amygdala, for both the call emitting bat and the responding bat. Subsequently, we observed increased activity of glucocorticoid receptor and its steroid receptor co-activator (SRC-1). An expression of SRC-1 was up-regulated in the distress call emitter only, whereas it was at a similar level in both the call responder and silent bats. These findings suggest that bats emitting distress calls and also bats responding to such calls have similar neurotransmitter expression patterns, and may react similarly in response to stress.

Age-dependent effect of high cholesterol diets on anxiety-like behavior in elevated plus maze test in rats

PubMed Central

2014-01-01

Background Cholesterol is an essential component of brain and nerve cells and is essential for maintaining the function of the nervous system. Epidemiological studies showed that patients suffering from anxiety disorders have higher serum cholesterol levels. In this study, we investigated the influence of high cholesterol diet on anxiety-like behavior in elevated plus maze in animal model and explored the relationship between cholesterol and anxiety-like behavior from the aspect of central neurochemical changes. Methods Young (3 weeks old) and adult (20 weeks old) rats were given a high cholesterol diet for 8 weeks. The anxiety-like behavior in elevated plus maze test and changes of central neurochemical implicated in anxiety were measured. Results In young rats, high cholesterol diet induced anxiolytic-like behavior, decreased serum corticosterone (CORT), increased hippocampal brain-derived neurotrophic factor (BDNF), increased hippocampal mineralocorticoid receptor (MR) and decreased glucocorticoid receptor (GR). In adult rats, high cholesterol diet induced anxiety-like behavior and increase of serum CORT and decrease of hippocampal BDNF comparing with their respective control group that fed the regular diet. Discussion High cholesterol diet induced age-dependent effects on anxiety-like behavior and central neurochemical changes. High cholesterol diet might affect the central nervous system (CNS) function differently, and resulting in different behavior performance of anxiety in different age period. PMID:25179125

Depopulation of Caged Layer Hens with a Compressed Air Foam System

PubMed Central

Gurung, Shailesh; Hoffman, John; Stringfellow, Kendre; Abi-Ghanem, Daad; Zhao, Dan; Caldwell, David; Lee, Jason; Styles, Darrel; Berghman, Luc; Byrd, James; Farnell, Yuhua; Archer, Gregory

2018-01-01

Simple Summary Reportable diseases, such as avian influenza, spread rapidly among poultry, resulting in the death of a large number of birds. Once such a disease has been diagnosed at a farm, infected and susceptible birds are rapidly killed to prevent the spread of the disease. The methods to eliminate infected caged laying hens are limited. An experiment was conducted to study the effectiveness of foam made from compressed air, water, and soap to kill laying hens in cages. The study found that stress levels of the hens killed using compressed air foam in cages to be similar to the hens killed by carbon dioxide or the negative control. Hens exposed to carbon dioxide died earlier as compared to the foam methods. The authors conclude that application of compressed air foam in cages is an alternative to methods such as gas inhalation and ventilation shutdown to rapidly and humanely kill laying hens during epidemics. Abstract During the 2014–2015 US highly pathogenic avian influenza (HPAI) outbreak, 50.4 million commercial layers and turkeys were affected, resulting in economic losses of $3.3 billion. Rapid depopulation of infected poultry is vital to contain and eradicate reportable diseases like HPAI. The hypothesis of the experiment was that a compressed air foam (CAF) system may be used as an alternative to carbon dioxide (CO2) inhalation for depopulating caged layer hens. The objective of this study was to evaluate corticosterone (CORT) and time to cessation of movement (COM) of hens subjected to CAF, CO2 inhalation, and negative control (NEG) treatments. In Experiment 1, two independent trials were conducted using young and spent hens. Experiment 1 consisted of five treatments: NEG, CO2 added to a chamber, a CO2 pre-charged chamber, CAF in cages, and CAF in a chamber. In Experiment 2, only spent hens were randomly assigned to three treatments: CAF in cages, CO2 added to a chamber, and aspirated foam. Serum CORT levels of young hens were not significantly different among the CAF in cages, CAF in a chamber, NEG control, and CO2 inhalation treatments. However, spent hens subjected to the CAF in a chamber had significantly higher CORT levels than birds in the rest of the treatments. Times to COM of spent hens subjected to CAF in cages and aspirated foam were significantly greater than of birds exposed to the CO2 in a chamber treatment. These data suggest that applying CAF in cages is a viable alternative for layer hen depopulation during a reportable disease outbreak. PMID:29324639

Chronic corticosterone administration effects on behavioral emotionality in female c57bl6 mice.

PubMed

Mekiri, Maryam; Gardier, Alain M; David, Denis J; Guilloux, Jean-Philippe

2017-04-01

Understanding the pathophysiology of affective disorders and their treatment relies on the availability of experimental models that mimic aspects of the disease. Most of the studies on depressive disorders are conducted with male rodents, mostly because including females in protocols is more difficult. Indeed, there is a complex series of changes in the brain of females due to the estrous cycle, adding an important variability factor to the disease. However, twice as many women as men have a lifetime diagnosis of major depressive disorder (MDD), so we need to develop reliable female models of depression to improve our understanding of this disease. Here, we describe the effects of chronic corticosterone administration (CORT) on female mice, a procedure known to enhance behavioral emotionality in male mice. A dose-response study showed that 4 weeks of CORT exposure at 35 μg/ml in the drinking water enhanced the emotionality score of female mice, but with a very small size effect. Tests of longer treatment duration failed to potentiate the behavioral effects of CORT. As some steps of adult hippocampal neurogenesis are known to be sensitive to chronic CORT exposure, cell proliferation and survival, as well as neuronal maturation in the dentate gyrus of the hippocampus, analyses revealed no effect of chronic CORT exposure in female mice. Overall, this study showed that female C57BL6 mice are insensitive to chronic CORT as a way to model anxio-depressive-like behavior. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Differential effects of voluntary and forced exercise on stress responses after traumatic brain injury.

PubMed

Griesbach, Grace S; Tio, Delia L; Vincelli, Jennifer; McArthur, David L; Taylor, Anna N

2012-05-01

Voluntary exercise increases levels of brain-derived neurotrophic factor (BDNF) after traumatic brain injury (TBI) when it occurs during a delayed time window. In contrast, acute post-TBI exercise does not increase BDNF. It is well known that increases in glucocorticoids suppress levels of BDNF. Moreover, recent work from our laboratory showed that there is a heightened stress response after fluid percussion injury (FPI). In order to determine if a heightened stress response is also observed with acute exercise, at post-injury days 0-4 and 7-11, corticosterone (CORT) and adrenocorticotropic hormone (ACTH) release were measured in rats running voluntarily or exposed to two daily 20-min periods of forced running wheel exercise. Forced, but not voluntary exercise, continuously elevated CORT. ACTH levels were initially elevated with forced exercise, but decreased by post-injury day 7 in the control, but not the FPI animals. As previously reported, voluntary exercise did not increase BDNF in the FPI group as it did in the control animals. Forced exercise did not increase levels of BDNF in any group. It did, however, decrease hippocampal glucocorticoid receptors in the control group. The results suggest that exercise regimens with strong stress responses may not be beneficial during the early post-injury period.

Diagnostic Accuracy of Perioperative Measurement of Basal Anterior Pituitary and Target Gland Hormones in Predicting Adrenal Insufficiency After Pituitary Surgery.

PubMed

Cerina, Vatroslav; Kruljac, Ivan; Radosevic, Jelena Marinkovic; Kirigin, Lora Stanka; Stipic, Darko; Pecina, Hrvoje Ivan; Vrkljan, Milan

2016-03-01

The insulin tolerance test (ITT) is the gold standard for diagnosing adrenal insufficiency (AI) after pituitary surgery. The ITT is unpleasant for patients, requires close medical supervision and is contraindicated in several comorbidities. The aim of this study was to analyze whether tumor size, remission rate, preoperative, and early postoperative baseline hormone concentrations could serve as predictors of AI in order to increase the diagnostic accuracy of morning serum cortisol. This prospective study enrolled 70 consecutive patients with newly diagnosed pituitary adenomas. Thirty-seven patients had nonfunctioning pituitary adenomas (NPA), 28 had prolactinomas and 5 had somatotropinomas. Thyroxin (T4), thyrotropin (TSH), prolactin, follicle-stimulating hormone (FSH), luteinizing hormone (LH), testosterone, and insulin-like growth factor 1 (IGF-I) were measured preoperatively and on the sixth postoperative day. Serum morning cortisol was measured on the third postoperative day (CORT3) as well as the sixth postoperative day (CORT6). Tumor mass was measured preoperatively and remission was assessed 3 months after surgery. An ITT was performed 3 to 6 months postoperatively. Remission was achieved in 48% of patients and AI occurred in 51%. Remission rates and tumor type were not associated with AI. CORT3 had the best predictive value for AI (area under the curve (AUC) 0.868, sensitivity 82.4%, specificity 83.3%). Tumor size, preoperative T4, postoperative T4, and TSH were also associated with AI in a multivariate regression model. A combination of all preoperative and postoperative variables (excluding serum cortisol) had a sensitivity of 75.0% and specificity of 77.8%. The predictive power of CORT3 substantially improved by adding those variables into the model (AUC 0.921, sensitivity 94.1%, specificity 78.3%, PPV 81.9%, NPV of 92.7%). In a subgroup analysis that included only female patients with NPA, LH had exactly the same predictive value as CORT3. The addition of baseline LH to CORT3, increased sensitivity to 100.0%, specificity to 88.9%, PPV to 90.4%, and NPV to 100.0%. Besides CORT3, tumor size, thyroid hormones, and gonadotropins can serve as predictors of AI. LH in postmenopausal female patients with NPA has similar diagnostic accuracy as CORT3. Further studies are needed in order to validate the scoring system proposed by this study.

The Performance of Chinese Primary School Students on Realistic Arithmetic Word Problems

ERIC Educational Resources Information Center

Xin, Ziqiang; Lin, Chongde; Zhang, Li; Yan, Rong

2007-01-01

Compared with standard arithmetic word problems demanding only the direct use of number operations and computations, realistic problems are harder to solve because children need to incorporate "real-world" knowledge into their solutions. Using the realistic word problem testing materials developed by Verschaffel, De Corte, and Lasure…

Intermittent fasting could ameliorate cognitive function against distress by regulation of inflammatory response pathway.

PubMed

Shojaie, Marjan; Ghanbari, Farzane; Shojaie, Nasrin

2017-11-01

Undesirable and desirable effects of stressors on the body are assigned to distress and eustress, respectively. Immune system and brain are the most susceptible parts to stressful conditions, whereas long-lasting alterations in putative immune proteins involved in tension such as corticosterone (CORT), interleukin 6 (IL-6), and tumor necrosis factor-alpha (TNF-α) can impact learning and memory. Intermittent fasting (IF) is a repeated regular cycle of dietary restriction with well-known beneficial properties on the body. The aim of this study was to identify the eustress effects of IF on cognitive function by assessing the critical inflammatory factors in chronic distress. Forty male mice were divided into four groups (n = 10/group). Distress and control normally received food and water, whereas IF and IF with distress groups were daily deprived of food and water for two hours. In the second week, the electrical foot shock was induced to distress and IF with distress groups. Finally, the cognitive functions of all mice were evaluated by Barnes maze, their blood samples were taken to determine the plasma level of CORT, IL-6 and TNF-α, and the removed brain and adrenal glands were weighed in the third week. A significant gain in plasma level of CORT, IL-6 and TNF-α with a considerable brain hypotrophy and adrenal hypertrophy was found in distress group, whereas IF caused a remarkable reduction of the plasma inflammatory factors, especially in IF with distress mice ( P  ≤ 0.05). In conclusion, IF could improve cognitive function and preserve the brain against distress by regulation of inflammatory response pathway.

The role of social isolation in ethanol effects on the preweanling rat

PubMed Central

Kozlov, Andrey P.; Nizhnikov, Michael; Varlinskaya, Elena I.; Spear, Norman E.

2011-01-01

The present experiments investigated the effects of acute ethanol exposure on voluntary intake of 0.1% saccharin or water as well as behavioral and nociceptive reactivity in twelve–day-old (P12) rats exposed to differing levels of isolation. The effects of ethanol emerged only during short-term social isolation (STSI) with different patterns observed in males and females and in pups exposed to saccharin or water. The 0.5 g/kg ethanol dose selectively increased saccharin intake in females, decreased rearing activity in males and attenuated isolation-induced analgesia (IIA) in all water-exposed pups. Ingestion of saccharin decreased IIA, and the 0.5 g/kg ethanol dose further reduced IIA. The 1.0 g/kg ethanol dose, administered either intragastrically or intraparentionally, also decreased IIA in P12 females, but not in P9 pups. A significant correlation between voluntary saccharin intake and baseline nociceptive reactivity was revealed in saline injected animals, saccharin intake was inversely correlated with behavioral activation and latency of reaction to noxious heat after 0.5 g/kg ethanol in females. The 0.5 g/kg ethanol dose did not affect plasma corticosterone (CORT) measured 5 hours after maternal separation or 20 minutes after ethanol injection. Female pups CORT level was inversely correlated with magnitude of IIA that accompanied the first episode of STSI (pretest isolation) 1.5–2 hours before CORT measurement. The present findings suggest that the anxiolytic properties of ethanol are responsible for enhancement of saccharin intake during STSI. Furthermore, differential reactivity of P12 males and females to STSI plays an important role in ethanol effects observed at this age. PMID:22051944

Interaction Effect of Social Isolation and High Dose Corticosteroid on Neurogenesis and Emotional Behavior.

PubMed

Chan, Jackie N-M; Lee, Jada C-D; Lee, Sylvia S P; Hui, Katy K Y; Chan, Alan H L; Fung, Timothy K-H; Sánchez-Vidaña, Dalinda I; Lau, Benson W-M; Ngai, Shirley P-C

2017-01-01

Hypercortisolemia is one of the clinical features found in depressed patients. This clinical feature has been mimicked in animal studies via application of exogenous corticosterone (CORT). Previous studies suggested that CORT can induce behavioral disturbance in anxious-depressive like behavior, which is associated with suppressed neurogenesis. Hippocampal neurogenesis plays an important role in adult cognitive and behavioral regulation. Its suppression may thus lead to neuropsychiatric disorders. Similar to the effects of CORT on the animals' depression-like behaviors and neurogenesis, social deprivation has been regarded as one factor that predicts poor prognosis in depression. Furthermore, social isolation is regarded as a stressor to social animals including experimental rodents. Hence, this study aims to examine if social isolation would induce further emotional or anxiety-like behavior disturbance and suppress neurogenesis in an experimental model that was repeatedly treated with CORT. Sprague-Dawley rats were used in this study to determine the effects of different housing conditions, either social isolated or group housing, in vehicle-treated control and CORT-treated animals. Forced swimming test (FST), open field test (OFT) and social interaction test (SIT) were used to assess depression-like, anxiety-like and social behaviors respectively. Immunohistochemistry was performed to quantify the number of proliferative cells and immature neurons in the hippocampus, while dendritic maturation of immature neurons was analyzed by Sholl analysis. Social isolation reduced latency to immobility in FST. Furthermore, social isolation could significantly reduce the ratio of doublecortin and bromodeoxyuridine (BrdU) positive cells of the neurogenesis assay under CORT-treated condition. The current findings suggested that the behavioral and neurological effect of social isolation is dependent on the condition of hypercortisolemia. Furthermore, social isolation may possibly augment the signs and symptoms of depressed patients with potential alteration in neurogenesis.

Chlorotriazine Herbicides and Metabolites Activate an ACTH-Dependent Release of Corticosterone in Male Wistar Rats

EPA Science Inventory

Previously, we reported that atrazine (ATR) alters steroidogenesis in male Wistar rats resulting in elevated serum corticosterone (CORT), progesterone, and estrogens. The increase in CORT indicated that this chlorotriazine herbicide may alter the hypothalamic-pituitary-adrenal ax...

Impact of water temperature and stressor controllability on swim stress-induced changes in body temperature, serum corticosterone, and immobility in rats.

PubMed

Drugan, Robert C; Eren, Senem; Hazi, Agnes; Silva, Jennifer; Christianson, John P; Kent, Stephen

2005-10-01

The present study compared the effects of three different water temperatures (20, 25, and 30 degrees C) and stressor controllability on several physiological and behavioral endpoints in an intermittent swim stress paradigm. The escape latency of rats in the 20 and 25 degrees C water was less than that observed for the 30 degrees C group. Both escape and yoked groups at 20 and 25 degrees C exhibited moderate to severe hypothermia following the swim stress session that returned to prestress levels 30-40 min post-stress. At 30 degrees C core body temperature (Tb) only decreased by 1 degree C for either swim group. Following swim, serum corticosterone (CORT) levels were significantly elevated in both escape and yoked groups in comparison to confined and home cage controls. The confined control group showed a significant elevation that was approximately halfway between the home cage control and the swim stress groups. At 30 degrees C, there was still a significant elevation of serum CORT in both swim groups in comparison to confined and home cage controls. Therefore, 30 degrees C appears to be the optimal water temperature to evaluate stress controllability effects in the current paradigm. In a final experiment, swim stressor controllability effects were examined in a 5 min forced swim test (FST) 24 h following the initial stress exposure. Rats exposed to yoked-inescapable swim stress at 30 degrees C exhibited more immobility than their escapable swim stress and confined counterparts, while the escape and confined controls did not differ. These results demonstrate that the behavioral deficits observed in the FST are attributable to the stress of inescapable swim and not swim stress per se.

Prior exposure to corticosterone markedly enhances and prolongs the neuroinflammatory response to systemic challenge with LPS

PubMed Central

Michalovicz, Lindsay T.; Miller, Julie V.; Castranova, Vincent; Miller, Diane B.

2018-01-01

Systemic exposure to the inflammagen and bacterial endotoxin lipopolysaccharide (LPS) has been widely used to evaluate inflammation and sickness behavior. While many inflammatory conditions occur in the periphery, it is well established that peripheral inflammation can affect the brain. Neuroinflammation, the elaboration of proinflammatory mediators in the CNS, commonly is associated with behavioral symptoms (e.g., lethargy, anhedonia, anorexia, depression, etc.) termed sickness behavior. Stressors have been shown to interact with and alter neuroinflammatory responses and associated behaviors. Here, we examined the effects of the stress hormone, corticosterone (CORT), as a stressor mimic, on neuroinflammation induced with a single injection (2mg/kg, s.c.) or inhalation exposure (7.5 μg/m3) of LPS or polyinosinic:polycytidylic acid (PIC; 12mg/kg, i.p.) in adult male C57BL/6J mice. CORT was given in the drinking water (200 mg/L) for 1 week or every other week for 90 days followed by LPS. Proinflammatory cytokine expression (TNFα, IL-6, CCL2, IL-1β, LIF, and OSM) was measured by qPCR. The activation of the neuroinflammation downstream signaling activator, STAT3, was assessed by immunoblot of pSTAT3Tyr705. The presence of astrogliosis was assessed by immunoassay of GFAP. Acute exposure to LPS caused brain-wide neuroinflammation without producing astrogliosis; exposure to CORT for 1 week caused marked exacerbation of the LPS-induced neuroinflammation. This neuroinflammatory “priming” by CORT was so pronounced that sub-neuroinflammatory exposures by inhalation instigated neuroinflammation when paired with prior CORT exposure. This effect also was extended to another common inflammagen, PIC (a viral mimic). Furthermore, a single week of CORT exposure maintained the potential for priming for 30 days, while intermittent exposure to CORT for up to 90 days synergistically primed the LPS-induced neuroinflammatory response. These findings highlight the possibility for an isolated inflammatory event to be exacerbated by a temporally distant stressful stimulus and demonstrates the potential for recurrent stress to greatly aggravate chronic inflammatory disorders. PMID:29304053

Acute testosterone and cortisol responses to high power resistance exercise.

PubMed

Fry, A C; Lohnes, C A

2010-01-01

This study examined the acute hormonal responses to a single high power resistance exercise training session. Four weight trained men (X +/- SD; age [yrs] = 24.5 +/- 2.9; hgt [m] = 1.82 + 0.05; BM [kg] = 96.9 +/- 10.6; I RM barbell squat [kg] = 129.3 +/- 17.4) participated as subjects in two randomly ordered sessions. During the lifting session, serum samples were collected pre- and 5 min post-exercise, and later analyzed for testosterone (Tes), cortisol (Cort), their ratio (Tes/Cort), and lactate (HLa). The lifting protocol was 10 x 5 speed squats at 70% of system mass (1 RM +/- BW) with 2 min inter-set rest intervals. Mean power and velocity were determined for each repetition using an external dynamometer. On the control day, the procedures and times (1600-1900 hrs) were identical except the subjects did not lift. Tes and Cort were analyzed via EIA. Mean +/- SD power and velocity was 1377.1 +/- 9.6 W and 0.79 +/- 0.01 m .s-1 respectively for all repetitions, and did not decrease over the 10 sets (p < 0.05). Although not significant, post-exercise Tes exhibited a very large effect size (nmol x L-1 pre = 12.5 +/- 2.9, post = 20.0 +/- 3.9; Cohen's D = 1.27). No changes were observed for either Cort or the Tes/Cort ratio. HLa significantly increased post-exercise (mmol x L-1 ; pre = 1.00 +/- 0.09, post = 4.85 +/- 1.10). The exercise protocol resulted in no significant changes in Tes, Cort or the Tes/Cort ratio, although the Cohen's D value indicates a very large effect size for the Tes response. The acute increase for Tes is in agreement with previous reports that high power activities can elicit a Tes response. High power resistance exercise protocols such as the one used in the present study produce acute increases of Tes. These results indicate that high power resistance exercise can contribute to an anabolic hormonal response with this type of training, and may partially explain the muscle hypertrophy observed in athletes who routinely employ high power resistance exercise.

Dietary supplementation of Zingiber officinale and Zingiber zerumbet to heat-stressed broiler chickens and its effect on heat shock protein 70 expression, blood parameters and body temperature.

PubMed

Hasheimi, S R; Zulkifli, I; Somchit, M N; Zunita, Z; Loh, T C; Soleimani, A F; Tang, S C

2013-08-01

The present study was conducted to assess the effects of dietary supplementation of Zingiber officinale and Zingiber zerumbet and to heat-stressed broiler chickens on heat shock protein (HSP) 70 density, plasma corticosterone concentration (CORT), heterophil to lymphocyte ratio (HLR) and body temperature. Beginning from day 28, chicks were divided into five dietary groups: (i) basal diet (control), (ii) basal diet +1%Z. zerumbet powder (ZZ1%), (iii) basal diet +2%Z. zerumbet powder (ZZ2%), (iv) basal diet +1%Z. officinale powder (ZO1%) and (v) basal diet +2%Z. officinale powder (ZO2%). From day 35-42, heat stress was induced by exposing birds to 38±1°C and 80% RH for 2 h/day. Irrespective of diet, heat challenge elevated HSP70 expression, CORT and HLR on day 42. On day 42, following heat challenge, the ZZ1% birds showed lower body temperatures than those of control, ZO1% and ZO2%. Neither CORT nor HLR was significantly affected by diet. The ZO2% and ZZ2% diets enhanced HSP70 expression when compared to the control groups. We concluded that dietary supplementation of Z. officinale and Z. zerumbet powder may induce HSP70 reaction in broiler chickens exposed to heat stress. © 2012 Blackwell Verlag GmbH.

Brain-derived neurotrophic factor heterozygous mutant rats show selective cognitive changes and vulnerability to chronic corticosterone treatment.

PubMed

Gururajan, A; Hill, R A; van den Buuse, M

2015-01-22

Brain-derived neurotrophic factor (BDNF) is a widely expressed neurotrophin involved in neurodevelopment, neuroprotection and synaptic plasticity. It is also implicated in a range of psychiatric disorders such as schizophrenia, depression and post-traumatic stress disorder. Stress during adolescence/young adulthood can have long-term psychiatric and cognitive consequences, however it is unknown how altered BDNF signaling is involved in such effects. Here we investigated whether a congenital deficit in BDNF availability in rats increases vulnerability to the long-term effects of the stress hormone, corticosterone (CORT). Compared to wildtype (WT) littermates, BDNF heterozygous (HET) rats showed higher body weights and minor developmental changes, such as reduced relative brain and pituitary weight. These animals furthermore showed deficits in short-term spatial memory in the Y-maze and in prepulse inhibition and startle, but not in object-recognition memory. CORT treatment induced impairments in novel-object recognition memory in both genotypes but disrupted fear conditioning extinction learning in BDNF HET rats only. These results show selective behavioral changes in BDNF HET rats, at baseline or after chronic CORT treatment and add to our understanding of the role of BDNF and its interaction with stress. Importantly, this study demonstrates the utility of the BDNF HET rat in investigations into the pathophysiology of various psychiatric disorders. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

The effect of water restriction on physiological and blood parameters on lactating dairy cows reared under Mediterranean climate.

PubMed

Benatallah, Amel; Ghozlane, Faissal; Marie, Michel

2018-05-31

This study was conducted to evaluate the effect of water restriction (WR) on physiological and blood parameters on lactating dairy cows reared under Mediterranean climate. The trial lasted 16 days preceded by two weeks of adaptation to the experimental condition in spring 2014 on 6 dairy cows in mid-lactation. These cows were watered at will for 4 days (W100) (hydration period), then split into 2 groups, one group has received 25% and the other 50% of water compared to their mean water consumption during the hydration period; then rehydrated for 4 days. Feed intake and physiological parameters: respiratory rate (RR), heart rate (HR) and rectal temperature (RT) were recorded twice a day. Par cons, the blood was collected once a day and analyzed for serum concentration of glucose (Glc), triglycerides (TG), cholesterol (Chol), urea (Ur), creatinine (Crea) and total protein (TP) by enzymatic colorimetric method and cortisol (Cort) by radioimmunoassay (RIA). Total dry matter intake (TDMI) was affected by WR. In fact, a decrease in TDMI was observed in WR groups compared to W100 group (effect, group, period, day, group x day, period x day: p<0.001). Also, WR resulted in a significant increase in RR, HR, RT in WR groups than in W100 group (effect, group: p<0.001). In addition, an increase in the serum concentration of Glc, TG, Chol, Ur, Crea, TP and Cort was noted in WR groups (effect, group, period, day: p<0.001) . This study has shown the ability of cows raised in a Mediterranean climate to cope with different levels of water restriction and thus reach a new equilibrium. As result, the important role of water as a limiting factor for livestock in environments with low water availability.

Wave exposure of Corte Madera Marsh, Marin County, California-a field investigation

USGS Publications Warehouse

Lacy, Jessica R.; Hoover, Daniel J.

2011-01-01

Tidal wetlands provide valuable habitat, are an important source of primary productivity, and can help to protect the shoreline from erosion by attenuating approaching waves. These functions are threatened by the loss of tidal marshes, whether due to erosion, sea-level rise, or land-use practices. Erosion protection by wetlands is expected to vary geographically, because wave attenuation in marshes depends on vegetation type, density, and height and wave attenuation over mudflats depends on slope and sediment properties. In macrotidal northern European marshes, a 50 percent reduction in wave height within tens of meters of vegetated salt marsh has been observed. This study was designed to evaluate the role of mudflats and marshes in attenuating waves at a site in San Francisco Bay. In prehistoric times, the shoreline of San Francisco Bay was ringed with tidal wetlands, with mudflats at lower elevations and marshes above. Most of the marshes around the Bay emerged 2,000-4,000 years ago, after the rate of sea-level rise slowed to approximately 1 mm/year. Approximately 80 percent of the acreage of tidal marsh and 40 percent of the acreage of tidal mudflats in San Francisco Bay have been lost to filling and draining since 1800. Tidal wetlands are particularly susceptible to impacts from sea-level rise because the vegetation at each elevation is adapted to a specific tidal-inundation regime. The maintenance of suitable marsh-plain elevations depends on a supply of sediment that can keep up with the rate of sea-level rise. Sea-level rise, which according to recent projections may reach 75 to 190 cm by the year 2100, poses a significant threat to wetlands in San Francisco Bay, where landward migration is frequently impossible due to urbanization of the adjacent landscape. In this study, we collected data in Corte Madera Bay and Marsh to determine whether, and to what degree, waves are attenuated as they transit the Bay and, during high tides, the marsh. Corte Madera Bay was selected as a study site because of its exposure to wind waves, as well as its history of shoreline erosion and marsh restoration and monitoring. Data were collected in the winter of 2010, along a cross-shore transect extending from offshore of the subtidal mudflats into the tidal marsh. This study forms part of the Innovative Wetland Adaptation in the Lower Corte Madera Creek Watershed Project initiated by the Bay Conservation and Development Commission (BCDC) (http://www.bcdc.ca.gov/planning/climate_change/WetlandAdapt.shtml). Objectives- This study was designed to address the following questions: * What are the characteristics of waves and currents in the study area, and how do they vary over time? * Do wave heights or orbital velocities decrease, or wave periods change, as waves pass over the mudflats? * Do wave heights decrease, or wave periods change, as waves pass over the marsh?

Combined treatment with corticosteroids and moclobemide favors normalization of hypothalamo-pituitary-adrenal axis dysregulation in relapsing-remitting multiple sclerosis: a randomized, double blind trial.

PubMed

Then Bergh, F; Kümpfel, T; Grasser, A; Rupprecht, R; Holsboer, F; Trenkwalder, C

2001-04-01

Hyperresponsiveness of the hypothalamo-pituitary-adrenal (HPA) axis in multiple sclerosis (MS), an autoimmune inflammatory disease of the central nervous system, is presumably due to diminished corticosteroid receptor function. It probably influences the immune response, but its clinical significance is not clear. Similar HPA dysregulation occurs in depression and is reversible with successful antidepressant treatment. We conducted a double blind, placebo-controlled trial to evaluate the neuroendocrine effect of cotreatment with the antidepressant moclobemide as an adjunct to oral corticosteroids in MS. Twenty-one patients with definite relapsing-remitting MS (11 females, aged 33.9 +/- 2.0 yr; Expanded Disability Status Scale score of neurological impairment, 2.0--6.5) in acute relapse were treated with placebo (n = 13) or 300 mg moclobemide (reversible monoamine oxidase A inhibitor; n = 8) for 75 days. All received oral fluocortolone from day 7 on, and the dose was tapered until day 29. Effects were evaluated using the combined dexamethasone-CRH test and clinically on days 1, 30, and 75. At baseline, the HPA axis was mildly activated, comparably for treatment groups [area under the curve for cortisol (AUC-Cort), 213.8 +/- 76.8 arbitrary units in the moclobemide group vs. 225.8 +/- 65.1 in the steroid alone group; mean +/- SEM]. In a group of healthy controls with comparable demographic characteristics, the AUC-Cort was 107.4 +/- 14.1. Moclobemide cotreatment resulted in normalization of the HPA axis response, whereas the HPA system hyperresponse was maintained with steroids alone (AUC-Cort on day 30, 85.9 +/- 22.8 vs.177.1 +/- 68.5; on day 75, 111.0 +/- 46.0 vs. 199.2 +/- 64.6). The change in Expanded Disability Status Scale was comparable for both groups. Although corticosteroids alone had no effect on the HPA response using the dexamethasone-CRH test, treatment with moclobemide combined with corticosteroids favors normalization of the HPA response in relapsing-remitting MS.

JIEYUANSHEN DECOCTION EXERTS ANTIDEPRESSANT EFFECTS ON DEPRESSIVE RAT MODEL VIA REGULATING HPA AXIS AND THE LEVEL OF AMINO ACIDS NEUROTRANSMITTER

PubMed Central

qiuxia, Zhang; xinlong, Ma; yilong, Yang; hui, Zhao; yali, Wang; xiaoquan, Yao; lei, Wang; jiahui, Chang; haiyan, Zou

2017-01-01

Background: Jieyuanshen decoction (JYAS-D) - a traditional Chinese medicine was invented by Professor Nie based on classic formulas, chaihu jia longgu muli decoction has been proved as having favorable curative effects on depression in clinical practices. The aim of this study was to investigate the antidepressant effects and its molecular mechanism of JYAS-D. Materials and Methods: The model of depression was established by Chronic Unpredictable Stress. Different doses (8.2 g/kg, 16.3 g/kg, 32.7 g/kg) of JYAS-D was orally administered; Fluoxetine was orally administered with 10mg/kg. All treatments lasted for 28 days. Sucrose preference and open-field tests were adopted to observe the behavior of rats. OPA (ortho-phthalaldehyde) derivatization method was used to detect the contents of amino acid neurotransmitter. RIA (Radiation immunity analysis) method was used to measure the serum concentrations of CORT (Corticosterone), ACTH (Adrenocorticotropic hormone) and CRH (Corticotropin-releasing hormone). ELISA (Enzyme linked immunosorbent assay) method was adopted to examine the contents of Glucocorticoid receptor (GR) and Mineralocorticoid receptor (MR) in hippocampus. Results: Compared with the model group, sucrose preference was increased in all treatment groups. The concentration of serum CORT was reduced in the middle dose of JYAS-D and control groups; the concentration of serum ACTH was reduced in the low and high-dose of JYAS-D; the concentration of serum CRH was reduced in the middle and high-dose of JYAS-D. The content of hippocampus GR was increased in the middle and high-dose of JYAS-D; the content of hippocampus Glu (Glutamic acid) was reduced among the low, middle and high-dose of JYAS-D and fluoxetine group, the ratio of Glu/γ-GABA (y-aminobutyric acid was reduced in the low and high-dose of JYAS-D. Conclusion: JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter. PMID:28573220

JIEYUANSHEN DECOCTION EXERTS ANTIDEPRESSANT EFFECTS ON DEPRESSIVE RAT MODEL VIA REGULATING HPA AXIS AND THE LEVEL OF AMINO ACIDS NEUROTRANSMITTER.

PubMed

Qiuxia, Zhang; Xinlong, Ma; Yilong, Yang; Hui, Zhao; Yali, Wang; Xiaoquan, Yao; Lei, Wang; Jiahui, Chang; Haiyan, Zou

2017-01-01

Jieyuanshen decoction (JYAS-D) - a traditional Chinese medicine was invented by Professor Nie based on classic formulas, chaihu jia longgu muli decoction has been proved as having favorable curative effects on depression in clinical practices. The aim of this study was to investigate the antidepressant effects and its molecular mechanism of JYAS-D. The model of depression was established by Chronic Unpredictable Stress. Different doses (8.2 g/kg, 16.3 g/kg, 32.7 g/kg) of JYAS-D was orally administered; Fluoxetine was orally administered with 10mg/kg. All treatments lasted for 28 days. Sucrose preference and open-field tests were adopted to observe the behavior of rats. OPA (ortho-phthalaldehyde) derivatization method was used to detect the contents of amino acid neurotransmitter. RIA (Radiation immunity analysis) method was used to measure the serum concentrations of CORT (Corticosterone), ACTH (Adrenocorticotropic hormone) and CRH (Corticotropin-releasing hormone). ELISA (Enzyme linked immunosorbent assay) method was adopted to examine the contents of Glucocorticoid receptor (GR) and Mineralocorticoid receptor (MR) in hippocampus. Compared with the model group, sucrose preference was increased in all treatment groups. The concentration of serum CORT was reduced in the middle dose of JYAS-D and control groups; the concentration of serum ACTH was reduced in the low and high-dose of JYAS-D; the concentration of serum CRH was reduced in the middle and high-dose of JYAS-D. The content of hippocampus GR was increased in the middle and high-dose of JYAS-D; the content of hippocampus Glu (Glutamic acid) was reduced among the low, middle and high-dose of JYAS-D and fluoxetine group, the ratio of Glu/γ-GABA (y-aminobutyric acid was reduced in the low and high-dose of JYAS-D. JYAS-D had a significant antidepressant-like effect on rat model through regulating serum concentration of CORT, ACTH and CRH, increasing the content of hippocampus GR and regulating the equilibrium of amino acids neurotransmitter.

Sex-specific differences in corticosterone secretion, behavioral phenotypes and expression of TrkB.T1 and TrkB.FL receptor isoforms: Impact of systemic TrkB inhibition and combinatory stress exposure in adolescence.

PubMed

Azogu, Idu; Liang, Jacky; Plamondon, Helene

2018-05-09

Stress exposure has been implicated in the development of mood disorders, although little is known about the lasting effects of repeated stress during the adolescent period on sex-specific differences in endocrine and plasticity-signaling responses in adulthood. Using a 10-day combinatory stress paradigm (postnatal day (PND) 26 to 35), we examined sex-specific impact of adolescent stress and inhibition of tyrosine-related kinase B (TrkB) receptor (ANA-12; 0.5 mg/kg, i.p.) on 1) adolescent blood corticosterone levels, 2) adult locomotion and anxiety-like behavior, and 3) region-specific differences in endogenous TrkB full-length (TrkB.FL) and truncated (TrkB.T1) receptor isoforms. Blood collected on days 1, 5 and 10 revealed elevated basal and stress-induced CORT secretion in females compared to males, while ANA-12 attenuated CORT elevations post stress in both sexes. As adults, all females exhibited higher locomotor and exploratory activity than males in the open field test and elevated plus maze, and differences were comparable in the forced swim within stress-naïve and stress groups. Biochemically, vehicle-treated males showed elevated TrkB.T1 and TrkB.FL compared to vehicle-treated females in the PFC, hippocampus and NAc, and levels were consistently attenuated by ANA-12 treatment in non-stress males. With regards to stress exposure, expression of both isoforms was strongly down-regulated in the NAc of males only and was associated with increased TrkB.T1 in the PFC. ANA-12 enhanced expression in females, independent of stress exposure, compared to vehicle-treated counterparts, expression being increased for TrkB.T1 versus TrkB.FL and magnitude of the changes being region-specific. In contrast, ANA-12 effects in stressed males were restricted to inhibition of both isoforms in the hippocampus. Together, our findings support that TrkB activation, contingent on stress exposure, differentially affects TrkB isoform regulation during adulthood. Sex-specific biochemical responses at delayed intervals following adolescent stress exposure further support the need to include the sex variable in animal models. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

Choir versus Solo Singing: Effects on Mood, and Salivary Oxytocin and Cortisol Concentrations

PubMed Central

Schladt, T. Moritz; Nordmann, Gregory C.; Emilius, Roman; Kudielka, Brigitte M.; de Jong, Trynke R.; Neumann, Inga D.

2017-01-01

The quantification of salivary oxytocin (OXT) concentrations emerges as a helpful tool to assess peripheral OXT secretion at baseline and after various challenges in healthy and clinical populations. Both positive social interactions and stress are known to induce OXT secretion, but the relative influence of either of these triggers is not well delineated. Choir singing is an activity known to improve mood and to induce feelings of social closeness, and may therefore be used to investigate the effects of positive social experiences on OXT system activity. We quantified mood and salivary OXT and cortisol (CORT) concentrations before, during, and after both choir and solo singing performed in a randomized order in the same participants (repeated measures). Happiness was increased, and worry and sadness as well as salivary CORT concentrations were reduced, after both choir and solo singing. Surprisingly, salivary OXT concentrations were significantly reduced after choir singing, but did not change in response to solo singing. Salivary OXT concentrations showed high intra-individual stability, whereas salivary CORT concentrations fluctuated between days within participants. The present data indicate that the social experience of choir singing does not induce peripheral OXT secretion, as indicated by unchanged salivary OXT levels. Rather, the reduction of stress/arousal experienced during choir singing may lead to an inhibition of peripheral OXT secretion. These data are important for the interpretation of future reports on salivary OXT concentrations, and emphasize the need to strictly control for stress/arousal when designing similar experiments. PMID:28959197

Choir versus Solo Singing: Effects on Mood, and Salivary Oxytocin and Cortisol Concentrations.

PubMed

Schladt, T Moritz; Nordmann, Gregory C; Emilius, Roman; Kudielka, Brigitte M; de Jong, Trynke R; Neumann, Inga D

2017-01-01

The quantification of salivary oxytocin (OXT) concentrations emerges as a helpful tool to assess peripheral OXT secretion at baseline and after various challenges in healthy and clinical populations. Both positive social interactions and stress are known to induce OXT secretion, but the relative influence of either of these triggers is not well delineated. Choir singing is an activity known to improve mood and to induce feelings of social closeness, and may therefore be used to investigate the effects of positive social experiences on OXT system activity. We quantified mood and salivary OXT and cortisol (CORT) concentrations before, during, and after both choir and solo singing performed in a randomized order in the same participants (repeated measures). Happiness was increased, and worry and sadness as well as salivary CORT concentrations were reduced, after both choir and solo singing. Surprisingly, salivary OXT concentrations were significantly reduced after choir singing, but did not change in response to solo singing. Salivary OXT concentrations showed high intra-individual stability, whereas salivary CORT concentrations fluctuated between days within participants. The present data indicate that the social experience of choir singing does not induce peripheral OXT secretion, as indicated by unchanged salivary OXT levels. Rather, the reduction of stress/arousal experienced during choir singing may lead to an inhibition of peripheral OXT secretion. These data are important for the interpretation of future reports on salivary OXT concentrations, and emphasize the need to strictly control for stress/arousal when designing similar experiments.

Plasma cortisol and noradrenalin concentrations in pigs: automated sampling of freely moving pigs housed in PigTurn versus manually sampled and restrained pigs

USDA-ARS?s Scientific Manuscript database

Minimizing the effects of restraint and human interaction on the endocrine physiology of animals is essential for collection of accurate physiological measurements. Our objective was to compare stress-induced cortisol (CORT) and noradrenalin (NorA) responses in automated versus manual blood sampling...

GLUCOCORTICOIDS REGULATE THE SYNTHESIS OF GFAP IN INTACT AND ADRENALECTOMIZED RATS BUT DO NOT AFFECT ITS EXPRESSION FOLLOWING BRAIN INJURY

EPA Science Inventory

We examined the effects of corticosterone (CORT) on the amount of glial fibrillary acidic protein (GFAP) in INTACT, adrenalectomized (ADX) and brain-damaged rats. hort (5 days)- to long-term (4 months) CORT administration by injection, pellet implantation, or in the drinking wate...

Dietary Selenomethionine Administration and Its Effects on the American Alligator (Alligator mississippiensis): Oxidative Status and Corticosterone Levels.

PubMed

Finger, John W; Hamilton, Matthew T; Kelley, Meghan D; Zhang, Yufeng; Kavazis, Andreas N; Glenn, Travis C; Tuberville, Tracey D

2018-07-01

Selenium (Se) is an essential nutrient which in excess causes toxicity. The disposal of incompletely combusted coal, which often is rich in Se, into aquatic settling basins is increasing the risk of Se exposure worldwide. However, very few studies have looked at the physiological effects of Se exposure on long-lived, top trophic vertebrates, such as the American alligator (Alligator mississippiensis). During a 7-week period, alligators were fed one of three dietary treatments: mice injected with deionized water or mice injected with water containing 1000 or 2000 ppm selenomethionine (SeMet). One week after the last feeding alligators were bled within 3 min of capture for plasma corticosterone (CORT). A few days later, all alligators were euthanized and whole blood and tail tissue were harvested to measure oxidative damage, an antioxidant-associated transcription factor, and antioxidant enzymes [glutathione peroxidase-1 (GPX1), superoxide dismutase-1 (SOD1), and SOD2] by Western blotting. There was a dose-dependent increase in baseline CORT levels in alligators administered SeMet. Except for blood SOD2 levels, SeMet treatment had no effect (p > 0.05 for all) on oxidative status: oxidative damage, GPX1, SOD1, and muscle SOD2 levels were similar among treatments. Our results illustrate that high levels of Se may act as a stressor to crocodilians. Future studies should investigate further the physiological effects of Se accumulation in long-lived, top-trophic vertebrates.

High-dose corticosterone after fear conditioning selectively suppresses fear renewal by reducing anxiety-like response.

PubMed

Wang, Hongbo; Xing, Xiaoli; Liang, Jing; Bai, Yunjing; Lui, Zhengkui; Zheng, Xigeng

2014-09-01

Exposure therapy is widely used to treat anxiety disorders, including posttraumatic stress disorder (PTSD). However, preventing the return of fear is still a major challenge after this behavioral treatment. An increasing number of studies suggest that high-dose glucocorticoid treatment immediately after trauma can alleviate the symptoms of PTSD in humans. Unknown is whether high-dose glucocorticoid treatment following fear conditioning suppresses the return of fear. In the present study, a typical fear renewal paradigm (AAB) was used, in which the fear response to an auditory cue can be restored in a novel context (context B) when both training and extinction occur in the same context (context A). We trained rats for auditory fear conditioning and administered corticosterone (CORT; 5 and 25mg/kg, i.p.) or vehicle with different delays (1 and 24h). Forty-eight hours after drug injection, extinction was conducted with no drug in the training context, followed by a test of tone-induced freezing behavior in the same (AAA) or a shifted (AAB) context. Both immediate and delayed administration of high-dose CORT after fear conditioning reduced fear renewal. To examine the anxiolytic effect of CORT, independent rats were trained for cued or contextual fear conditioning, followed by an injection of CORT (5 and 25mg/kg, i.p.) or vehicle at a 1 or 24h delay. One week later, anxiety-like behavior was assessed in the elevated plus maze (EPM) before and after fear expression. We found that high-dose CORT decreased anxiety-like behavior without changing tone- or context-induced freezing. These findings indicate that a single high-dose CORT administration given after fear conditioning may selectively suppress fear renewal by reducing anxiety-like behavior and not by altering the consolidation, retrieval, or extinction of fear memory. Copyright © 2014 Elsevier Inc. All rights reserved.

11β-Hydroxysteroid dehydrogenase type 1 shRNA ameliorates glucocorticoid-induced insulin resistance and lipolysis in mouse abdominal adipose tissue.

PubMed

Wang, Ying; Yan, Chaoying; Liu, Limei; Wang, Wei; Du, Hanze; Fan, Winnie; Lutfy, Kabirullah; Jiang, Meisheng; Friedman, Theodore C; Liu, Yanjun

2015-01-01

Long-term glucocorticoid exposure increases the risk for developing type 2 diabetes. Prereceptor activation of glucocorticoid availability in target tissue by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) coupled with hexose-6-phosphate dehydrogenase (H6PDH) is an important mediator of the metabolic syndrome. We explored whether the tissue-specific modulation of 11β-HSD1 and H6PDH in adipose tissue mediates glucocorticoid-induced insulin resistance and lipolysis and analyzed the effects of 11β-HSD1 inhibition on the key lipid metabolism genes and insulin-signaling cascade. We observed that corticosterone (CORT) treatment increased expression of 11β-HSD1 and H6PDH and induced lipase HSL and ATGL with suppression of p-Thr(172) AMPK in adipose tissue of C57BL/6J mice. In contrast, CORT induced adipose insulin resistance, as reflected by a marked decrease in IR and IRS-1 gene expression with a reduction in p-Thr(308) Akt/PKB. Furthermore, 11β-HSD1 shRNA attenuated CORT-induced 11β-HSD1 and lipase expression and improved insulin sensitivity with a concomitant stimulation of pThr(308) Akt/PKB and p-Thr(172) AMPK within adipose tissue. Addition of CORT to 3T3-L1 adipocytes enhanced 11β-HSD1 and H6PDH and impaired p-Thr(308) Akt/PKB, leading to lipolysis. Knockdown of 11β-HSD1 by shRNA attenuated CORT-induced lipolysis and reversed CORT-mediated inhibition of pThr(172) AMPK, which was accompanied by a parallel improvement of insulin signaling response in these cells. These findings suggest that elevated adipose 11β-HSD1 expression may contribute to glucocorticoid-induced insulin resistance and adipolysis. Copyright © 2015 the American Physiological Society.

78 FR 22620 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-16

...''), Col Bella Vista, Casa No. 09, Camino a Rotulo de Coca Cola, San Pedro Sula, Cortes, Honduras; DOB 14...] (Linked To: AUTO PARTES HANDAL S. DE R.L. DE C.V.; Linked To: RANCHO LA HERRADURA; Linked To: SUPERTIENDAS..., La Ceiba, Atlantida, Honduras; Ave Junior, Entre 7 y 6 Calle Sureste, San Pedero Sula, Cortes...

IGF-II promotes neuroprotection and neuroplasticity recovery in a long-lasting model of oxidative damage induced by glucocorticoids.

PubMed

Martín-Montañez, E; Millon, C; Boraldi, F; Garcia-Guirado, F; Pedraza, C; Lara, E; Santin, L J; Pavia, J; Garcia-Fernandez, M

2017-10-01

Insulin-like growth factor-II (IGF-II) is a naturally occurring hormone that exerts neurotrophic and neuroprotective properties in a wide range of neurodegenerative diseases and ageing. Accumulating evidence suggests that the effects of IGF-II in the brain may be explained by its binding to the specific transmembrane receptor, IGFII/M6P receptor (IGF-IIR). However, relatively little is known regarding the role of IGF-II through IGF-IIR in neuroprotection. Here, using adult cortical neuronal cultures, we investigated whether IGF-II exhibits long-term antioxidant effects and neuroprotection at the synaptic level after oxidative damage induced by high and transient levels of corticosterone (CORT). Furthermore, the involvement of the IGF-IIR was also studied to elucidate its role in the neuroprotective actions of IGF-II. We found that neurons treated with IGF-II after CORT incubation showed reduced oxidative stress damage and recovered antioxidant status (normalized total antioxidant status, lipid hydroperoxides and NAD(P) H:quinone oxidoreductase activity). Similar results were obtained when mitochondria function was analysed (cytochrome c oxidase activity, mitochondrial membrane potential and subcellular mitochondrial distribution). Furthermore, neuronal impairment and degeneration were also assessed (synaptophysin and PSD-95 expression, presynaptic function and FluoroJade B® stain). IGF-II was also able to recover the long-lasting neuronal cell damage. Finally, the effects of IGF-II were not blocked by an IGF-IR antagonist, suggesting the involvement of IGF-IIR. Altogether these results suggest that, in or model, IGF-II through IGF-IIR is able to revert the oxidative damage induced by CORT. In accordance with the neuroprotective role of the IGF-II/IGF-IIR reported in our study, pharmacotherapy approaches targeting this pathway may be useful for the treatment of diseases associated with cognitive deficits (i.e., neurodegenerative disorders, depression, etc.). Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Topical 11β-Hydroxysteroid Dehydrogenase Type 1 Inhibition Corrects Cutaneous Features of Systemic Glucocorticoid Excess in Female Mice.

PubMed

Tiganescu, Ana; Hupe, Melanie; Uchida, Yoshikazu; Mauro, Theadora; Elias, Peter M; Holleran, Walter M

2018-01-01

Glucocorticoid (GC) excess drives multiple cutaneous adverse effects, including skin thinning and poor wound healing. The ubiquitously expressed enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) activates mouse corticosterone from 11-dehydrocorticosterone (and human cortisol from cortisone). We previously demonstrated elevated 11β-HSD1 activity during mouse wound healing, but the interplay between cutaneous 11β-HSD1 and systemic GC excess is unexplored. Here, we examined effects of 11β-HSD1 inhibition by carbenoxolone (CBX) in mice treated with corticosterone (CORT) or vehicle for 6 weeks. Mice were treated bidaily with topical CBX or vehicle (VEH) 7 days before wounding and during wound healing. CORT mice displayed skin thinning and impaired wound healing but also increased epidermal integrity. 11β-HSD1 activity was elevated in unwounded CORT skin and was inhibited by CBX. CORT mice treated with CBX displayed 51%, 59%, and 100% normalization of wound healing, epidermal thickness, and epidermal integrity, respectively. Gene expression studies revealed normalization of interleukin 6, keratinocyte growth factor, collagen 1, collagen 3, matrix metalloproteinase 9, and tissue inhibitor of matrix metalloproteinase 4 by CBX during wound healing. Importantly, proinflammatory cytokine expression and resolution of inflammation were unaffected by 11β-HSD1 inhibition. CBX did not regulate skin function or wound healing in the absence of CORT. Our findings demonstrate that 11β-HSD1 inhibition can limit the cutaneous effects of GC excess, which may improve the safety profile of systemic steroids and the prognosis of chronic wounds. Copyright © 2018 Endocrine Society.

Educational Facility Evaluations of Primary Schools in Rural Honduras: Departments of Cortes and Meambar.

ERIC Educational Resources Information Center

Council of Educational Facility Planners, International, Scottsdale, AZ.

A team of 11 educational facility planners and architects from the United States and Canada conducted a facility evaluation of schools in the rural areas of Meambar and Cortes, Honduras. Team members were all part of the Council of Educational Facility Planners, International and traveled to Honduras under the auspices of a Christian mission…

Christopher Columbus, Hernando Cortes, and Francisco Pizzaro: A Qualitative Content Analysis Examining Cultural Bias in World History Textbooks

ERIC Educational Resources Information Center

Lillejord, Jebadiah Serril

2013-01-01

The purpose of this study is to investigate to what extent contemporary high school world history textbooks portray Christopher Columbus, Hernán Cortés, and Francisco Pizarro within the context of being "sacred," "profane," or someplace in between. To evaluate for existence of content bias this study employed qualitative…

Activation of mGluR2/3 following stress hormone exposure restores sensitivity to alcohol in rats.

PubMed

Jaramillo, Anel A; Randall, Patrick A; Frisbee, Suzanne; Fisher, Kristen R; Besheer, Joyce

2015-09-01

Sensitivity to the interoceptive effects of alcohol is blunted following a period of exposure to the stress hormone corticosterone (CORT), an effect that is suggested to be related, in part, to glutamatergic neuroadaptations. Group II metabotropic glutamate receptors (subtypes 2 and 3; mGluR2/3) modulate several drug- and alcohol-related behaviors, including the interoceptive (discriminative stimulus) effects of alcohol. Therefore, we sought to determine if manipulation of mGluR2/3 would restore sensitivity to the interoceptive effects of alcohol following CORT exposure. Using a two-lever drug discrimination task, male Long-Evans rats were trained to discriminate alcohol (1 g/kg, intragastric [IG]) vs. water. First, the effect of mGluR2/3 antagonism on the discriminative stimulus effects of alcohol was determined using LY341495 (0.3-3.0 mg/kg; intraperitoneal [IP]). Next, the effects of mGluR2/3 antagonism and activation were assessed in discrimination-trained animals exposed to CORT (300 μg/mL) in the home cage drinking water or water only, for 7 days. Following CORT exposure, decreased sensitivity to alcohol (1 g/kg) was observed. Pretreatment with the mGluR2/3 agonist LY379268 (1.0-3.0 mg/kg; IP), but not the mGluR2/3 antagonist (0.3-1.0 mg/kg; IP), restored sensitivity to alcohol. Additionally, in water controls, mGluR2/3 antagonism and mGluR2/3 activation disrupted expression of the discriminative stimulus effects of alcohol. Together, these findings suggest that blunted sensitivity to the interoceptive effects of alcohol following an episode of heightened stress hormone levels may be due to adaptations in mGluR2/3-related systems. The ability of mGluR2/3 activation to restore sensitivity to alcohol under these conditions lends further support for the importance of these receptors under stress-related conditions. Copyright © 2015 Elsevier Inc. All rights reserved.

Different activation of ACTH and corticosterone release in response to various stressors in rats.

PubMed

Djordjević, J; Cvijić, G; Davidović, V

2003-01-01

The aim of this study was to investigate the reaction of the hypothalamo-pituitary-adrenocortical (HPA) system to various stressors (fasting, crowding, cold and heat) by measuring blood ACTH and corticosterone (CORT) concentration as well as the cholesterol (CHOL) content in the adrenals. To examine the effects of stress termination, the rats were returned and kept under control conditions for the same period as that of stress duration (supposed recovery period). According to our results HPA system was activated by all the stressors applied. Heat seems to be the strongest stressor since the exposure of animals to a high ambient temperature resulted in the greatest rise of plasma ACTH concentration as well as CORT synthesis and secretion. These values remained elevated after the stress termination i.e. after the rats had been returned to room temperature. Fasting seems to be the weakest stressor given because it causes the smallest increase in blood ACTH and CORT concentrations. Moreover, in refed rats the HPA function was fully recovered. In conclusion, the various stressors applied seem to induce a different response of the HPA system as judged by quantitative changes in ACTH and CORT release.

Antidepressant-Like Effects of Vaccinium bracteatum in Chronic Restraint Stress Mice: Functional Actions and Mechanism Explorations.

PubMed

Oh, Dool-Ri; Kim, Yujin; Choi, Eun-Jin; Jung, Myung-A; Oh, Kyo-Nyeo; Hong, Ji-Ae; Bae, Donghyuck; Kim, Kwangsu; Kang, Huwon; Kim, Jaeyong; Kim, Young Ran; Cho, Seung Sik; Choi, Chul-Young

2018-01-01

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT[Formula: see text] receptor by inhibiting 5-HT-induced intracellular Ca[Formula: see text] and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT[Formula: see text] receptor.

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms.

PubMed

Huang, Hegui; He, Zheng; Zhu, Chunyan; Liu, Lian; Kou, Hao; Shen, Lang; Wang, Hui

2015-10-01

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observed in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a "two-programming" mechanism for PEE-induced adrenal developmental toxicity: "the first programming" is a lower functional programming of adrenal steroidogenesis, and "the second programming" is GC-metabolic activation system-related GC-IGF1 axis programming. Copyright © 2015 Elsevier Inc. All rights reserved.

Sex- and concentration-dependent effects of predator feces on seasonal regulation of body mass in the bank vole Clethrionomys glareolus.

PubMed

Tidhar, Wendy L; Bonier, Frances; Speakman, John R

2007-11-01

Increased perception of predation risk can cause changes in activity, feeding and reproductive behavior in a wide range of taxa. Many small mammals in the temperate zone exhibit fluctuations in body mass in response to changing photoperiod. Bank voles lose body mass in winter which they regain when photoperiod increases in the spring. To determine if predation risk affects seasonal changes in body mass (BM), bank voles were exposed to two concentrations (low: LC and high: HC) of weasel feces. Food intake (FI) and daily energy expenditure (DEE) were measured to establish if differences in body mass were due to adjustment in energy intake or expenditure. Fecal corticosterone (CORT) was measured to assess whether the voles had detected and responded to predator feces as a physiological stressor. Voles of both sexes had higher levels of fecal CORT in the groups exposed to weasel feces compared to controls. Voles responded to the predator feces in a sex- and concentration-dependent manner. Males responded to LC feces by gaining less mass following the change in photoperiod. This was mediated by reduced FI and higher DEE. Female voles also gained less BM in response to HC feces, but increased both FI and DEE. We hypothesize that males may gain a short-term advantage by lowering BM in response to predation risk, which may be regained without affecting reproductive success. The consequences of mass loss in females may be more significant as this may delay the onset of breeding or reduce the size or number of young, thereby negatively affecting breeding success.

Neuroactive steroids modulate HPA axis activity and cerebral brain-derived neurotrophic factor (BDNF) protein levels in adult male rats.

PubMed

Naert, Gaëlle; Maurice, Tangui; Tapia-Arancibia, Lucia; Givalois, Laurent

2007-01-01

Depression is characterized by hypothalamo-pituitary-adrenocortical (HPA) axis hyperactivity. In this major mood disorder, neurosteroids and neurotrophins, particularly brain-derived neurotrophic factor (BDNF), seem to be implicated and have some antidepressant effects. BDNF is highly involved in regulation of the HPA axis, whereas neurosteroids effects have never been clearly established. In this systematic in vivo study, we showed that the principal neuroactive steroids, namely dehydroepiandrosterone (DHEA), pregnenolone (PREG) and their sulfate esters (DHEA-S and PREG-S), along with allopregnanolone (ALLO), stimulated HPA axis activity, while also modulating central BDNF contents. In detail, DHEA, DHEA-S, PREG, PREG-S and ALLO induced corticotropin-releasing hormone (CRH) and/or arginine vasopressin (AVP) synthesis and release at the hypothalamic level, thus enhancing plasma adrenocorticotropin hormone (ACTH) and corticosterone (CORT) concentrations. This stimulation of the HPA axis occurred concomitantly with BDNF modifications at the hippocampus, amygdala and hypothalamus levels. We showed that these neurosteroids induced rapid effects, probably via neurotransmitter receptors and delayed effects perhaps after metabolization in other neuroactive steroids. We highlighted that they had peripheral effects directly at the adrenal level by inducing CORT release, certainly after estrogenic metabolization. In addition, we showed that, at the dose used, only DHEA, DHEA-S and PREG-S had antidepressant effects. In conclusion, these results highly suggest that part of the HPA axis and antidepressant effects of neuroactive steroids could be mediated by BDNF, particularly at the amygdala level. They also suggest that neurosteroids effects on central BDNF could partially explain the trophic properties of these molecules.

Nutraceuticals to promote neuronal plasticity in response to corticosterone-induced stress in human neuroblastoma cells.

PubMed

Gite, Snehal; Ross, R Paul; Kirke, Dara; Guihéneuf, Freddy; Aussant, Justine; Stengel, Dagmar B; Dinan, Timothy G; Cryan, John F; Stanton, Catherine

2018-01-29

To search for novel compounds that will protect neuronal cells under stressed conditions that may help to restore neuronal plasticity. A model of corticosterone (CORT)-induced stress in human neuroblastoma cells (SH-SY5Y) was used to compare the efficacy of 6 crude extracts and 10 pure compounds (6 polyphenols, 2 carotenoids, 1 amino acid analogue, and 1 known antidepressant drug) to increase neuronal plasticity and to decrease cytotoxicity. Astaxanthin (among pure compounds) and phlorotannin extract of Fucus vesiculosus (among crude extracts) showed a maximum increase in cell viability in the presence of excess CORT. BDNF-VI mRNA expression in SH-SY5Y cells was significantly improved by pretreatment with quercetine, astaxanthin, curcumin, fisetin, and resveratrol. Among crude extracts, xanthohumol, phlorotannin extract (Ecklonia cava), petroleum ether extract (Nannochloropsis oculata), and phlorotannin extract (F. vesiculosus) showed a significant increase in BDNF-VI mRNA expression. CREB1 mRNA expression was significantly improved by astaxanthin, β-carotene, curcumin, and fluoxetine whereas none of the crude extracts caused significant improvement. As an adjunct of fluoxetine, phlorotannin extract (F. vesiculosus), β-carotene, and xanthohumol have resulted in significant improvement in BDNF-VI mRNA expression and CREB1 mRNA expression was significantly improved by phlorotannin extract (F. vesiculosus). Significant improvement in mature BDNF protein expression by phlorotannin extract (F. vesiculosus) and β-carotene as an adjunct of fluoxetine confirm their potential to promote neuronal plasticity against CORT-induced stress. The carotenoids, flavonoids, namely quercetine, curcumin, and low molecular weight phlorotannin-enriched extract of F. vesiculosus may serve as potential neuroprotective agents promoting neuronal plasticity in vitro. Graphical abstract: Cascade of events associated with disturbed homeostatic balance of glucocorticoids and impact of phlorotannin extract (F. vesiculosus) and β-carotene in restoring neuronal plasticity. Abbreviation: TrKB, tropomyosin receptor kinase B; P-ERK, phosphorylated extracellular signal-related kinase; PI3K, phosphatidylinositol 3-kinase; Akt, protein kinase B; Ca++/CaMK, calcium/calmodulin-dependent protein kinase; pCREB, phosphorylated cAMP response element-binding protein; CRE, cAMP response elements, CORT, corticosterone; and BDNF; brain-derived neurotrophic factor.

Photography and Neobaroque Imaginary in Julio Cortázar's "Las babas del diablo": Can the Neobaroque Name a Photograph?

ERIC Educational Resources Information Center

Hakobyan, Liana

2018-01-01

This article examines Julio Cortázar's short story "Las babas del diablo" from a visual perspective and at the intersection of Roland Barthes's ideas on photography and Severo Sarduy's theory on the Neobaroque. I propose that in "Las babas del diablo" photography and the Neobaroque--two seemingly unrelated concepts--interact…

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice.

PubMed

Rompala, Gregory R; Finegersh, Andrey; Homanics, Gregg E

2016-06-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol-drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. Copyright © 2016 Elsevier Inc. All rights reserved.

Paternal preconception ethanol exposure blunts hypothalamic-pituitary-adrenal axis responsivity and stress-induced excessive fluid intake in male mice

PubMed Central

Rompala, Gregory R.; Finegersh, Andrey; Homanics, Gregg E.

2016-01-01

A growing number of environmental insults have been shown to induce epigenetic effects that persist across generations. For instance, paternal preconception exposures to ethanol or stress have independently been shown to exert such intergenerational effects. Since ethanol exposure is a physiological stressor that activates the hypothalamic-pituitary-adrenal (HPA) axis, we hypothesized that paternal ethanol exposure would impact stress responsivity of offspring. Adult male mice were exposed to chronic intermittent vapor ethanol or control conditions for 5 weeks before being mated with ethanol-naïve females to produce ethanol (E)- and control (C)-sired offspring. Adult male and female offspring were tested for plasma corticosterone (CORT) levels following acute restraint stress and the male offspring were further examined for stress-evoked 2-bottle choice ethanol drinking. Paternal ethanol exposure blunted plasma CORT levels following acute restraint stress selectively in male offspring; females were unaffected. In a stress-evoked ethanol-drinking assay, there was no effect of stress on ethanol consumption. However, C-sired males exhibited increased total fluid intake (polydipsia) in response to stress while E-sired males were resistant to this stress-induced phenotype. Taken together, these data suggest that paternal ethanol exposure imparts stress hyporesponsivity to male offspring. PMID:27286933

Calorie restriction and corticosterone elevation during lactation can each modulate adult male fear and anxiety-like behaviour.

PubMed

Govic, Antonina; Bell, Veronica; Samuel, Anil; Penman, Jim; Paolini, Antonio G

2014-09-01

Early life events, such as calorie restriction (CR) and elevated glucocorticoids, can calibrate the lifelong behavioural and physiological profile of an individual. Stress reactivity in adulthood is particularly sensitive to early life events; however, the consequence to fear and anxiety-like behaviour is less clear. Consequently, the current study sought to examine the effects of post-natal CR and glucocorticoid elevation, long considered powerful programming stimuli, on the subsequent fear and anxiety behaviour of the adult offspring. Rat dams received either corticosterone (200 μg/ml) supplementation in drinking water (CORT) or a 25% CR from post-natal day (PND) 1 to 11. Responses to the elevated plus maze (EPM), open field and a predator odour (TMT; 2,5-dihydro-2,4,5-trimethylthiazoline) were characterised in the adult male offspring. Both treatment conditions resulted in enhanced fear responses to TMT, characterised by heightened risk assessment and increased avoidance of TMT. CORT nursed offspring further demonstrated an anxiogenic profile in the open field. Basal hypothalamic-pituitary-adrenal function was unchanged in CORT adult offspring, whilst corticosterone concentration was elevated by post-natal CR. CR and CORT treated dams both exhibited greater anxiety-like behaviour in the EPM. A modest and temporary enhancement of maternal care was observed in CR and CORT treated dams, with CR dams further exhibiting rapid pup retrieval latencies. The results indicate enhanced emotionality in the adult male progeny of dams exposed to CR and corticosterone supplementation during the post-natal period. The modest enhancement of maternal care observed by both treatments is unlikely to have influenced the behavioural profile of the offspring. Copyright © 2014. Published by Elsevier Inc.

Stress responding in cannabis smokers as a function of trauma exposure, sex, and relapse in the human laboratory.

PubMed

Chao, Thomas; Radoncic, Vanya; Hien, Denise; Bedi, Gillinder; Haney, Margaret

2018-04-01

Stress responding is linked to drug use, but little is known about stress responses in cannabis smokers. We investigated acute stress responding in cannabis smokers as a function of trauma exposure and sex, and relationships between stress responses and cannabis relapse. 125 healthy, non-treatment-seeking daily cannabis smokers (23F, 102 M) completed the Trier Social Stress Task (TSST), a standardized laboratory stressor; subsets also completed a trauma questionnaire (n = 106) and a laboratory cannabis relapse measure (n = 54). Stress responding was assessed with heart rate (HR), salivary cortisol (CORT), and self-rated mood. Cannabis smokers reporting at least one trauma exposure had higher CORT and anxiety overall compared to those reporting no trauma. Stress responding did not differ as a function of binary trauma exposure, although total number of exposures correlated positively with CORT and anxiety during stress. Females reported increased nervousness after stress relative to males matched to the females for cannabis and cigarette use. An interactive effect of sex and trauma on HR suggested that females with trauma exposure have increased cardiovascular stress responding relative to those without such exposure, with no differential effect in males. Stress responding did not predict laboratory cannabis relapse. We report differences in acute stress responding as a function of trauma, sex, and their interaction in a large sample of relatively homogenous cannabis smokers. Further investigation of how trauma impacts stress responding in male and female cannabis smokers, and how this relates to different aspects of cannabis use, is warranted. Copyright © 2018 Elsevier B.V. All rights reserved.

Repeated restraint stress-induced atrophy of glutamatergic pyramidal neurons and decreases in glutamatergic efflux in the rat amygdala are prevented by the antidepressant agomelatine.

PubMed

Grillo, C A; Risher, M; Macht, V A; Bumgardner, A L; Hang, A; Gabriel, C; Mocaër, E; Piroli, G G; Fadel, J R; Reagan, L P

2015-01-22

Major depressive illness is among the most prevalent neuropsychiatric disorders and is associated with neuroplasticity deficits in limbic structures such as the amygdala. Since exposure to stressful life events is proposed to contribute to depressive illness, our recent studies examined the effects of stress on amygdalar neuroplasticity. These studies determined that repeated stress elicits deficits in glutamatergic activity in the amygdala, neuroplasticity deficits that can be prevented by some but not all antidepressants. In view of these observations, the goal of the current study was to determine the effects of repeated restraint stress (RRS) on the dendritic architecture of pyramidal neurons in the rat basolateral nucleus of the amygdala (CBL), as well as glutamate efflux in the CBL and central nucleus of the amygdala (CMX) via in vivo microdialysis. We also examined the ability of the antidepressant agomelatine to prevent RRS-induced neuroplasticity deficits. Compared with control rats, rats subjected to RRS exhibited atrophy of CBL pyramidal neurons, including decreases in total dendritic length, branch points, and dendritic complexity index. In addition, glutamate efflux was significantly reduced in the CMX of rats subjected to RRS, thereby identifying a potential neurochemical consequence of stress-induced dendritic atrophy of CBL pyramidal neurons. Lastly, an acute stress challenge increased corticosterone (CORT) levels in the CBL, suggesting that stress-induced increases in CORT levels may contribute to the neuroanatomical and neurochemical effects of RRS in the CBL. Importantly, these RRS-induced changes were prevented by daily agomelatine administration. These results demonstrate that the neuroanatomical and neurochemical properties of glutamatergic neurons in the rat amygdala are adversely affected by repeated stress and suggest that the therapeutic effects of agomelatine may include protection of structural and neurochemical plasticity in limbic structures like the amygdala. Published by Elsevier Ltd.

Blue light filtered white light induces depression-like responses and temporary spatial learning deficits in rats.

PubMed

Meng, Qinghe; Lian, Yuzheng; Jiang, Jianjun; Wang, Wei; Hou, Xiaohong; Pan, Yao; Chu, Hongqian; Shang, Lanqin; Wei, Xuetao; Hao, Weidong

2018-04-18

Ambient light has a vital impact on mood and cognitive functions. Blue light has been previously reported to play a salient role in the antidepressant effect via melanopsin. Whether blue light filtered white light (BFW) affects mood and cognitive functions remains unclear. The present study aimed to investigate whether BFW led to depression-like symptoms and cognitive deficits including spatial learning and memory abilities in rats, and whether they were associated with the light-responsive function in retinal explants. Male Sprague-Dawley albino rats were randomly divided into 2 groups (n = 10) and treated with a white light-emitting diode (LED) light source and BFW light source, respectively, under a standard 12 : 12 h L/D condition over 30 days. The sucrose consumption test, forced swim test (FST) and the level of plasma corticosterone (CORT) were employed to evaluate depression-like symptoms in rats. Cognitive functions were assessed by the Morris water maze (MWM) test. A multi-electrode array (MEA) system was utilized to measure electro-retinogram (ERG) responses induced by white or BFW flashes. The effect of BFW over 30 days on depression-like responses in rats was indicated by decreased sucrose consumption in the sucrose consumption test, an increased immobility time in the FST and an elevated level of plasma CORT. BFW led to temporary spatial learning deficits in rats, which was evidenced by prolonged escape latency and swimming distances in the spatial navigation test. However, no changes were observed in the short memory ability of rats treated with BFW. The micro-ERG results showed a delayed implicit time and reduced amplitudes evoked by BFW flashes compared to the white flash group. BFW induces depression-like symptoms and temporary spatial learning deficits in rats, which might be closely related to the impairment of light-evoked output signals in the retina.

Role of Hemidivisional Corneal Topographic Astigmatisms (CorTs) in the Regularization and Reduction of Irregular Astigmatism.

PubMed

Alpins, Noel; Ong, James K Y; Stamatelatos, George

2018-03-01

To demonstrate how the concept of hemidivisional corneal topographic astigmatism (hemiCorT) enables the planning of hemidivisional corneal treatments to reduce irregularity and overall astigmatism. Whole-of-cornea corneal topographic astigmatism (CorT) is calculated from topography data derived from a corneal topographer or tomographer. The cornea is conceptually divided into 2 hemidivisions along the flat meridian of the CorT. For each hemidivision, hemiCorTs are calculated. The regularization treatment for each hemidivision is the treatment required to target the whole-of-cornea CorT, which is a symmetrical orthogonal corneal astigmatism. The regularization is then combined with astigmatism reduction treatment, which could be a conventional refractive treatment or a vector-planned treatment. For each hemidivision, the combined astigmatic effect of the regularization treatment and reduction treatment can be determined through double-angle vector summation. The 2 hemidivisional treatments together regularize and reduce corneal astigmatism. A theoretical pair of hemidivisional treatments is derived from an actual example of a cornea displaying idiopathic asymmetric nonorthogonal astigmatism. HemiCorTs allow for the design of hemidivisional corneal treatments of asymmetric nonorthogonal astigmatism. Such treatments should be suitable in the routine treatment of commonly occurring irregular astigmatism, while also allowing the spherical refractive error to be treated concurrently.

Adolescent Corticosterone and TrkB Pharmaco-Manipulations Sex-Dependently Impact Instrumental Reversal Learning Later in Life

PubMed Central

Barfield, Elizabeth T.; Gourley, Shannon L.

2017-01-01

Early-life trauma can increase the risk for, and severity of, several psychiatric illnesses. These include drug use disorders, and some correlations appear to be stronger in women. Understanding the long-term consequences of developmental stressor or stress hormone exposure and possible sex differences is critically important. So-called “reversal learning” tasks are commonly used in rodents to model cognitive deficits in stress- and addiction-related illnesses in humans. Here, we exposed mice to the primary stress hormone corticosterone (CORT) during early adolescence (postnatal days 31–42), then tested behavioral flexibility in adulthood using an instrumental reversal learning task. CORT-exposed female, but not male, mice developed perseverative errors. Despite resilience to subchronic CORT exposure, males developed reversal performance impairments following exposure to physical stressors. Administration of a putative tyrosine kinase receptor B (trkB) agonist, 7,8-dihydroxyflavone (7,8-DHF), during adolescence blocked CORT-induced errors in females and improved performance in males. Conversely, blockade of trkB by ANA-12 impaired performance. These data suggest that trkB-based interventions could have certain protective benefits in the context of early-life stressor exposure. We consider the implications of our findings in an extended “Discussion” section. PMID:29270114

Antidepressant-like effects of oleoylethanolamide in a mouse model of chronic unpredictable mild stress.

PubMed

Jin, Peng; Yu, Hai-Ling; Tian-Lan; Zhang, Feng; Quan, Zhe-Shan

2015-06-01

Oleoylethanolamide (OEA) is an endocannabinoid analog that belongs to a family of endogenous acylethanolamides. Increasing evidence suggests that OEA may act as an endogenous neuroprotective factor and participate in the control of mental disorder-related behaviors. In this study, we examined whether OEA is effective against depression and investigated the role of circulating endogenous acylethanolamides during stress. Mice were subjected to 28days of chronic unpredictable mild stress (CUMS), and during the last 21days, treated with oral OEA (1.5-6mg/kg) or 6mg/kg fluoxetine. Sucrose preference and open field test activity were used to evaluate depression-like behaviors during CUMS and after OEA treatment. Weights of the prefrontal cortex and hippocampus were determined, and the adrenal index was measured. Furthermore, changes in serum adrenocorticotropic hormone (ACTH), corticosterone (CORT) and total antioxidant capacity (T-AOC), brain-derived neurotrophic factor (BDNF), and lipid peroxidation product malondialdehyde (MDA) levels, and superoxide dismutase (SOD) activities in the hippocampus and prefrontal cortex were detected. Our findings indicate that OEA normalized sucrose preferences, locomotion distances, rearing frequencies, prefrontal cortex and hippocampal atrophy, and adrenal indices. In addition, OEA reversed the abnormalities of BDNF and MDA levels and SOD activities in the hippocampus and prefrontal cortex, as well as changes in serum levels of ACTH, CORT, and T-AOC. The antidepressant effects of OEA may be related to the regulation of BDNF levels in the hippocampus and prefrontal cortex, antioxidant defenses, and normalizing hyperactivity in the hypothalamic-pituitary-adrenal axis (HPA). Copyright © 2015 Elsevier Inc. All rights reserved.

Stress and Traumatic Brain Injury: A Behavioral, Proteomics, and Histological Study

DTIC Science & Technology

2011-03-07

time point. They had elevated levels of serum corticosterone (CORT) and hippocampal IL-6 but no other cellular or protein changes. Stressed injured...rats had an increased number of TUNEL-positive cells in the HC and elevated GFAP and Iba1 immunoreactivity in the HC and the PFC. Our findings suggest...neuronal and glial cell loss, inflammation, and gliosis. These findings may have implications in the development of diagnostic and therapeutic measures

Early maternal separation followed by later stressors leads to dysregulation of the HPA-axis and increases in hippocampal NGF and NT-3 levels in a rat model.

PubMed

Faure, Jacqueline; Uys, Joachim D K; Marais, Lelanie; Stein, Dan J; Daniels, Willie M U

2006-09-01

Early adverse life events, followed by subsequent stressors, appear to increase susceptibility for subsequent onset of psychiatric disorders in humans. The molecular mechanisms that underlie this phenomenon remain unclear, but dysregulation of the HPA axis and alterations in neurotrophic factors have been implicated. The present study investigated the effects in rodents of early maternal separation, followed by stress in adolescence and adulthood on later HPA-axis activity and hippocampal neurotrophin levels (brain-derived neurotrophic factor, nerve growth factor, and neurotrophin-3). Animals subjected to repeated stressors showed a significant decrease in basal ACTH (p < 0.05) and CORT (p < 0.05) levels when compared to controls, as well as significantly increased levels of NGF in the dorsal (p < 0.001) and ventral hippocampus (p < 0.01), and of NT-3 in the dorsal hippocampus (p < 0.01). Dysregulation of the HPA axis after multiple stressors is consistent with previous preclinical and clinical work. Given that neurotrophins are important in neuronal survival and plasticity, it is possible to speculate that their elevation reflects a compensatory mechanism.

Genetic Architecture of Palm Oil Fatty Acid Composition in Cultivated Oil Palm (Elaeis guineensis Jacq.) Compared to Its Wild Relative E. oleifera (H.B.K) Cortés

PubMed Central

Montoya, Carmenza; Cochard, Benoit; Flori, Albert; Cros, David; Lopes, Ricardo; Cuellar, Teresa; Espeout, Sandra; Syaputra, Indra; Villeneuve, Pierre; Pina, Michel; Ritter, Enrique; Leroy, Thierry; Billotte, Norbert

2014-01-01

We searched for quantitative trait loci (QTL) associated with the palm oil fatty acid composition of mature fruits of the oil palm E. guineensis Jacq. in comparison with its wild relative E. oleifera (H.B.K) Cortés. The oil palm cross LM2T x DA10D between two heterozygous parents was considered in our experiment as an intraspecific representative of E. guineensis. Its QTLs were compared to QTLs published for the same traits in an interspecific Elaeis pseudo-backcross used as an indirect representative of E. oleifera. Few correlations were found in E. guineensis between pulp fatty acid proportions and yield traits, allowing for the rather independent selection of both types of traits. Sixteen QTLs affecting palm oil fatty acid proportions and iodine value were identified in oil palm. The phenotypic variation explained by the detected QTLs was low to medium in E. guineensis, ranging between 10% and 36%. The explained cumulative variation was 29% for palmitic acid C16:0 (one QTL), 68% for stearic acid C18:0 (two QTLs), 50% for oleic acid C18:1 (three QTLs), 25% for linoleic acid C18:2 (one QTL), and 40% (two QTLs) for the iodine value. Good marker co-linearity was observed between the intraspecific and interspecific Simple Sequence Repeat (SSR) linkage maps. Specific QTL regions for several traits were found in each mapping population. Our comparative QTL results in both E. guineensis and interspecific materials strongly suggest that, apart from two common QTL zones, there are two specific QTL regions with major effects, which might be one in E. guineensis, the other in E. oleifera, which are independent of each other and harbor QTLs for several traits, indicating either pleiotropic effects or linkage. Using QTL maps connected by highly transferable SSR markers, our study established a good basis to decipher in the future such hypothesis at the Elaeis genus level. PMID:24816555

Genetic architecture of palm oil fatty acid composition in cultivated oil palm (Elaeis guineensis Jacq.) compared to its wild relative E. oleifera (H.B.K) Cortés.

PubMed

Montoya, Carmenza; Cochard, Benoit; Flori, Albert; Cros, David; Lopes, Ricardo; Cuellar, Teresa; Espeout, Sandra; Syaputra, Indra; Villeneuve, Pierre; Pina, Michel; Ritter, Enrique; Leroy, Thierry; Billotte, Norbert

2014-01-01

We searched for quantitative trait loci (QTL) associated with the palm oil fatty acid composition of mature fruits of the oil palm E. guineensis Jacq. in comparison with its wild relative E. oleifera (H.B.K) Cortés. The oil palm cross LM2T x DA10D between two heterozygous parents was considered in our experiment as an intraspecific representative of E. guineensis. Its QTLs were compared to QTLs published for the same traits in an interspecific Elaeis pseudo-backcross used as an indirect representative of E. oleifera. Few correlations were found in E. guineensis between pulp fatty acid proportions and yield traits, allowing for the rather independent selection of both types of traits. Sixteen QTLs affecting palm oil fatty acid proportions and iodine value were identified in oil palm. The phenotypic variation explained by the detected QTLs was low to medium in E. guineensis, ranging between 10% and 36%. The explained cumulative variation was 29% for palmitic acid C16:0 (one QTL), 68% for stearic acid C18:0 (two QTLs), 50% for oleic acid C18:1 (three QTLs), 25% for linoleic acid C18:2 (one QTL), and 40% (two QTLs) for the iodine value. Good marker co-linearity was observed between the intraspecific and interspecific Simple Sequence Repeat (SSR) linkage maps. Specific QTL regions for several traits were found in each mapping population. Our comparative QTL results in both E. guineensis and interspecific materials strongly suggest that, apart from two common QTL zones, there are two specific QTL regions with major effects, which might be one in E. guineensis, the other in E. oleifera, which are independent of each other and harbor QTLs for several traits, indicating either pleiotropic effects or linkage. Using QTL maps connected by highly transferable SSR markers, our study established a good basis to decipher in the future such hypothesis at the Elaeis genus level.

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2014-06-01

astrocyte activation can be seen in the CA1 region of the hippocampus (Figure 4). Neither IBA1 nor GFAP showed obvious increases in any other brain...0 4 8 IL6 DFP CORT DFP * * * 14 Chronic CORT pretreatment exacerbated the DFP-induced increase in activation of astrocytes specific to the CA1...may have caused a mild activation of astrocytes (Figure 18), there was no quantitative change in GFAP protein concentration in the hippocampus (data

Stress Responses to Heat Exposure in Three Species of Australian Desert Birds.

PubMed

Xie, Shangzhe; Romero, L Michael; Htut, Zaw Win; McWhorter, Todd J

Birds need to respond to weather changes quickly and appropriately for their own well-being and survival. The inability to respond appropriately to heat waves can be fatal to individual birds and can translate into large-scale mortality events. We investigated corticosterone (CORT) and heterophil∶lymphocyte (H∶L) ratio responses of budgerigars (Melopsittacus undulatus), zebra finches (Taeniopygia guttata), and diamond doves (Geopelia cuneata) to heat exposures. The birds were exposed to a temperature similar to what they experience during a typical summer day (35°C) and a higher temperature (45°C) similar to that experienced during a heat wave. There were no significant increases between the CORT concentrations before and after heat exposure in zebra finches and budgerigars at 35° and 45°C, but there was a significant increase in CORT concentrations in diamond doves after exposure to 45°C. The H∶L ratios increased significantly after heat exposure in budgerigars at 35° and 45°C and in diamond doves at 35°C. No significant correlation was found between the changes in CORT and H∶L ratios. The data suggest that there are species differences in birds' stress responses to heat exposure that may reflect their ability to detect and adapt to high temperatures. There appear to be differences between the two types of stress measurements, which may reflect differences in the timescales of these responses.

Coupling corticotropin-releasing-hormone and angiotensin converting enzyme 2 dampens stress responsiveness in male mice.

PubMed

Wang, Lei A; de Kloet, Annette D; Smeltzer, Michael D; Cahill, Karlena M; Hiller, Helmut; Bruce, Erin B; Pioquinto, David J; Ludin, Jacob A; Katovich, Michael J; Raizada, Mohan K; Krause, Eric G

2018-05-01

This study used mice to evaluate whether coupling expression of corticotropin-releasing hormone (CRH) and angiotensin converting enzyme 2 (ACE2) creates central interactions that blunt endocrine and behavioral responses to psychogenic stress. Central administration of diminazene aceturate, an ACE2 activator, had no effect on restraint-induced activation of the hypothalamic-pituitary-adrenal (HPA) axis; however, mice that ubiquitously overexpress ACE2 had reduced plasma corticosterone (CORT) and pituitary expression of POMC mRNA. The Cre-LoxP system was used to restrict ACE2 overexpression to CRH synthesizing cells and probe whether HPA axis suppression was the result of central ACE2 and CRH interactions. Within the paraventricular nucleus of the hypothalamus (PVN), mice with ACE2 overexpression directed to CRH had a ≈2.5 fold increase in ACE2 mRNA, which co-localized with CRH mRNA. Relative to controls, mice overexpressing ACE2 in CRH cells had a decreased CORT response to restraint as well as decreased CRH mRNA in the PVN and CEA and POMC mRNA in the pituitary. Administration of ACTH similarly increased plasma CORT, indicating that the blunted HPA axis activation that accompanies ACE2 overexpression in CRH cells is centrally mediated. Anxiety-like behavior was assessed to determine whether the decreased HPA axis activation was predictive of anxiolysis. Mice with ACE2 overexpression directed to CRH cells displayed decreased anxiety-like behavior in the elevated plus maze and open field when compared to that of controls. Collectively, these results suggest that exogenous ACE2 suppresses CRH synthesis, which alters the central processing of psychogenic stress, thereby blunting HPA axis activation and attenuating anxiety-like behavior. Copyright © 2018 Elsevier Ltd. All rights reserved.

Angiotensin type 1 receptors in the subfornical organ mediate the drinking and hypothalamic-pituitary-adrenal response to systemic isoproterenol.

PubMed

Krause, Eric G; Melhorn, Susan J; Davis, Jon F; Scott, Karen A; Ma, Li Y; de Kloet, Annette D; Benoit, Stephen C; Woods, Stephen C; Sakai, Randall R

2008-12-01

Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a beta-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT1R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII.

Angiotensin Type 1 Receptors in the Subfornical Organ Mediate the Drinking and Hypothalamic-Pituitary-Adrenal Response to Systemic Isoproterenol

PubMed Central

Krause, Eric G.; Melhorn, Susan J.; Davis, Jon F.; Scott, Karen A.; Ma, Li Y.; de Kloet, Annette D.; Benoit, Stephen C.; Woods, Stephen C.; Sakai, Randall R.

2008-01-01

Circulating angiotensin II (ANGII) elicits water intake and activates the hypothalamic-pituitary-adrenal (HPA) axis by stimulating angiotensin type 1 receptors (AT1Rs) within circumventricular organs. The subfornical organ (SFO) and the organum vasculosum of the lamina terminalis (OVLT) are circumventricular organs that express AT1Rs that bind blood-borne ANGII and stimulate integrative and effector regions of the brain. The goal of these studies was to determine the contribution of AT1Rs within the SFO and OVLT to the water intake and HPA response to increased circulating ANGII. Antisense oligonucleotides directed against the AT1R [AT1R antisense (AT1R AS)] were administered into the OVLT or SFO. Quantitative receptor autoradiography confirmed that AT1R AS decreased ANGII binding in the SFO and OVLT compared with the scrambled sequence control but did not affect AT1R binding in other nuclei. Subsequently, water intake, ACTH, and corticosterone (CORT) were assessed after administration of isoproterenol, a β-adrenergic agonist that decreases blood pressure and elevates circulating ANGII. Delivery of AT1R AS into the SFO attenuated water intake, ACTH, and CORT after isoproterenol, whereas similar treatment in the OVLT had no effect. To determine the specificity of this blunted drinking and HPA response, the same parameters were measured after treatment with hypertonic saline, a stimulus that induces drinking independently of ANGII. Delivery of AT1R AS into the SFO or OVLT had no effect on water intake, ACTH, or CORT after hypertonic saline. The results imply that AT1R within the SFO mediate drinking and HPA responses to stimuli that increase circulating ANGII. PMID:18687780

Are Invasive Species Stressful? The Glucocorticoid Profile of Native Lizards Exposed to Invasive Fire Ants Depends on the Context.

PubMed

Graham, Sean P; Freidenfelds, Nicole A; Thawley, Christopher J; Robbins, Travis R; Langkilde, Tracy

Invasive species represent a substantial threat to native species worldwide. Research on the impacts of invasive species on wild living vertebrates has focused primarily on population-level effects. The sublethal, individual-level effects of invaders may be equally important but are poorly understood. We investigated the effects of invasive fire ants (Solenopsis invicta) on the physiological stress response of a native lizard (Sceloporus undulatus) within two experimental contexts: directly exposing lizards to a fire ant attack and housing lizards with fire ants in seminatural field enclosures. Lizards directly exposed to brief attack by fire ants had elevated concentrations of the stress hormone corticosterone (CORT), suggesting that these encounters can be physiologically stressful. However, lizards exposed for longer periods to fire ants in field enclosures had lower concentrations of CORT. This may indicate that the combined effects of confinement and fire ant exposure have pushed lizards into allostatic overload. However, lizards from fire ant enclosures appeared to have intact negative feedback controls of the stress response, evidenced by functioning adrenocorticotropic hormone responsiveness and lack of suppression of innate immunity (plasma bactericidal capacity). We review previous studies examining the stress response of wild vertebrates to various anthropogenic stressors and discuss how these-in combination with our results-underscore the importance of considering context (the length, frequency, magnitude, and types of threat) when assessing these impacts.

Body Mass Changes Associated With Hyper-Gravity are Independent of Adrenal Derived Hormones

NASA Technical Reports Server (NTRS)

Wade, Charles E.; Moran, Megan M.; Wang, Tommy J.; Baer, Lisa A.; Yuan, Fang; Fung, Cyra K.; Stein, T. Peter; Dalton, Bonnie P. (Technical Monitor)

2001-01-01

Exposure to hyper-gravity results in a number of metabolic changes associated with increases in catecholamines and corticosterone. These changes result in a loss of body and fat mass. To assess the role of hormones derived from the adrenal gland in the changes we studied sham operated (SO) and adrenalectomized (ADX) male rats exposed to hyper-gravity of 2 G for 14 days. Control groups at 1 G were also studied. Urinary epinephrine (EPI) and corticosterone (CORT) were reduced in ADX animals. In response to 2 G there was an increase in urinary EPI and CORT in SO rats, while levels were unchanged in ADX animals. Both groups of animals had similar increases in urinary norepinephrine levels. The reductions of body mass gain in response to 2 G were the same in both groups. The decrease in relative fat mass was greater in ADX. Energy intake and expenditure were not different between groups. In response of returning to 1 G for 24 hours and reexposure to hyper-gravity there were no differences between SO and ADX in the changes of food and water intake, body mass or activity. The changes in metabolism with exposure to hyper-gravity do not appear to require hormones derived from the adrenal gland. The increase in lypolysis and alterations body and fat mass appear to be modulated by sympathetically derived norepinehrine.

Piper sarmentosum Roxb. produces antidepressant-like effects in rodents, associated with activation of the CREB-BDNF-ERK signaling pathway and reversal of HPA axis hyperactivity.

PubMed

Li, Qing; Qu, Fa-Lin; Gao, Yue; Jiang, Yi-Ping; Rahman, Khalid; Lee, Kuo-Hsiung; Han, Ting; Qin, Lu-Ping

2017-03-06

There are many plants of genus Piper which have been reported to induce antidepressant-like effects, Piper sarmentosum (PS) is one of them. PS is a Chinese herbal medicine and a traditional edible vegetable. In the present study, the antidepressant-like effects of PS extracts and the ethyl acetate fraction of PS extracts (PSY) were assessed using the open field test (OFT), forced swimming test (FST), and tail suspension test (TST) in mice. Furthermore, we applied a 4 consecutive weeks of chronic unpredictable mild stress (CUMS) as a model of depression in rats, followed by a sucrose preference test. Then we examined the possible mechanisms of this action. The activity of the hypothalamic-pituitary-adrenal (HPA) axis was evaluated by detecting the serum corticosterone (CORT) concentrations, and the protein expression levels of brain-derived neurotrophic factor (BDNF), the phosphorylated form CREB and ERK1/2 were detected by qRT-PCR or Western blot. The results showed that PS extracts (100, 200mg/kg) and PSY (12.5, 25, 50mg/kg) treatment produced antidepressant-like effects in mice similar to fluoxetine (20mg/kg), indicated by the reduced immobility time in the FST and TST, while both had no influence on the locomotor activity in the OFT. PSY treatment significantly increased sucrose preference and reduced serum CORT levels in CUMS rats. Moreover, PSY up-regulated BDNF protein levels, and increased CREB and ERK phosphorylation levels in the hippocampus on CUMS rats. These findings suggest that the antidepressant-like effects of PS extracts and PSY are mediated, at least in part, by modulating HPA axis, BDNF, CREB and ERK phosphorylation and expression in the hippocampus. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Articulating the strategies for maximising the inclusion of people with dementia in qualitative research studies.

PubMed

Murphy, Kathy; Jordan, Fionnuala; Hunter, Andrew; Cooney, Adeline; Casey, Dympna

2015-11-01

It is essential to understand the experience of living with dementia from the perspective of the person with dementia so that services can be appropriately constructed. This review paper, drawing on prior work, identifies key strategies for the meaningful inclusion of persons with dementia within qualitative research studies, it examines the articulation of these strategies and shares how these strategies were operationalised within one national research study in Ireland. Strategies within the literature were categorised and then synthesized into a guide consisting of four main areas; gaining COnsent, maximizing Responses, Telling the story, and Ending on a high (CORTE). The CORTE guideline was used to as a tool for analysing relevant research reports. CORTE is a synthesized account of grouped strategies that could be used to maximize the meaningful involvement of persons with dementia and can also provide a guide for reporting the strategies used so that researchers can learn from each other. © The Author(s) 2014.

Glucocorticoid interactions with ethanol effects on depolarization-induced calcium influx in brain synaptosomes.

PubMed

Sze, P Y

1996-04-01

Depolarization-induced Ca2+ influx in brain synaptosomes is known to be inhibited by ethanol and stimulated by glucocorticoids. The present study was undertaken to characterize the interactions of corticosterone (CORT) with ethanol effects on 45Ca2+ uptake in synaptosomes depolarized by high K+ (70 mM). CORT was shown to antagonize the inhibitory effects of ethanol on the fast-phase component of the K(+)-induced 45Ca2+ uptake (the initial 3 s following depolarization). Glucocorticoid antagonism of ethanol inhibition of the 45Ca2+ uptake exhibited a high degree of steroid specificity; steroids with glucocorticoid activity including cortisol, dexamethasone and triamcinolone were effective, whereas gonadal steroids and excitatory neuroactive steroid metabolites were ineffective. From the shift of concentration-response relationships when CORT and ethanol were present in combination, the interaction between steroid stimulation and ethanol inhibition of 45Ca2+ uptake occurred in an additive manner over the range of their effective concentrations. Parallel to 45Ca2+ uptake, the binding sites for [3H]PN 200-110 were reduced by ethanol and increased by CORT. These opposite effects on [3H]dihydropyridine labeled sites were found also to antagonize each other, and the antagonism again occurred in an additive relationship. These results demonstrate that glucocorticoids antagonized ethanol inhibition of voltage-dependent Ca2+ channel activity in brain synaptosomes, and support the notion that these steroids may be among the endogenous factors that modulate neuronal sensitivity to ethanol.

Ratchet motion induced by a correlated stochastic force

NASA Astrophysics Data System (ADS)

Cortés, Emilio

2000-01-01

We apply a rigorous formalism we have just worked out (Cortés and Espinosa, Physica A 267 (1999) 414) about escape rates and the Hamilton-Jacobi equation, to study the ratchet motion of a Brownian particle and calculate the probability current in a periodic non-symmetric potential subject to correlated fluctuations. We are able to obtain the current behaviour as a function of the correlation time parameter and compare with other results in the literature.

[Sense of guilt in sexually abused children : Mediating role of avoidance coping on anxiety and self-esteem].

PubMed

Gauthier-Duchesne, Amélie; Hébert, Martine; Daspe, Marie-Ève

2017-01-01

Prior studies have suggested self-blame and sense of guilt as important elements associated with the effects of childhood sexual abuse on adult survivors (Cantón-Cortés, Cantón, Justicia & Cortés, 2011). However, few studies have explored the potential impact of the sense of guilt on outcomes in child victims. This study examines the mediating role of avoidance coping on the relationship between sense of guilt and outcomes (anxiety and self-esteem) in sexually abused children. The sample consisted of 447 sexually abused children (319 girls and 128 boys) aged 6 to 12. Path analysis indicated that children with higher feelings of guilt about the abuse showed more anxiety and lower levels of self-esteem. Indirect effects also indicated that sense of guilt predicted avoidance coping, which in turn contributed to higher anxiety and lower self-esteem. This model, which fits the data well for both girls and boys, explains 24.4 % of the variance in anxiety and 11.2 % of the variance in self-esteem. Results suggest that sense of guilt is an important target for clinical intervention with sexually abused children.

Tear Film Steroid Profiling in Dry Eye Disease by Liquid Chromatography Tandem Mass Spectrometry

PubMed Central

Agnifili, Luca; Cicalini, Ilaria; Calienno, Roberta; Zucchelli, Mirco; Mastropasqua, Leonardo; Sacchetta, Paolo; Del Boccio, Piero; Rossi, Claudia

2017-01-01

Dry eye disease (DED) is a multifactorial disorder of the ocular surface unit resulting in eye discomfort, visual disturbance, and ocular surface damage; the risk of DED increases with age in both sexes, while its incidence is higher among females caused by an overall hormonal imbalance. The role of androgens has recently investigated and these hormones were considered to have a protective function on the ocular surface. In order to correlate DED to tear steroid levels, a robust, specific, and selective method for the simultaneous quantification of cortisol (CORT), corticosterone (CCONE), 11-deoxycortisol (11-DECOL), 4-androstene-3,17-dione (ADIONE), testosterone (TESTO), 17α-hydroxyprogesterone (17-OHP), and progesterone (PROG) was developed and applied for the analysis of tear samples. The method involves a simple extraction procedure of steroids from tears collected on Schirmer strips, followed by a high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In total, tear samples from 14 DED female patients and 13 healthy female controls were analysed and, CORT, ADIONE, and 17-OHP response levels resulted significantly decreased in dry eye patients respect to controls. The receiver operating characteristic (ROC) curve obtained by the combination of these three steroids (AUC = 0.964) demonstrated the good diagnostic power of the differential tear steroids in identifying DED. In conclusion, the present method made it possible, for the first time, to study steroid profiling directly in tear fluid. PMID:28672794

Development of Analytical Systems for Evaluation of US Reconstitution and Recovery Programs.

DTIC Science & Technology

1980-09-01

Program Evaluation Economic M4odels US Economy ’MABB"ACT (Cort~at m~ Mae @0b neamv md kavily by block numbr) ~This study identifies economic models and...planning tasks Are more complex and difficult than those faced by planners In the post 󈧬s era. Also, because of those same factors and that the 1980s...comparative analysis outlined in the second study , while also concerned with the accomplishment of societal objectives, is somewhat different. The approach

Msx-2 expression and glucocorticoid-induced overexpression in embryonic mouse submandibular glands.

PubMed

Jaskoll, T; Luo, W; Snead, M L

1998-01-01

It is well known that the process of branching morphogenesis requires epithelial-mesenchymal interactions. One outstanding model for the study of tissue interactions during branching morphogenesis is the embryonic mouse submandibular gland (SMG). Although it has been clearly demonstrated that the branching pattern is dependent on interactions between the epithelium and the surrounding mesenchyme, little is known about the molecular mechanism underlying the branching process. One group of transcription factors that likely participates in the control of epithelial-mesenchymal inductive interactions are the Msx-class of homeodomain-containing proteins. In this paper, we focus on Msx-2 because its developmental expression is correlated with inductive interactions, suggesting that Msx-2 may play a functional role during cell-cell interactions. We demonstrate the expression of Msx-2 mRNA and protein to be primarily in the branching epithelia with progressive embryonic (E13 to E15) SMG development and, to a lesser extent, in the mesenchyme. We also show that Msx-2 is expressed by embryonic SMG primordia cultured under defined conditions. In addition, to begin to delineate a functional role for Msx-2, we employed an experimental strategy by using exogenous glucocorticoid (CORT) treatment of embryonic SMGs in vitro and in vivo to significantly enhance branching morphogenesis and evaluate the effect of CORT treatment on embryonic SMG Msx-2 expression. A marked increase in Msx-2 transcripts and protein is detected with in vitro and in vivo CORT treatment. Our studies indicate that one mechanism of CORT regulation of salivary gland morphogenesis is likely through the modulation of Msx-2 gene expression.

Tissue-Specific Expression of DNA Methyltransferases Involved in Early-Life Nutritional Stress of Chicken, Gallus gallus

PubMed Central

Kang, Seong W.; Madkour, Mahmoud; Kuenzel, Wayne J.

2017-01-01

DNA methylation was reported as a possible stress-adaptation mechanism involved in the transcriptional regulation of stress responsive genes. Limited data are available on effects of psychological stress and early-life nutritional stress on DNA methylation regulators [DNMTs: DNA (cytosine-5)-methyltransferase 1 (DNMT1), DNMT1 associated protein (DMAP1), DNMT 3 alpha (DNMT3A) and beta (DNMT3B)] in avian species. The objectives of this study were to: (1) investigate changes in expression of DNMT1, DMAP1, DNMT3A, and DNMT3B following acute (AS) or chronic immobilization stress (CS); (2) test immediate effect of early-life nutritional stress [food deprivation (FD) for 12 h (12hFD) or 36 h (36hFD) at the post-hatching period] on expression of DNA methylation regulators and glucocorticoid receptor (GR), and the long-term effect of early-life nutritional stress at 6 weeks of age. Expression of DNMTs and plasma corticosterone (CORT) concentration decreased by CS compared to AS (p < 0.05), indicating differential roles of DNA methylation regulators in the stress response. Plasma CORT at 12hFD and 36hFD birds increased compared to control birds (12hF and 36hF), but there were no significant differences in plasma CORT of 12hFD and 36hFD birds at 6 weeks of age compared to 6 week controls. DNMT1, DMAP1, and DNMT3B expression in the anterior pituitary increased by 12hFD, but decreased at 36hFD compared to their controls (P < 0.05). In liver, DNMT1, DNMT3A, and DNMT3B expression decreased by 12hFD, however, no significant changes occurred at 36hFD. Expression of DMAP1, DNMT3A, and DNMT3B in anterior pituitary and DMAP1 and DNMT3A expression in liver at 6 weeks of age were higher in 36hFD stressed birds compared to controls as well as 12hFD stressed birds. Hepatic GR expression decreased by 12hFD and increased by 36hFD (p < 0.05). Expression patterns of GR in the liver of FD stress-induced birds persisted until 6 weeks of age, suggesting the possible lifelong involvement of liver GR in early-life nutritional stress response of birds. Taken together, results suggest that DNA methylation regulator genes are tissue-specifically responsive to acute and chronic stress, and hepatic GR may play a critical role in regulating the early-life nutritional stress response of birds. In addition, the downregulation of DNMT1 and DMAP1 may be one of the adaptive mechanisms to chronic early-life nutritional stress via passive demethylation. PMID:29270191

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex specific manner

PubMed Central

Dickens, M.J.; Balthazart, J.; Cornil, C. A.

2012-01-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, non-genomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce respectively a rapid inhibition or increase in preoptic aromatase activity (AA). Here, we tested quail that were either non-stressed or acutely stressed (15 min restraint) immediately prior to sexual interaction (5 min) with stressed or non-stressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (<5min) highlights the dynamic potential of the aromatase system to integrate input from stimuli that drive AA in opposing directions. Moreover, acute stress had minimal effects on male behaviour suggesting that the input from the sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: while males did not show any effect of partner status, females responded to both their stress exposure and the male partner’s stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner’s exhibition of sexually aggressive behaviour suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple – sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. In contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner’s stress exposure, and female-directed male behaviour. PMID:22612582

Prenatal ethanol exposure-induced adrenal developmental abnormality of male offspring rats and its possible intrauterine programming mechanisms

DOE Office of Scientific and Technical Information (OSTI.GOV)

Huang, Hegui; He, Zheng; Zhu, Chunyan

Fetal adrenal developmental status is the major determinant of fetal tissue maturation and offspring growth. We have previously proposed that prenatal ethanol exposure (PEE) suppresses fetal adrenal corticosterone (CORT) synthesis. Here, we focused on PEE-induced adrenal developmental abnormalities of male offspring rats before and after birth, and aimed to explore its intrauterine programming mechanisms. A rat model of intrauterine growth retardation (IUGR) was established by PEE (4 g/kg·d). In PEE fetus, increased serum CORT concentration and decreased insulin-like growth factor 1 (IGF1) concentration, with lower bodyweight and structural abnormalities as well as a decreased Ki67 expression (proliferative marker), were observedmore » in the male fetal adrenal cortex. Adrenal glucocorticoid (GC)-metabolic activation system was enhanced while gene expression of IGF1 signaling pathway with steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) was decreased. Furthermore, in the male adult offspring of PEE, serum CORT level was decreased but IGF1 was increased with partial catch-up growth, and Ki67 expression demonstrated no obvious change. Adrenal GC-metabolic activation system was inhibited, while IGF1 signaling pathway and 3β-HSD was enhanced with the steroidogenic factor 1 (SF1), and StAR was down-regulated in the adult adrenal. Based on these findings, we propose a “two-programming” mechanism for PEE-induced adrenal developmental toxicity: “the first programming” is a lower functional programming of adrenal steroidogenesis, and “the second programming” is GC-metabolic activation system-related GC-IGF1 axis programming. - Highlights: • Prenatal ethanol exposure induces adrenal developmental abnormality in offspring rats. • Prenatal ethanol exposure induces intrauterine programming of adrenal steroidogenesis. • Intrauterine GC-IGF1 axis programming might mediate adrenal developmental abnormality.« less

Brain aromatase and circulating corticosterone are rapidly regulated by combined acute stress and sexual interaction in a sex-specific manner.

PubMed

Dickens, M J; Balthazart, J; Cornil, C A

2012-10-01

Neural production of 17β-oestradiol via aromatisation of testosterone may play a critical role in rapid, nongenomic regulation of physiological and behavioural processes. In brain nuclei implicated in the control of sexual behaviour, sexual or stressfull stimuli induce, respectively, a rapid inhibition or increase in preoptic aromatase activity (AA). In the present study, we tested quail that were either nonstressed or acutely stressed (15 min of restraint) immediately before sexual interaction (5 min) with stressed or nonstressed partners. We measured nuclei-specific AA changes, corresponding behavioural output, fertilisation rates and corticosterone (CORT) concentrations. In males, sexual interaction rapidly reversed stress-induced increases of AA in the medial preoptic nucleus (POM). This time scale (< 5 min) highlights the dynamic potential of the aromatase system to integrate input from stimuli that drive AA in opposing directions. Moreover, acute stress had minimal effects on male behaviour, suggesting that the input from the sexual stimuli on POM AA may actively preserve sexual behaviour despite stress exposure. We also found distinct sex differences in contextual physiological responses: males did not show any effect of partner status, whereas females responded to both their stress exposure and the male partner's stress exposure at the level of circulating CORT and AA. In addition, fertilisation rates and female CORT correlated with the male partner's exhibition of sexually aggressive behaviour, suggesting that female perception of the male can affect their physiology as much as direct stress. Overall, male reproduction appears relatively simple: sexual stimuli, irrespective of stress, drives major neural changes including rapid reversal of stress-induced changes of AA. By contrast, female reproduction appears more nuanced and context specific, with subjects responding physiologically and behaviourally to stress, the male partner's stress exposure, and female-directed male behaviour. © 2012 The Authors. Journal of Neuroendocrinology © 2012 British Society for Neuroendocrinology.

The relationship between adjunctive drinking, blood ethanol concentration and plasma corticosterone across fixed-time intervals of food delivery in two inbred mouse strains.

PubMed

Ford, Matthew M; Steele, Andrea M; McCracken, Aubrey D; Finn, Deborah A; Grant, Kathleen A

2013-11-01

Schedules of intermittent food delivery induce excessive fluid intake, termed schedule-induced polydipsia (SIP), and hypothalamic-pituitary-adrenal (HPA) axis activation is important for the expression and maintenance of this adjunctive behavior. Previous work has focused on examining the relationship between water intake and plasma corticosterone (CORT) in rats at a single or a limited range of fixed time (FT) intervals. However, little remains known regarding SIP and the corresponding stress response (1) across the bitonic function that epitomizes adjunctive behavior, (2) when ethanol is the available fluid, and (3) when a species other than rat or multiple strains are studied. Here we report the findings from ethanol-preferring C57BL/6J (B6) and non-preferring DBA/2J (D2) mice serially exposed to progressively larger FT intervals (0 → 60 min) and given access to either water or a 5% (v/v) ethanol solution. Following 2 weeks of experience with each schedule, blood samples were collected at the conclusion of the last 60-min session to evaluate CORT and the blood ethanol concentration (BEC) achieved. While both strains exhibited a bitonic function of ethanol intake and BEC that peaked at or near a 5-min interval, only D2 mice showed a similar response with water. In contrast, CORT levels rose monotonically with incremental increases in the FT interval regardless of the strain examined or fluid type offered, indicating that glucocorticoid release likely reflects the aversive aspects of increasing intervals between reinforcement rather than engagement in adjunctive behavior. These findings also caution against the use of a single intensity stressor to evaluate the relationship between stress and ethanol intake, as the magnitude of stress appears to affect ethanol consumption in a non-linear fashion. Copyright © 2013 Elsevier Ltd. All rights reserved.

Effects of genes, sex, age, and activity on BMC, bone size, and areal and volumetric BMD.

PubMed

Havill, Lorena M; Mahaney, Michael C; L Binkley, Teresa; Specker, Bonny L

2007-05-01

Quantitative genetic analyses of bone data for 710 inter-related individuals 8-85 yr of age found high heritability estimates for BMC, bone area, and areal and volumetric BMD that varied across bone sites. Activity levels, especially time in moderate plus vigorous activity, had notable effects on bone. In some cases, these effects were age and sex specific. Genetic and environmental factors play a complex role in determining BMC, bone size, and BMD. This study assessed the heritability of bone measures; characterized the effects of age, sex, and physical activity on bone; and tested for age- and sex-specific bone effects of activity. Measures of bone size and areal and volumetric density (aBMD and vBMD, respectively) were obtained by DXA and pQCT on 710 related individuals (466 women) 8-85 yr of age. Measures of activity included percent time in moderate + vigorous activity (%ModVig), stair flights climbed per day, and miles walked per day. Quantitative genetic analyses were conducted to model the effects of activity and covariates on bone outcomes. Accounting for effects of age, sex, and activity levels, genes explained 40-62% of the residual variation in BMC and BMD and 27-75% in bone size (all p<0.001). Decline in femoral neck (FN), hip, and spine aBMD with advancing age was greater among women than men (age-by-sex interaction; all p

Hypothalamic-pituitary-adrenal axis and behavioral dysfunction following early binge-like prenatal alcohol exposure in mice.

PubMed

Wieczorek, Lindsay; Fish, Eric W; O'Leary-Moore, Shonagh K; Parnell, Scott E; Sulik, Kathleen K

2015-05-01

The range of defects that fall within fetal alcohol spectrum disorder (FASD) includes persistent behavioral problems, with anxiety and depression being two of the more commonly reported issues. Previous studies of rodent FASD models suggest that interference with hypothalamic-pituitary-adrenal (HPA) axis structure and/or function may be the basis for some of the prenatal alcohol (ethanol) exposure (PAE)-induced behavioral abnormalities. Included among the previous investigations are those illustrating that maternal alcohol treatment limited to very early stages of pregnancy (i.e., gestational day [GD]7 in mice; equivalent to the third week post-fertilization in humans) can cause structural abnormalities in areas such as the hypothalamus, pituitary gland, and other forebrain regions integral to controlling stress and behavioral responses. The current investigation was designed to further examine the sequelae of prenatal alcohol insult at this early time period, with particular attention to HPA axis-associated functional changes in adult mice. The results of this study reveal that GD7 PAE in mice causes HPA axis dysfunction, with males and females showing elevated corticosterone (CORT) and adrenocorticotropic hormone (ACTH) levels, respectively, following a 15-min restraint stress exposure. Males also showed elevated CORT levels following an acute alcohol injection of 2.0 g/kg, while females displayed blunted ACTH levels. Furthermore, analysis showed that anxiety-like behavior was decreased after GD7 PAE in female mice, but was increased in male mice. Collectively, the results of this study show that early gestational alcohol exposure in mice alters long-term HPA axis activity and behavior in a sexually dimorphic manner. Copyright © 2015 Elsevier Inc. All rights reserved.

Stress assessment in captive greylag geese (Anser anser).

PubMed

Scheiber, I B R; Sterenborg, M; Komdeur, J

2015-05-01

Chronic stress--or, more appropriately, "allostatic overload"--may be physiologically harmful and can cause death in the most severe cases. Animals in captivity are thought to be particularly vulnerable to allostatic overload due to artificial housing and group makeup. Here we attempted to determine if captive greylag geese (Anser anser), housed lifelong in captivity, showed elevated levels of immunoreactive corticosterone metabolites (CORT) and ectoparasites in dropping samples as well as some hematological parameters (hematocrit, packed cell volume, total white blood cell count [TWBC], and heterophil:lymphocyte ratio [H:L]). All of these have been measured as indicators of chronic stress. Furthermore, we correlated the various stress parameters within individuals. Captive geese showed elevated values of CORT and ectoparasites relative to a wild population sampled in the vicinity of the area where the captive flock is held. The elevated levels, however, were by no means at a pathological level and fall well into the range of other published values in wild greylag geese. We found no correlations between any of the variables measured from droppings with any of the ones collected from blood. Among the blood parameters, only the H:L negatively correlated with TWBC. We examine the problem of inferring allostatic overload when measuring only 1 stress parameter, as there is no consistency between various measurements taken. We discuss the different aspects of each of the parameters measured and the extensive individual variation in response to stress as well as the timing at which different systems respond to a stressor and what is actually measured at the time of data collection. We conclude that measuring only 1 stress parameter often is insufficient to evaluate the well-being of both wild and captively housed animals and that collecting behavioral data on stress might be a suitable addition.

Environmental Enrichment Increases Glucocorticoid Receptors and Decreases GluA2 and Protein Kinase M Zeta (PKMζ) Trafficking During Chronic Stress: A Protective Mechanism?

PubMed Central

Zanca, Roseanna M.; Braren, Stephen H.; Maloney, Brigid; Schrott, Lisa M.; Luine, Victoria N.; Serrano, Peter A.

2015-01-01

Environmental enrichment (EE) housing paradigms have long been shown beneficial for brain function involving neural growth and activity, learning and memory capacity, and for developing stress resiliency. The expression of the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor subunit GluA2, which is important for synaptic plasticity and memory, is increased with corticosterone (CORT), undermining synaptic plasticity and memory. Thus, we determined the effect of EE and stress on modulating GluA2 expression in Sprague-Dawley male rats. Several markers were evaluated which include: plasma CORT, the glucocorticoid receptor (GR), GluA2, and the atypical protein kinase M zeta (PKMζ). For 1 week standard-(ST) or EE-housed animals were treated with one of the following four conditions: (1) no stress; (2) acute stress (forced swim test, FST; on day 7); (3) chronic restraint stress (6 h/day for 7 days); and (4) chronic + acute stress (restraint stress 6 h/day for 7 days + FST on day 7). Hippocampi were collected on day 7. Our results show that EE animals had reduced time immobile on the FST across all conditions. After chronic + acute stress EE animals showed increased GR levels with no change in synaptic GluA2/PKMζ. ST-housed animals showed the reverse pattern with decreased GR levels and a significant increase in synaptic GluA2/PKMζ. These results suggest that EE produces an adaptive response to chronic stress allowing for increased GR levels, which lowers neuronal excitability reducing GluA2/PKMζ trafficking. We discuss this EE adaptive response to stress as a potential underlying mechanism that is protective for retaining synaptic plasticity and memory function. PMID:26617502

Maternal postpartum learned helplessness (LH) affects maternal care by dams and responses to the LH test in adolescent offspring.

PubMed

Kurata, Akiko; Morinobu, Shigeru; Fuchikami, Manabu; Yamamoto, Shigeto; Yamawaki, Shigeto

2009-06-01

It is known that the early environment affects the mental development of rodent and human offspring. However, it is not known specifically whether a postpartum depressive state influences the depressive state in offspring. Using learned helplessness (LH) in rats as an animal model of depression, we examined the influence of maternal postpartum LH on responses to the LH test of offspring. Dam rats were judged as LH or non-helpless (nLH) on postnatal days (PN) 2-3, and maternal behavior was recorded during PN2-14. On PN 45-46, offspring were subjected to the LH test. Plasma corticosterone (CORT) levels, hippocampal levels of glucocorticoid receptor (GR) and brain-derived neurotrophic factor (BDNF) mRNA were measured before and after the LH test in offspring. Active nursing in LH dams was significantly lower than that in nLH dams. Susceptibility to LH in the offspring of LH dams was significantly higher than in those of nLH dams, and was negatively correlated with active nursing by LH dams. The GR mRNA levels before and after the LH test were lower in the offspring of LH dams than in those of nLH dams, and the reduced basal GR mRNA and protein might have resulted in the higher CORT response after the LH test. There was no significant difference in BDNF mRNA in the offspring of LH and nLH dams. These findings suggest that early postpartum LH decreased active nursing and increased depression-like behavior in the adolescent offspring via dysfunction of the hypothalamic-pituitary-adrenal axis.

Effects of 𝛽-Hydroxy-𝛽-methylbutyrate-free Acid Supplementation on Strength, Power and Hormonal Adaptations Following Resistance Training

PubMed Central

Asadi, Abbas; Arazi, Hamid

2017-01-01

Background: β-Hydroxy-β-methylbutyrate-free acid (HMB-FA) has been ingested prior to exercise to reduce muscle damage, however the effects of HMB-FA supplementation on hormonal, strength and power adaptation are unclear. Methods: Sixteen healthy men were matched and randomized into two groups and performed six-week resistance training while supplementing with either HMB-FA or placebo (3 g per day). The subjects were evaluated for 1 repetition maximum (1RM) bench press and leg press and vertical jump (VJ) prior to and after training intervention. In addition, blood samples were obtained before and after resistance training to evaluate resting growth hormone (GH), insulin like growth factor 1 (IGF-1), testosterone (TEST), cortisol (CORT), and adrenocorticotropic hormone (ACTH) responses. The HMB-FA supplementation group showed greater gains compared with the placebo group in peak power (effect size ES = 0.26 vs. 0.01) and 1RM leg press (ES = 1.52 vs. 0.96). In addition, the HMB-FA supplementation group indicated greater decrements in ACTH and CORT responses to training in comparison to the placebo group (p < 0.05). Likewise, in GH (ES = 1.41 vs. 0.12) and IGF-1 (ES = 0.83 vs. 0.41), the HMB-FA indicated greater training effects when compared with the placebo group. Conclusions: These findings provide further support for the potential anabolic benefits associated with HMB-FA supplementation. PMID:29207472

Effect of tribulus terrestris saponins on behavior and neuroendocrine in chronic mild stress depression rats.

PubMed

Wang, Zhe; Zhang, Dongdong; Hui, Shan; Zhang, Yingjin; Hu, Suiyu

2013-04-01

To observe the effect of tribulus terrestris saponins (TTS) on behavior and neuroendocrine of chronic mild stress (CMS) depression rats. Thirty male Sprague-Dawley rats were randomly allocated to six groups: vehicle group, CMS group, CMS + fluoxetine group and CMS + TTS of low-dosage (0.375 g/kg), medium-dosage (0.75 g/kg) and high-dosage (2.25 g/kg) groups. All rats except the vehicle group singly housed and exposed an unpredicted sequence of mild stressors. The behavior of rats was detected by open-field test (OFT) and sucrose preference test (SPT). The concentration of corticotropin-releasing factor (CRF) and adrenocorticotropic hormone (ACTH) in serum of the rats were detected by radioimmunoassay. The concentration of cortisol (CORT) in serum was detected by enzyme immunoassay. CMS procedure not only significantly decreased the scores of crossing, rears and grooming in OFT and the sucrose preference in SPT (all P < 0.01), but also markedly increased serum CRH and CORT levels (both P < 0.05). Treatment with TTS (0.75 and 2.25 g/kg) could significantly prevent all of these abnormalities induced by CMS (P < 0.05, P < 0.01). CMS can affect rat behavior and neuroendocrine and cause depression. TTS has the antagonism on CMS and produce antidepressive effects.

Molecular Basis for Glucocorticoid Induction of the Krüppel-Like Factor 9 Gene in Hippocampal Neurons

PubMed Central

Bagamasbad, Pia; Ziera, Tim; Borden, Steffen A.; Bonett, Ronald M.; Rozeboom, Aaron M.; Seasholtz, Audrey

2012-01-01

Stress has complex effects on hippocampal structure and function, which consequently affects learning and memory. These effects are mediated in part by circulating glucocorticoids (GC) acting via the intracellular GC receptor (GR) and mineralocorticoid receptor (MR). Here, we investigated GC regulation of Krüppel-like factor 9 (KLF9), a transcription factor implicated in neuronal development and plasticity. Injection of corticosterone (CORT) in postnatal d 6 and 30 mice increased Klf9 mRNA and heteronuclear RNA by 1 h in the hippocampal region. Treatment of the mouse hippocampal cell line HT-22 with CORT caused a time- and dose-dependent increase in Klf9 mRNA. The CORT induction of Klf9 was resistant to protein synthesis inhibition, suggesting that Klf9 is a direct CORT-response gene. In support of this hypothesis, we identified two GR/MR response elements (GRE/MRE) located −6.1 and −5.3 kb relative to the transcription start site, and we verified their functionality by enhancer-reporter, gel shift, and chromatin immunoprecipitation assays. The −5.3-kb GRE/MRE is largely conserved across tetrapods, but conserved orthologs of the −6.1-kb GRE/MRE were only detected in therian mammals. GC treatment caused recruitment of the GR, histone hyperacetylation, and nucleosome removal at Klf9 upstream regions. Our findings support a predominant role for GR, with a minor contribution of MR, in the direct regulation of Klf9 acting via two GRE/MRE located in the 5′-flanking region of the gene. KLF9 may play a key role in GC actions on hippocampal development and plasticity. PMID:22962255

Stressor and Glucocorticoid-Dependent Induction of the Immediate Early Gene Krüppel-Like Factor 9: Implications for Neural Development and Plasticity

PubMed Central

Bonett, Ronald M.; Hu, Fang; Bagamasbad, Pia; Denver, Robert J.

2009-01-01

Krüppel-like factor 9 (KLF9) is a thyroid hormone-induced, immediate early gene implicated in neural development in vertebrates. We analyzed stressor and glucocorticoid (GC)-dependent regulation of KLF9 expression in the brain of the frog Xenopus laevis, and investigated a possible role for KLF9 in neuronal differentiation. Exposure to shaking/confinement stressor increased plasma corticosterone (CORT) concentration, and KLF9 immunoreactivity in several brain regions, which included the medial amygdala and bed nucleus of the stria terminalis, anterior preoptic area (homologous to the mammalian paraventricular nucleus), and optic tectum (homologous to the mammalian superior colliculus). The stressor-induced KLF9 mRNA expression in the brain was blocked by pretreatment with the GC receptor antagonist RU486, or mimicked by injection of CORT. Treatment with CORT also caused a rapid and dose-dependent increase in KLF9 mRNA in X. laevis XTC-2 cells that was resistant to inhibition of protein synthesis. The action of CORT on KLF9 expression in XTC-2 cells was blocked by RU486, but not by the mineralocorticoid receptor antagonist spironolactone. To test for functional consequences of up-regulation of KLF9, we introduced a KLF9 expression plasmid into living tadpole brain by electroporation-mediated gene transfer. Forced expression of KLF9 in tadpole brain caused an increase in Golgi-stained cells, reflective of neuronal differentiation/maturation. Our results support that KLF9 is a direct, GC receptor target gene that is induced by stress, and functions as an intermediary in the actions of GCs on brain gene expression and neuronal structure. PMID:19036875

Maternal postpartum corticosterone and fluoxetine differentially affect adult male and female offspring on anxiety-like behavior, stress reactivity, and hippocampal neurogenesis.

PubMed

Gobinath, Aarthi R; Workman, Joanna L; Chow, Carmen; Lieblich, Stephanie E; Galea, Liisa A M

2016-02-01

Postpartum depression (PPD) affects approximately 15% of mothers, disrupts maternal care, and can represent a form of early life adversity for the developing offspring. Intriguingly, male and female offspring are differentially vulnerable to the effects of PPD. Antidepressants, such as fluoxetine, are commonly prescribed for treating PPD. However, fluoxetine can reach offspring via breast milk, raising serious concerns regarding the long-term consequences of infant exposure to fluoxetine. The goal of this study was to examine the long-term effects of maternal postpartum corticosterone (CORT, a model of postpartum stress/depression) and concurrent maternal postpartum fluoxetine on behavioral, endocrine, and neural measures in adult male and female offspring. Female Sprague-Dawley dams were treated daily with either CORT or oil and fluoxetine or saline from postnatal days 2-23, and offspring were weaned and left undisturbed until adulthood. Here we show that maternal postpartum fluoxetine increased anxiety-like behavior and impaired hypothalamic-pituitary-adrenal (HPA) axis negative feedback in adult male, but not female, offspring. Furthermore, maternal postpartum fluoxetine increased the density of immature neurons (doublecortin-expressing) in the hippocampus of adult male offspring but decreased the density of immature neurons in adult female offspring. Maternal postpartum CORT blunted HPA axis negative feedback in males and tended to increase density of immature neurons in males but decreased it in females. These results indicate that maternal postpartum CORT and fluoxetine can have long-lasting effects on anxiety-like behavior, HPA axis negative feedback, and adult hippocampal neurogenesis and that adult male and female offspring are differentially affected by these maternal manipulations. Copyright © 2015 Elsevier Ltd. All rights reserved.

Profiling Coping Strategies in Male and Female Rats: Potential neurobehavioral markers of increased resilience to depressive symptoms

PubMed Central

Kent, Molly; Bardi, Massimo; Hazelgrove, Ashley; Sewell, Kaitlyn; Kirk, Emily; Thompson, Brooke; Trexler, Kristen; Terhune-Cotter, Brennan; Lambert, Kelly

2018-01-01

Coping strategies have been associated with differential stress responsivity, perhaps providing a valuable neurobiological marker for susceptibility to the emergence of depressogenic symptoms or vulnerability to other anxiety-related disorders. Rats profiled with a flexible coping phenotype, for example, exhibit increased neurobiological markers of emotional regulation compared to active and passive copers (Bardi et al., 2012; Lambert et al., 2014). In the current study, responses of male and female rats to prediction errors in a spatial foraging task (dry land maze; DLM) were examined after animals were exposed to chronic unpredictable stress (CUS). Brains were processed following the DLM training/assessment for fos-activation patterns and several measures of neuroplasticity in relevant areas. Behavioral responses observed during both the CUS and DLM phases of testing suggested that males and females employ different means of gathering information such as increased ambulatory exploration in males and rear responses in females. Fecal samples collected during baseline and following CUS swim exposure revealed higher corticosterone (CORT) in active copers, whereas flexible copers had higher dehydroepiandrosterone (DHEA) and DHEA/CORT ratios, both indications of enhanced emotional regulation. Focusing on the neural analysis, flexible copers exhibited fewer fos-immunoreactive cells in the basolateral amygdala and a trend toward lower activation in the insula while encountering the prediction error associated with the DLM probe trial. Coping profiles also differentially influenced markers of neuroplasticity; specifically, flexible copers exhibited higher levels nestin-immunoreactivity (ir). Further, less hippocampal glucocorticoid receptor-ir was observed in the flexible copers than the active and passive copers. In sum, flexible coping rats exhibited evidence of emotional resilience as indicated by several neurobiological measures; however, despite increased rates of depression and related symptoms reported in human females, sex effects weren’t as pervasive as coping strategy profiles in the analysis of neurobiological markers employed in the current study. PMID:28755980

The FKBP5 Gene Affects Alcohol Drinking in Knockout Mice and Is Implicated in Alcohol Drinking in Humans.

PubMed

Qiu, Bin; Luczak, Susan E; Wall, Tamara L; Kirchhoff, Aaron M; Xu, Yuxue; Eng, Mimy Y; Stewart, Robert B; Shou, Weinian; Boehm, Stephen L; Chester, Julia A; Yong, Weidong; Liang, Tiebing

2016-08-05

FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21-26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

Inhibition of the CRF1 receptor influences the activity of antidepressant drugs in the forced swim test in rats.

PubMed

Wróbel, Andrzej; Serefko, Anna; Szopa, Aleksandra; Rojek, Karol; Poleszak, Ewa; Skalicka-Woźniak, Krystyna; Dudka, Jarosław

2017-08-01

Hyperactivity of the hypothalamic-pituitary-adrenal axis (HPA) and impairment of the central corticotropin-releasing factor (CRF) system are factors in the pathogenesis of depression. Though several antagonists of the CRF 1 receptor were effective in the recognized behavioral tests for antidepressant activity, there is still little information on the potential interactions between CRF 1 receptor inhibitors and conventional antidepressant therapy. The aim of our study was to assess the influence of SN003, a CRF 1 receptor blocker, on the activity of imipramine and fluoxetine in the forced swim test (FST) in rats which presented some signs of depression. The experiments were carried out on female Wistar rats subjected to 14-day subcutaneous corticosterone (CORT) administration (20 mg/kg/day). The antidepressant-like effect was determined by the FST and the CRF levels in the hypothalamus, amygdala, and peripheral blood were measured by a high-sensitivity immunoenzymatic test. SN003 (0.5 mg/kg) potentiated the antidepressant-like effect of imipramine (15 mg/kg) and fluoxetine (7.5 mg/kg). Moreover, the co-administration of the tested agents abolished CORT-induced increase in CRF levels in the examined biological material more profoundly than monotherapy. Our present findings give further evidence that the blockage of CRF action may be useful in the treatment of mood disorders. The concurrent use of well-known antidepressants with CRF 1 receptor antagonists could be beneficial in terms of safety, since it requires lower doses of the applied agents.

Stress-induced changes of neurosteroid profiles in rat brain and plasma under immobilized condition.

PubMed

Park, Myeong Hyeon; Rehman, Shaheed Ur; Kim, In Sook; Choi, Min Sun; Yoo, Hye Hyun

2017-05-10

In this study, various neurosteroids in brain and plasma were simultaneously determined using liquid chromatography-tandem mass spectrometry and their profile changes in a stress-induced rats were investigated. The investigated neurosteroids are as follows: progesterone (P4), 5α-dihydroprogesterone (5α-DHP), 5β-dihydroprogesterone, estrone, androstenedione (AE), cortisol, cortisone, corticosterone (CORT), dehydroepiandrosterone (DHEA), pregnanolone (3α,5β-THP), allopregnanolone (ALLO), 11-deoxycorticosterone (DOC), 11-deoxycortisol, pregnenolone (PREG), and 5α/5β-tetrahydrodeoxycorticosterone (5α/5β-THDOC). Brain and plasma samples were processed using solid-phase extraction with methanol and acetic acid (99:1), and derivatized with a hydroxylamine reagent. Separation was achieved within 13min at a flow rate of 0.4mL/min with a C18 column (3.0×50mm, 2.7μm). The triple quadrupole mass spectrometer was operated in the positive electrospray ionization mode. Using this method, the neurosteroid level variation was quantitated and investigated in the brain and plasma upon immobilization stress in rats. As a result, AE, CORT, DOC, P4, 5α-DHP, 5α/5β-THDOC, DHEA, 3α,5β-THP, ALLO, and PREG levels were significantly altered in both the brain and plasma samples when stress was induced. These findings demonstrated that stress leads to the alteration of the GABAergic neurosteroid profile. The present results will be helpful for furthering an understanding of the role of neurosteroids in stressed conditions. Copyright © 2017 Elsevier B.V. All rights reserved.

Maternal glucocorticoid elevation and associated blood metabonome changes might be involved in metabolic programming of intrauterine growth retardation in rats exposed to caffeine prenatally

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kou, Hao; Liu, Yansong; Liang, Gai

Our previous studies demonstrated that prenatal caffeine exposure causes intrauterine growth retardation (IUGR), fetuses are over-exposed to high levels of maternal glucocorticoids (GC), and intrauterine metabolic programming and associated metabonome alteration that may be GC-mediated. However, whether maternal metabonomes would be altered and relevant metabolite variations might mediate the development of IUGR remained unknown. In the present studies, we examined the dose- and time-effects of caffeine on maternal metabonome, and tried to clarify the potential roles of maternal GCs and metabonome changes in the metabolic programming of caffeine-induced IUGR. Pregnant rats were treated with caffeine (0, 20, 60 or 180more » mg/kg · d) from gestational days (GD) 11 to 20, or 180 mg/kg · d caffeine from GD9. Metabonomes of maternal plasma on GD20 in the dose–effect study and on GD11, 14 and 17 in the time–course study were analyzed by {sup 1}H nuclear magnetic resonance spectroscopy, respectively. Caffeine administration reduced maternal weight gains and elevated both maternal and fetal corticosterone (CORT) levels. A negative correlation between maternal/fetal CORT levels and fetal bodyweight was observed. The maternal metabonome alterations included attenuated metabolism of carbohydrates, enhanced lipolysis and protein breakdown, and amino acid accumulation, suggesting GC-associated metabolic effects. GC-associated metabolite variations (α/β-glucoses, high density lipoprotein-cholesterol, β-hydroxybutyrate) were observed early following caffeine administration. In conclusion, prenatal caffeine exposure induced maternal GC elevation and metabonome alteration, and maternal GC and relevant discriminatory metabolites might be involved in the metabolic programming of caffeine-induced IUGR. - Highlights: • Prenatal caffeine exposure elevated maternal blood glucocorticoid levels. • Prenatal caffeine exposure altered maternal blood metabonomes. • Maternal metabonome alterations were associated with glucocorticoid elevation. • Maternal metabonomes were altered at early stage after caffeine exposure. • Maternal glucocorticoid and associated metabolites may be involved in fetal programming.« less

The identification and characteristics of Echinoparyphium rubrum (Cort. 1914) new comb. (Trematoda, Echinostomatidae) based on experimental evidence of the life cycle

USGS Publications Warehouse

Kanev, I.; Sorensen, R.; Sterner, M.; Cole, Rebecca A.; Fried, B.

1998-01-01

The life cycle of Echinoparyphium rubrum (Cort, 1914) comb. n. has been completed experimentally. All of the developmental stages egg, miracidium, sporocyst, mother and daughter rediae, cercaria, metacercaria, and adult were examined and described. The miracidia infected freshwater snails of the genus Physa , P. gyrina and P. occidentalis. Attempts to infect snails of the genera Lymnaea, L. auricularis, L. peregra, L. truncatula and Bulinus, B. truncatus failed. Cercariae infected various pulmonate and prosobranch freshwater snails, mussels, frogs, water turtles and planarians. The adults developed in the small intestine of birds and mammals. The identity and major characteristics of Echinoparyphium rubrum are discussed. Synonyms of E. rubrum are Cercaria rubra Cort, 1914; Cercaria biflexa Faust, 1917; Cercaria chisolenata Faust, 1918; Echinostoma callawayensis Barker et Noll, 1915; Echinostoma revolutum of Johnson (1920); Echinoparyphium elegans of Cannon (1938), of Bain and Trelfall (1977), of Mahoney and Trelfall (1977); and Echinoparyphium recurvatum of Jilek (1977), Harley (1972), Sankurathri and Holmes (1976). Comparisons are made between E. rubrum and its 43-collar-spined allies: E. flexum from North America, E. cinctum from Europe, E. dunni from Asia and E. elegans from Africa.

After 10 years, how do changes in asset ownership affect the Indicador Econômico Nacional?

PubMed

Ewerling, Fernanda; Barros, Aluísio J D

2017-03-02

Our main objective was to analyse how the evolution of household assets ownership affected the Indicador Econômico Nacional (IEN - National Wealth index) and to point out the most stable assets and which lost importance more quickly. We analysed the trend of the ownership of each IEN variable and the distribution of the households' scores. We calculated the correlation coefficients of each variable separately with the IEN score and the household income. We also evaluated how the changes of the score distribution over time affected the validity of the published reference cut-points. We used data from consortium surveys conducted every two years from 2002 to 2014 in the city of Pelotas, Brazil. An increase in the educational level of household heads and in the ownership of all IEN assets, except radio and telephone, was observed in the study period. In general, the correlation of the assets with the IEN scores decreased over time. There was an increase in the score, with a consequent increase in the quintiles cut-points, but the distance between these cut-points had no significant variation. Thus, the reference cut-points for Pelotas, quickly became outdated. Some assets showed greatly reduction on its importance for the indicator, and the reference cut-points became obsolete very quickly. It is essential for a standardized wealth (or asset) index with research purposes to be updated frequently, especially the cut-points of reference distribution. Analisar como a evolução temporal da posse de bens domésticos afetou o Indicador Econômico Nacional e como essas mudanças afetaram o poder discriminatório do indicador. Analisou-se a evolução temporal da posse de cada uma das variáveis do Indicador Econômico Nacional, bem como da distribuição do escore dos domicílios. Utilizamos dados de inquéritos populacionais realizados bienalmente no município de Pelotas, RS, de 2002 a 2014. Foi calculado o coeficiente de correlação de cada variável isoladamente com o escore do Indicador Econômico Nacional e com a renda familiar. Avaliamos também como a variação da distribuição do escore ao longo do tempo afetou a validade da utilização dos pontos de corte de referência publicados. Houve aumento da escolaridade dos chefes das famílias e da posse de todos os bens, exceto rádio e linha telefônica no período. A correlação dos bens com o Indicador Econômico Nacional reduziu com o tempo. O escore aumentou, com consequente incremento nos pontos de corte dos quintis, mas a distância entre os pontos não teve variação importante. Assim, os pontos de corte de referência publicados para Pelotas rapidamente ficaram desatualizados. Alguns bens perderam a capacidade discriminatória e os pontos de corte ficaram obsoletos rapidamente. É essencial um indicador de bens padronizado para uso em pesquisa, que seja atualizado com frequência, em especial os pontos de corte da distribuição de referência.

Characterization of estrogens, testosterone, and cortisol in normal bottlenose dolphin (Tursiops truncatus) pregnancy.

PubMed

Steinman, Karen J; Robeck, Todd R; O'Brien, Justine K

2016-01-15

The goal of this study was to describe profiles of serum estrogens, testosterone and cortisol during normal pregnancy in bottlenose dolphins. Predominant estrogens in all categories of dolphin sera pools during estrus and pregnancy (EARLY: Days 0-120; MID: Days 121-240; LATE: Days 241 to parturition; Day 0=day of conception) were estrone/estrone conjugates (E1-C) and estriol (E3). Serum samples collected throughout 101 normal pregnancies were analyzed for E1-C, E3, testosterone (T) and cortisol (CORT). E1-C was higher (P<0.05) during LATE compared to EARLY and MID, and higher (P<0.05) in nulliparous than multiparous females. E1-C concentrations were also inversely associated with maternal age (P=0.05). E3 was higher (P<0.05) in EARLY than MID and LATE, and higher overall for nulliparous than multiparous females, but concentrations were similar among gestational stages when parity was excluded from analyses. Analysis by indexed month post-conception (IMPC) demonstrated that E1-C increased from IMPC 9 and peaked at IMPC 11. E3 was significantly elevated during IMPC 1, decreased until IMPC 6 and peaked at IMPC 11. T increased (P<0.05) at IMPC 3 and continued to increase throughout gestation (P<0.05). CORT was higher (P<0.05) during LATE compared to EARLY and MID (P<0.05), peaked during IMPC 12, and was not affected by parity. Hormone profiles were not influenced by fetal sex. Copyright © 2015 Elsevier Inc. All rights reserved.

Sedimentary and structural patterns on the northern Santa Rosa-Cortes Ridge, southern California

USGS Publications Warehouse

Field, M.E.; Richmond, W.C.

1980-01-01

The Santa Rosa-Cortes Ridge is an 1800 m high, 180 km long feature lying approximately 90 km off the coast of southern California and directly south of the northern group of Channel Islands. Geophysical profiling and sampling cruises to the northern part of the ridge, an area of recent and future lease sales for petroleum development, provide a strong data base for interpretation of structural and sedimentary patterns and their relation to potential geologic hazards. The northern part of the ridge is a complexly folded and faulted northwest-trending anticlinorium composed mostly of lower and middle Miocene shale and mudstone. Erosional remnants of upper Miocene and Pliocene rocks unconformably overlie highly folded pre-upper Miocene strata. The major structure of the ridge developed almost continuously from Oligocene or early Miocene time to the end of the Tertiary; many small folds formed between post-late Miocene and pre-late Pleistocene time. Numerous small faults cut the rocks on the ridge top. Faults cut basement rocks on the west side of the ridge along the Ferrelo fault zone. Published data on historical epicenters and evidence of offsets on the seafloor from seismic reflection and side-scan profiles, including limited evidence of possible strike-slip movement along fault traces, indicate that the northern Santa Rosa-Cortes Ridge is tectonically active. The crest of the ridge was truncated as the result of repeated sea-level fluctuations in the Quaternary. A thin veneer of unconsolidated medium to fine sand, less than 3 m thick, mantles most of the ridge; locally in topographically low areas and on the upper flanks of the ridge, thickness exceeds 20 m. The meager sediment cover, coupled with available evidence of relatively strong currents flowing across the ridge top, indicate that the ridge is an area of nondeposition or winnowing of fine sediments. Modern sediments become thicker and finer-grained from the ridge top to the ridge flanks, suggesting active accretion in those areas. Slumps are present at various depths on the flanks, and it seems probable that the thicker deposits (> 20 m) of modern sediments on the upper flanks will be sites of future slumping. ?? 1980.

Schisandra chinensis produces the antidepressant-like effects in repeated corticosterone-induced mice via the BDNF/TrkB/CREB signaling pathway.

PubMed

Yan, Tingxu; Xu, Mengjie; Wan, Shutong; Wang, Mengshi; Wu, Bo; Xiao, Feng; Bi, Kaishun; Jia, Ying

2016-09-30

The present study aimed to examine the antidepressant-like effects and the possible mechanisms of Schisandra chinensis on depressive-like behavior induced by repeated corticosterone injections in mice. Here we evaluated the effect of an ethanol extract of the dried fruit of S. chinensis (EESC) on BDNF/TrkB/CREB signaling in the hippocampus and the prefrontal cortex. Three weeks of corticosterone injections in mice resulted in depressive-like behavior, as indicated by the significant decrease in sucrose consumption and increase the immobility time in the forced swim test, but without any influence on the locomotor activity. Further, there was a significant increase in serum corticosterone level and a significant downregulation of BDNF/TrkB/CREB signaling pathway in the hippocampus and prefrontal cortex in CORT-treated mice. Treatment of mice with EESC (600mg/kg) significantly ameliorated all the behavioral and biochemical changes induced by corticosterone. Moreover, pharmacological inhibition of BDNF signaling by K252a abolished entirely the antidepressant-like effect triggered by chronic EESC treatment. These results suggest that EESC produces an antidepressant-like effect in CORT-induced depression in mice, which is possibly mediated, at least in part, by rectifying the stress-based hypothalamic-pituitary-adrenal (HPA) axis dysfunction paradigm and upregulation of BDNF/TrkB/CREB signaling pathway. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Albeit nocturnal, rats subjected to traumatic brain injury do not differ in neurobehavioral performance whether tested during the day or night.

PubMed

Niesman, Peter J; Wei, Jiahui; LaPorte, Megan J; Carlson, Lauren J; Nassau, Kileigh L; Bao, Gina C; Cheng, Jeffrey P; de la Tremblaye, Patricia; Lajud, Naima; Bondi, Corina O; Kline, Anthony E

2018-02-05

Behavioral assessments in rats are overwhelmingly conducted during the day, albeit that is when they are least active. This incongruity may preclude optimal performance. Hence, the goal of this study was to determine if differences in neurobehavior exist in traumatic brain injured (TBI) rats when assessed during the day vs. night. The hypothesis was that the night group would perform better than the day group on all behavioral tasks. Anesthetized adult male rats received either a cortical impact or sham injury and then were randomly assigned to either Day (1:00-3:00p.m.) or Night (7:30-9:30p.m.) testing. Motor function (beam-balance/walk) was conducted on post-operative days 1-5 and cognitive performance (spatial learning) was assessed on days 14-18. Corticosterone (CORT) levels were quantified at 24h and 21days after TBI. No significant differences were revealed between the TBI rats tested during the Day vs. Night for motor or cognition (p's<0.05). CORT levels were higher in the Night-tested TBI and sham groups at 24h (p<0.05), but returned to baseline and were no longer different by day 21 (p>0.05), suggesting an initial, but transient, stress response that did not affect neurobehavioral outcome. These data suggest that the time rats are tested has no noticeable impact on their performance, which does not support the hypothesis. The finding validates the interpretations from numerous studies conducted when rats were tested during the day vs. their natural active period. Copyright © 2017 Elsevier B.V. All rights reserved.

[Inhibition of HCN1 channels by ketamine accounts for its antidepressant actions].

PubMed

Li, Jing; Chen, Feng-feng; Chen, Xiang-dong; Zhou, Cheng

2014-11-01

To investigate the roles of hyperolarization-actived cyclic nucleotide-gated channels 1 (HCN1) in antidepressant actions of ketamine (KET). Male HCN1 knock out (HCN1-/- ) and wildtype (HCN1+/+ ) C57BL6 mice (8-12 weeks, 20-25 g) were chosen. The depression model of mice was developed by continuously oral administration of low dosage of corticosterone (CORT). The immobility time in forced swimming tests (FST) was used to assess the depressive state of mice. Then the two genotype depressive mice were treated with single intraperitoneal injection of 5 mg/kg ketamine (KET group, n=7) or same volume of normal saline (NS group, n=7) respectively. After treatment, the immobility time at 30 min, 24 h and 7 d after the intraperitoneal injection of ketamine or normal saline in CORT-treated mice were compared. In addition, normal HCN1-/- and HCN1+/+ mice were intraperitoneally injected of BrdU and then treated with 5 mg/kg ketamine (KET group, n=5) or same volume of normal saline (NS group, n= 5) by single intraperitoneal injection. Each group was euthanized for immunohistochemical processing of 5-Bromo-2-deoxyuridine (BrdU)-labeled cells in hippocampus at 24 h after the intraperitoneal injection of saline or ketamine. The immobility time in FST of HCN1-/- mice was less than the HCN1+/+ mice before administration of CORT. It shows that the depressive state of HCN1-/- mice is less intensive than that of HCN1+/+ mice. And the immoblility time in both HCN1-/- and HCN1+/+ mice was increased after oral administration of low dose corticosterone, with an increase in depression. In addition, the comparisons were also made to the reduction of immobility time within 30 min, 24 h and 7 d. At any time point, the reduction of immobility time in HCN1+/+ KET group was higher than those in the other three groups (P<0. 05). Furthermore, there were no statistical significances among the three groups including HCN1-/- KET group, HCN1+/+ NS group, HCN1-/- NS group at any point. The number of newborn neurons were more in HCN1 mice than HCN1+/+ mice after the treatment of normal saline. Compared with the NS group, the number of neonatal neurons labeled by BrdU were increased after the intraperitoneal injection of ketamine in HCN1+/+ mice but not in HCN1-/- mice. Inhibition of HCN1 channels by ketamine accounts for its antidepressant actions.

Relationships between competitive wrestling success and neuroendocrine responses.

PubMed

Fry, Andrew C; Schilling, Brian K; Fleck, Steven J; Kraemer, William J

2011-01-01

Previous research on wrestling suggests winning wrestlers will have a greater increase in testosterone (Tes) than losing wrestlers, although the physiological mechanism is unknown. To determine the role of the sympathetic nervous system in this phenomenon, 12 male wrestlers from an National Collegiate Athletic Association Division I program wrestled 5 matches over a 2-day period. Serum samples were collected pre (Pre) and immediately postmatch (Post) for the determination of Tes, cortisol (Cort), Tes/Cort, and epinephrine (Epi). The subjects had a combined record of 34 wins, 31 losses, and 4 ties. Testosterone increased (p < 0.05) for both winners and losers, but the increase was greater for winners (X ± SE; nmol · L(-1); winners, pre = 16.4 ± 1.2, post = 23.2 ± 1.5; losers, pre = 14.8 ± 1.0, post = 19.4 ± 1.2). Cortisol and Epi increased similarly for both winners and losers, whereas the Tes/Cort ratio was unaltered at any time. Relative changes in the Epi response (%Δ) for losers were correlated to %ΔTes (r = 0.91), whereas winners did not exhibit similar relationships (r = 0.09). These data suggest that winning wrestlers may use a different regulatory mechanism for their acute Tes responses than losers who appear to depend on sympathetic regulation. Additionally, these data from humans support the biosocial theory of status and the challenge hypothesis developed for competing males in other species.

Benefits of family reunions: social support in secondary greylag goose families.

PubMed

Scheiber, Isabella B R; Kotrschal, Kurt; Weiss, Brigitte M

2009-01-01

Social interactions are among the most potent stressors. However, social allies may diminish stress, increase success in agonistic encounters and ease access to resources. We studied the role of social support as a major mechanism for individual stress management in families of free-ranging greylag geese (Anser anser). Greylag geese are long-term monogamous, live in a female-bonded social system, and fledged offspring stay with their parents until the next breeding season ('primary families'). Should parents then fail to fledge young, subadults might rejoin them in summer after molt is completed ('secondary families'). We have previously shown that primary greylag goose families reap benefits from active social support in agonistic encounters, and also excrete lower levels of immuno-reactive corticosterone metabolites (CORT, 'passive social support'). Here we investigated how far active and passive social support continues in secondary goose families. Although we found that active support in agonistic encounters was almost absent in secondary families, subadult male geese won an increased number of agonistic encounters due to the mere presence of their secondary family. Particularly adult and subadult females benefited from passive social support through decreased CORT, whereas males did not. Decrease in the hormonal stress response during challenging situations, induced by social allies, may help the females' long-term energy management, thereby improving the odds for successful future reproduction. We discuss whether joining a secondary family may be an alternative tactic for young geese towards optimizing their start into a complex social life.

Hormetic effects by exercise on hippocampal neurogenesis with glucocorticoid signaling

PubMed Central

Okamoto, Masahiro; Yamamura, Yuhei; Liu, Yu-Fan; Min-Chul, Lee; Matsui, Takashi; Shima, Takeru; Soya, Mariko; Takahashi, Kanako; Soya, Shingo; McEwen, Bruce S.; Soya, Hideaki

2015-01-01

Abstract Exercise enhances adult hippocampal neurogenesis (AHN), although the exact nature of how this happens remains controversial. The beneficial effects of exercise vary depending upon the exercise condition, especially intensity. Most animal studies, however, have used wheel running, which only evaluates running distance (exercise volume) and does not consider intensity. In our rat model, we have found that exercise-induced neurogenesis varies depending on the intensity of the exercise and have found that exercise-enhanced neurogenesis is more pronounced with mild exercise than with moderate and/or intense exercise. This may be due, at least in part, to increased glucocorticoid (CORT) secretion. To test this hypothesis, we used our special exercise model in mice, with and without a stress response, based on the lactate threshold (LT) in which moderate exercise above the LT increases lactate and adrenocorticotropic hormone (ACTH) release, while mild exercise does not. Adult male C57BL/6J mice were subjected to two weeks of exercise training and AHN was measured with a 5-Bromo-2-deoxyuridine (BrdU) pre-injection and immunohistochemistry. The role of glucocorticoid signaling was examined using intrapertioneal injections of antagonists for the glucocorticoid receptor (GR), mifepristone, and the mineralocorticoid receptor (MR), spironolactone. We found that, while mild exercise increased AHN without elevating CORT blood levels, both MR and GR antagonists abolished mild-exercise-induced AHN, but did not affect AHN under intense exercise. This suggests a facilitative, permissive role of glucocorticoid and mineralocorticoid receptors in AHN during mild exercise (234/250)

Benefits of family reunions: Social support in secondary greylag goose families

PubMed Central

Scheiber, Isabella B.R.; Kotrschal, Kurt; Weiß, Brigitte M.

2011-01-01

Social interactions are among the most potent stressors. However, social allies may diminish stress, increase success in agonistic encounters and ease access to resources. We studied the role of social support as a major mechanism for individual stress management in families of free-ranging greylag geese (Anser anser). Greylag geese are long-term monogamous, live in a female-bonded social system, and fledged offspring stay with their parents until the next breeding season (‘primary families’). Should parents then fail to fledge young, subadults might rejoin them in summer after molt is completed (‘secondary families’). We have previously shown that primary greylag goose families reap benefits from active social support in agonistic encounters, and also excrete lower levels of immuno-reactive corticosterone metabolites (CORT, ‘passive social support’). Here we investigated how far active and passive social support continues in secondary goose families. Although we found that active support in agonistic encounters was almost absent in secondary families, subadult male geese won an increased number of agonistic encounters due to the mere presence of their secondary family. Particularly adult and subadult females benefited from passive social support through decreased CORT, whereas males did not. Decrease in the hormonal stress response during challenging situations, induced by social allies, may help the females’ long-term energy management, thereby improving the odds for successful future reproduction. We discuss whether joining a secondary family may be an alternative tactic for young geese towards optimizing their start into a complex social life. PMID:18848947

Effects of Maternally-Transferred Methylmercury on Stress Physiology in Northern Water Snake (Nerodia sipedon) Neonates.

PubMed

Cusaac, J Patrick W; Kremer, Victoria; Wright, Raymond; Henry, Cassandra; Otter, Ryan R; Bailey, Frank C

2016-06-01

Biomagnification of methylmercury in aquatic systems can cause elevated tissue mercury (Hg) and physiological stress in top predators. Mercury is known to affect stress hormone levels in mammals, birds and fish. In this study, the effects of maternally-transferred methylmercury on the stress physiology of Northern Water Snake (Nerodia sipedon) neonates were tested. Gravid females were dosed via force-fed capsules during late gestation with 0, 0.01, or 10 µg methylmercury per gram of body mass. Plasma corticosterone levels and leukocyte differentials were analyzed in baseline and confinement-stressed neonates from all dose levels. Neither Hg nor confinement stress had a significant effect on leukocyte differentials nor was Hg related to corticosterone levels. However, stress group neonates showed lower heterophil/lymphocyte ratios and this study was the first to show that neonate N. sipedon can upregulate CORT in response to stress. These results indicate that N. sipedon may be somewhat tolerant to Hg contamination.

Public Libraries

ERIC Educational Resources Information Center

Library Journal, 1972

1972-01-01

Building data is given for the following public libraries: New York, New York; Blue Island, Illinois; Corte Madera, California; Muskogee, Oklahoma: Charlotte, North Carolina; Washington, D.C.; Houston, Texas; Albermarle, North Carolina; Spokane, Washington; and Hemet, California. (Author/NH)

Acute stress enhances learning and memory by activating acid-sensing ion channels in rats.

PubMed

Ye, Shunjie; Yang, Rong; Xiong, Qiuju; Yang, Youhua; Zhou, Lianying; Gong, Yeli; Li, Changlei; Ding, Zhenhan; Ye, Guohai; Xiong, Zhe

2018-04-15

Acute stress has been shown to enhance learning and memory ability, predominantly through the action of corticosteroid stress hormones. However, the valuable targets for promoting learning and memory induced by acute stress and the underlying molecular mechanisms remain unclear. Acid-sensing ion channels (ASICs) play an important role in central neuronal systems and involves in depression, synaptic plasticity and learning and memory. In the current study, we used a combination of electrophysiological and behavioral approaches in an effort to explore the effects of acute stress on ASICs. We found that corticosterone (CORT) induced by acute stress caused a potentiation of ASICs current via glucocorticoid receptors (GRs) not mineralocorticoid receptors (MRs). Meanwhile, CORT did not produce an increase of ASICs current by pretreated with GF109203X, an antagonist of protein kinase C (PKC), whereas CORT did result in a markedly enhancement of ASICs current by bryostatin 1, an agonist of PKC, suggesting that potentiation of ASICs function may be depended on PKC activating. More importantly, an antagonist of ASICs, amiloride (10 μM) reduced the performance of learning and memory induced by acute stress, which is further suggesting that ASICs as the key components involves in cognitive processes induced by acute stress. These results indicate that acute stress causes the enhancement of ASICs function by activating PKC signaling pathway, which leads to potentiated learning and memory. Copyright © 2018 Elsevier Inc. All rights reserved.

Defining family elements in adolescence.

PubMed

Băcean, Oana Codruţa Miloicov; Vlaicu, Brigitha

2012-01-01

The family has a permanent partner role on adolescents till adult stage. The adolescent builds up his own identity based on the affiliation to his family, but he gets away from his family for the need of leading his own life and finding his place in society. The adolescent sample was made up of 2908 college students from Timis County, aged between 15-19 years, 51.5% girls and 48.5% boys. The working method was the populational transversal study based on anonymous self-administration of the investigation questionnaire CORT 2004 about the risky comportment in teenagers, in a CNCSIS research project. The study results high lighten the predominance of family organized affiliation, 78.9% living with family, 88.6%; the medium study level of 63.7% of mothers and 59.1% of fathers; the satisfaction towards family members, 71.7%; satisfaction towards family's financial level, 61.2%. In this way is underlined the role of identity development in adolescents.

Comparative Evaluation of the Implementation of the Deficit Reduction Act within the Department of Defense.

DTIC Science & Technology

1986-06-01

critical pieces o Con dressionSal le islat ion crece- in- thie Deficit e u A c t, i wci o c u se o n thie efforts of Con ;res3 to sr control over federal...personnel turnover thiat cz 50,- iii .~ areas -,er six -.:onthi -eriod. .ost of t.i2 critical andt -,anual Jo.bs are h.el.d )y personnel in ~. Jra Jes wno...lsz u Per: orm a critical f o"Ition of cort ification of o~ :.tr 1’. or 3,erv~c; are nba -nr~ ZJ tircirtific~tib1 1 -t or not, or cw ,-r n r r L) all

Impact of Psychological Stress on Pain Perception in an Animal Model of Endometriosis.

PubMed

Hernandez, Siomara; Cruz, Myrella L; Seguinot, Inevy I; Torres-Reveron, Annelyn; Appleyard, Caroline B

2017-10-01

Pain in patients with endometriosis is considered a significant source of stress but does not always correlate with severity of the condition. We have demonstrated that stress can worsen endometriosis in an animal model. Here, we tested the impact of a psychological stress protocol on pain thresholds and pain receptors. Endometriosis was induced in female rats by suturing uterine horn tissue next to the intestinal mesentery. Sham rats had sutures only. Rats were exposed to water avoidance stress for 7 consecutive days or handled for 5 minutes (no stress). Fecal pellets and serum corticosterone (CORT) levels were measured as an index of anxiety. Pain perception was assessed using hot plate and Von Frey tests. Substance P, enkephalin, endomorphin-2, Mu opioid receptor (MOR), and neurokinin-1 receptor expression in the spinal cord were measured by immunohistochemistry. Fecal pellets and CORT were significantly higher in the endo-stress (ES) group than endo-no stress (ENS; P < .01) and sham-no stress groups (SNS; P < .01). The ES rats had more colonic damage ( P < .001 vs SNS; P < .05 vs ENS), vesicle mast cell infiltration ( P < .01 vs ENS), and more severe vesicles than ENS. The ES developed significant hyperalgesia ( P < .05) but stress reversed the allodynic effect caused by endo ( P < .001). The MOR expression was significantly reduced in ENS versus SNS ( P < .05) and more enkephalin expression was found in endo groups. Animals subjected to stress develop more severe symptoms but interestingly stress seems to have beneficial effects on abdominal allodynia, which could be a consequence of the stress-induced analgesia phenomenon.

Vicarious social defeat stress: Bridging the gap between physical and emotional stress.

PubMed

Sial, Omar K; Warren, Brandon L; Alcantara, Lyonna F; Parise, Eric M; Bolaños-Guzmán, Carlos A

2016-01-30

Animal models capable of differentiating the neurobiological intricacies between physical and emotional stress are scarce. Current models rely primarily on physical stressors (e.g., chronic unpredictable or mild stress, social defeat, learned helplessness), and neglect the impact of psychological stress alone. This is surprising given extensive evidence that a traumatic event needs not be directly experienced to produce enduring perturbations on an individual's health and psychological well-being. Post-traumatic stress disorder (PTSD), a highly debilitating neuropsychiatric disorder characterized by intense fear of trauma-related stimuli, often occurs in individuals that have only witnessed a traumatic event. By modifying the chronic social defeat stress (CSDS) paradigm to include a witness component (witnessing the social defeat of another mouse), we demonstrate a novel behavioral paradigm capable of inducing a robust behavioral syndrome reminiscent of PTSD in emotionally stressed adult mice. We describe the vicarious social defeat stress (VSDS) model that is capable of inducing a host of behavioral deficits that include social avoidance and other depressive- and anxiety-like phenotypes in adult male mice. VSDS exposure induces weight loss and spike in serum corticosterone (CORT) levels. A month after stress, these mice retain the social avoidant phenotype and have an increased CORT response when exposed to subsequent stress. The VSDS is a novel paradigm capable of inducing emotional stress by isolating physical stress/confrontation in mice. The VSDS model can be used to study the short- and long-term neurobiological consequences of exposure to emotional stress in mice. Copyright © 2015 Elsevier B.V. All rights reserved.

Seasonal variation in plasma catecholamines and adipose tissue lipolysis in adult female green sea turtles (Chelonia mydas).

PubMed

Hamann, Mark; Limpus, Colin J; Whittier, Joan M

2003-02-15

We investigated three aspects of potential interrenal regulation of reproduction in female green sea turtles, Chelonia mydas. First, seasonal trends in plasma catecholamines were examined from female C. mydas at different stages of their reproductive cycles. Second, variation in catecholamine levels during a nesting season were analysed in relation to restraint time, and ecological variables such as nesting habitat, body size, and reproductive investment. Third, catecholamine and corticosterone (CORT) induced lipolysis was investigated with adipose tissue collected from gravid green turtles, using in vitro incubations. Plasma epinephrine (EPI) was lowest in non-vitellogenic (1.55 +/- 0.26 ng/ml) and post-breeding (1.57 +/- 0.22 ng/ml) females, and highest in courting females (2.87 +/- 0.28). Concentrations of norepinephrine (NE) and EPI were relatively constant throughout a nesting season, and not significantly related to restraint time, reproductive investment or nesting habitat. In vitro concentrations of CORT (>3 ng/ml) and NE (2 ng/ml) induced significant release of glycerol after 6h of incubation. Epinephrine tended to induce an antilipolytic affect at low concentrations (0.25 ng/ml) and a net lipolytic response at higher concentrations (>1 ng/ml). Our data suggest that EPI may play a role in regulating body condition during vitellogenesis, and maintaining energy stores during prolonged aphagia during courtship and nesting in female green sea turtles. Furthermore, we provide preliminary evidence that suggests that catecholamine production may be either down regulated or de-sensitised in gravid female C. mydas. Copyright 2003 Elsevier Science (USA)

Personality and innate immune defenses in a wild bird: Evidence for the pace-of-life hypothesis.

PubMed

Jacques-Hamilton, Rowan; Hall, Michelle L; Buttemer, William A; Matson, Kevin D; Gonҫalves da Silva, Anders; Mulder, Raoul A; Peters, Anne

2017-02-01

We tested the two main evolutionary hypotheses for an association between immunity and personality. The risk-of-parasitism hypothesis predicts that more proactive (bold, exploratory, risk-taking) individuals have more vigorous immune defenses because of increased risk of parasite exposure. In contrast, the pace-of-life hypothesis argues that proactive behavioral styles are associated with shorter lifespans and reduced investment in immune function. Mechanistically, associations between immunity and personality can arise because personality differences are often associated with differences in condition and stress responsiveness, both of which are intricately linked with immunity. Here we investigate the association between personality (measured as proactive exploration of a novel environment) and three indices of innate immune function (the non-specific first line of defense against parasites) in wild superb fairy-wrens Malurus cyaneus. We also quantified body condition, hemoparasites (none detected), chronic stress (heterophil:lymphocyte ratio) and circulating corticosterone levels at the end of the behavioral test (CORT, in a subset of birds). We found that fast explorers had lower titers of natural antibodies. This result is consistent with the pace-of-life hypothesis, and with the previously documented higher mortality of fast explorers in this species. There was no interactive effect of exploration score and duration in captivity on immune indices. This suggests that personality-related differences in stress responsiveness did not underlie differences in immunity, even though behavioral style did modulate the effect of captivity on CORT. Taken together these results suggest reduced constitutive investment in innate immune function in more proactive individuals. Copyright © 2016 Elsevier Inc. All rights reserved.

The discontent degree in relations with the proximal social environment and adolescent personality features in Timis County, Romania.

PubMed

Petrescu, Cristina; Vlaicu, Brigitha

2015-01-01

In our study we investigated whether there is a relation between the degree of discontent in relations with the proximal social environment (family and peer groups) and adolescent personality features. The study was conducted on a statistical representative and homogenous sample consisting of 2908 teenagers (51.5% girls and 48.5 % boys, aged between 15 and 19 years). It was an observational (case) study and it consisted in 2 questionnaires applying: Freiburg Personality Inventory (212 items) and CORT 2004 questionnaire (116 items, 6 referring to the discontent levels created by proximal social environment). Cronbach's alpha index was 0.802 for FPI and 0,910 for CORT 2004. Statistical analysis was performed by SPSS 16 program applying Chi square (χ2) and gamma (γ) correlation. Depression and Emotional lability correlated positively and powerfully with q15 (discontent degree of relations with present friend-peers) (γ = 0.471, Sig. 0.000, and γ = 0.383, Sig. 0.000, respectively) and q5 (discontent degree of the relation with parents) (γ = 0.380, Sig. 0.000, and γ = 0.337, Sig. 0.000, respectively). Sociability and calm correlated negative with q5 (γ = -0.14, Sig. 0.000, and γ = -0.35, Sig. 0.000, respectively), q15 (γ = -0.33, Sig. 000 and γ = -0.18, Sig. 000, respectively). In conclusion, there is direct proportional relation between the discontent degree of relations with friend-peers and parents and depression and emotional lability, and inverse proportional relation of friend-peers and parents with sociability and calm.

76 FR 58562 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-21

... RESTAURANTES, S.A. DE C.V., Martin L. Guzman 259-3, Colonia Villa de Cortes, Delegacion Benito Juarez, Mexico...); (ENTITY) [SDNTK]. 3. FLORBEL OPERADORA DE RESTAURANTES, S.A. DE C.V., Mexico City, Distrito Federal...

Effects of reproductive status on behavioral and endocrine responses to acute stress in a biparental rodent, the California mouse (Peromyscus californicus)

PubMed Central

Chauke, Miyetani; Malisch, Jessica L.; Robinson, Cymphonee; de Jong, Trynke R.; Saltzman, Wendy

2014-01-01

In several mammalian species, lactating females show blunted neural, hormonal, and behavioral responses to stressors. It is not known whether new fathers also show stress hyporesponsiveness in species in which males provide infant care. To test this possibility, we determined the effects of male and female reproductive status on stress responsiveness in the biparental, monogamous California mouse (Peromyscus californicus).Breeding (N=8 females, 8 males), nonbreeding (N=10 females, 10 males) and virgin mice (N=12 females, 9 males) were exposed to a 5-min predator-urine stressor at two time points, corresponding to the early postpartum (5–7 days postpartum) and mid/late postpartum (19–21 days postpartum) phases, and blood samples were collected immediately afterwards. Baseline blood samples were obtained 2 days prior to each stress test. Baseline plasma corticosterone (CORT) concentrations did not differ among male or female groups. CORT responses to the stressor did not differ among female reproductive groups, and all three groups showed distinct behavioral responses to predator urine. Virgin males tended to increase their CORT response from the first to the second stress test, while breeding and nonbreeding males did not. Moreover, virgin and nonbreeding males showed significant behavioral changes in response to predator urine, whereas breeding males did not. These results suggest that adrenocortical responses to a repeated stressor in male California mice may be modulated by cohabitation with a female, whereas behavioral responses to stress may be blunted by parental status. PMID:21557946

Effects of reproductive status on behavioral and endocrine responses to acute stress in a biparental rodent, the California mouse (Peromyscus californicus).

PubMed

Chauke, Miyetani; Malisch, Jessica L; Robinson, Cymphonee; de Jong, Trynke R; Saltzman, Wendy

2011-06-01

In several mammalian species, lactating females show blunted neural, hormonal, and behavioral responses to stressors. It is not known whether new fathers also show stress hyporesponsiveness in species in which males provide infant care. To test this possibility, we determined the effects of male and female reproductive status on stress responsiveness in the biparental, monogamous California mouse (Peromyscus californicus). Breeding (N=8 females, 8 males), nonbreeding (N=10 females, 10 males) and virgin mice (N=12 females, 9 males) were exposed to a 5-min predator-urine stressor at two time points, corresponding to the early postpartum (5-7 days postpartum) and mid/late postpartum (19-21 days postpartum) phases, and blood samples were collected immediately afterwards. Baseline blood samples were obtained 2 days prior to each stress test. Baseline plasma corticosterone (CORT) concentrations did not differ among male or female groups. CORT responses to the stressor did not differ among female reproductive groups, and all three groups showed distinct behavioral responses to predator urine. Virgin males tended to increase their CORT response from the first to the second stress test, while breeding and nonbreeding males did not. Moreover, virgin and nonbreeding males showed significant behavioral changes in response to predator urine, whereas breeding males did not. These results suggest that adrenocortical responses to a repeated stressor in male California mice may be modulated by cohabitation with a female, whereas behavioral responses to stress may be blunted by parental status. Published by Elsevier Inc.

Effects of perch access on physiological parameters in caged White Leghorn pullets

USDA-ARS?s Scientific Manuscript database

The neuroendocrine system controls animals' adaptability to their environments by releasing psychotropic compounds such as catecholamines [epinephrine (EP), norepinephrine (NE), and dopamine (DA)], corticosterone (CORT), and serotonin (5-HT). Changes of these neuroendocrine compounds have been used ...

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2011-08-01

evaluated alone and in combination (i.e. pyridostigmine bromide (PB), diethyl-m-toluamide (DEET), 5 lipopolysaccharide (LPS), corticosterone (CORT) and...acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These combined

Red-winged blackbirds (Agelaius phoeniceus) with higher baseline glucocorticoids also invest less in incubation and clutch mass.

PubMed

Schoenle, Laura A; Dudek, Alana M; Moore, Ignacio T; Bonier, Frances

2017-04-01

Glucocorticoid hormones facilitate responses to environmental challenges by mediating diverse physiological and behavioral changes, including resource mobilization and altered reproductive effort. Elevated glucocorticoids might indicate that an individual is facing high levels of environmental challenges and thus, elevated concentrations might be associated with reduced fitness (CORT-fitness hypothesis). Alternatively, the energetic demands of reproduction might be a challenge that requires elevated glucocorticoids to mobilize resources to support reproductive effort, ultimately increasing reproductive investment and fitness (CORT-adaptation hypothesis). Investigations of glucocorticoid-fitness relationships have yielded mixed results. Variation in the direction of this relationship could be caused in part by differences in the contexts in which the relationship was assessed. Incorporating context, such as life history stage, could be key to understanding the role of glucocorticoids in influencing fitness outcomes. We investigated the relationship between corticosterone and reproductive effort and success within a single life history stage: incubation of eggs. In an observational study, we measured baseline corticosterone in incubating female red-winged blackbirds (Agelaius phoeniceus), monitored incubation behavior, and determined hatching success for each nest. Incubating birds with higher baseline corticosterone concentrations had more frequent, shorter incubation bouts and spent less time overall incubating their clutches of eggs than birds with lower corticosterone concentrations. Elevated corticosterone was also associated with lower clutch mass, but neither corticosterone nor incubation effort were correlated with hatching success. Although experimental tests are needed to establish causation, these results suggest that during the incubation period, corticosterone might shift resource investment towards self-maintenance, and away from current reproductive effort. Copyright © 2017 Elsevier Inc. All rights reserved.

Cipadesin A, a bioactive ingredient of Xylocarpus granatum, produces antidepressant-like effects in adult mice.

PubMed

Gao, Qiang; Gao, Yuan; Song, Han; Li, Jianli; Wu, Yibing; Shi, Xiaowei; Shi, Haishui; Ma, Yuxia

2016-10-28

Xylocarpus granatum Koenig, widely used in folk medicine in southeast countries, has been reported to exert neuropharmacological activities as well as mood regulation. The neuroprotective activities of limonoids, riches in X. granatum, are poorly understood. To investigate the potential antidepressant-like effects and the underlying mechanisms of cipadesin A, one limonoid component, extracted from X. granatum, in acute stress-induced depression mouse models. Antidepressant-like effects of cipadesin A were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system. Antidepressant-like effects of cipadesin A (5, 15, 50mg/kg/day for 7days, intragastrically) were estimated through forced-swimming test (FST), tail suspension test (TST) and open field test (OFT). Effects of cipadesin A on hypothalamus-pituitary- adrenal (HPA) axis were evaluated by analysis of serum corticosterone (CORT) and adrenocorticotropic hormone (ACTH) using enzyme-linked immunosorbent assay (ELISA). Cipadesin A administration significantly reduced the floating time in the FST and immobility time in the TST (15-50mg/kg). Cipadesin A dose-dependently increased the time in the central zone in the OFT (5-50mg/kg), without altering the locomotor activity. Moreover, repeated cipadesin A treatment significantly inhibited the increase levels of serum CORT (5-50mg/kg), ACTH (15-50mg/kg) following the forced swimming, but not in the absence of stress. Cipadesin A has antidepressant-like activities in acute stressed mice model of depression, which likely occurs by inhibiting the HPA axis activity response to stress. These data support further exploration for developing cipadesin A as a potential agent to treat depression and anxiety disorders. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Chronic intermittent ethanol exposure during adolescence: Effects on stress-induced social alterations and social drinking in adulthood.

PubMed

Varlinskaya, Elena I; Kim, Esther U; Spear, Linda P

2017-01-01

We previously observed lasting and sex-specific detrimental consequences of early adolescent intermittent ethanol exposure (AIE), with male, but not female, rats showing social anxiety-like alterations when tested as adults. The present study used Sprague Dawley rats to assess whether social alterations induced by AIE (3.5g/kg, intragastrically, every other day, between postnatal days [P] 25-45) are further exacerbated by stressors later in life. Another aim was to determine whether AIE alone or in combination with stress influenced intake of a sweetened ethanol solution (Experiment 1) or a sweetened solution ("supersac") alone (Experiment 2) under social circumstances. Animals were exposed to restraint on P66-P70 (90min/day) or left nonstressed, with corticosterone (CORT) levels assessed on day 1 and day 5 in Experiment 2. Social anxiety-like behavior emerged after AIE in non-stressed males, but not females, whereas stress-induced social anxiety was evident only in water-exposed males and females. Adult-typical habituation of the CORT response to repeated restraint was not evident in adult animals after AIE, a lack of habituation reminiscent of that normally evident in adolescents. Neither AIE nor stress affected ethanol intake under social circumstances, although AIE and restraint independently increased adolescent-typical play fighting in males during social drinking. Among males, the combination of AIE and restraint suppressed "supersac" intake; this index of depression-like behavior was not seen in females. The results provide experimental evidence associating adolescent alcohol exposure, later stress, anxiety, and depression, with young adolescent males being particularly vulnerable to long-lasting adverse effects of repeated ethanol. This article is part of a Special Issue entitled SI: Adolescent plasticity. Copyright © 2016 Elsevier B.V. All rights reserved.

Light and water are not simple conditions: fine tuning of animal housing in male C57BL/6 mice.

PubMed

Langgartner, Dominik; Foertsch, Sandra; Füchsl, Andrea M; Reber, Stefan O

2017-01-01

While animal housing conditions are highly controlled and standardized between different laboratories, there are still many subtle differences that unavoidably influence the host organisms and, consequently, interlaboratory reproducibility. Here, we investigated the physiological and immunological consequences between two light/dark cycle (LDC) lengths (14-h/10-h vs. 12-h/12-h LDC) and two commonly used forms of drinking water (acidified drinking water (AW) versus normal tap water (NW)) in single-housed (SH) mice. Our results indicate that SH mice bred under a 12-h/12-h LDC and NW at the supplier's facility showed increased basal morning plasma corticosterone (CORT) levels even 4 weeks after arrival at our animal facility employing a 14-h/10-h LDC and AW. This effect was even more pronounced two weeks after arrival and had abated after 8 weeks. In agreement, increased plasma adrenocorticotropic hormone (ACTH), adrenal in vitro ACTH sensitivity, as well as relative and absolute adrenal weight normalized during this 8-week exposure to the novel and unfamiliar 14-h/10-h LDC and AW. Employment of a 12-h/12-h LDC in our facility completely abrogated the CORT-elevating effects of the 14-h/10-h LDC, despite these animals drinking AW. When both the water and light conditions were matched to those at the supplier's facility, we observed a further reduction in adrenal weight, increased thymus weight, and decreased pro-inflammatory cytokine secretion of isolated and anti-CD3/28-stimulated mesenteric lymph node cells. In summary, our results indicate that prolonged alteration of both the light phase and drinking water represent severe and long-lasting stressors for laboratory rodents. These findings are of general interest for all scientists obtaining their experimental animals from conventional suppliers.

"Effects of the novel relatively short-acting kappa opioid receptor antagonist LY2444296 in behaviors observed after chronic extended-access cocaine self-administration in rats".

PubMed

Valenza, Marta; Butelman, Eduardo R; Kreek, Mary Jeanne

2017-08-01

The recruitment of the stress circuitry contributes to a shift from positive to negative reinforcement mechanisms sustaining long-term cocaine addiction. The kappa opioid receptor (KOPr) signaling is upregulated by stress and chronic cocaine exposure. While KOPr agonists induce anhedonia and dysphoria, KOPr antagonists display antidepressant and anxiolytic properties. Most of the knowledge on KOPr antagonism is based on drugs with unusual pharmacokinetic and pharmacodynamic properties, complicating interpretation of results. Here we characterized in vivo behavioral and neuroendocrine effects of the novel relatively short-acting KOPr antagonist LY2444296. To date, no study has investigated whether systemic KOPr blockade reduced anxiety-like and depressive-like behaviors in animals previously exposed to chronic extended access cocaine self-administration. We tested the effect of LY2444296 in blocking KOPr-mediated aversive and neuroendocrine effects. Then, we tested acute systemic LY2444296 in reducing anxiety- and depression-like behaviors, as well as releasing the stress hormone corticosterone (CORT), observed after chronic extended access (18 h/day for 14 days) cocaine self-administration. LY2444296 blocked U69,593-induced place aversion and -reduced motor activity as well as U69,593-induced release of serum CORT, confirming its major site of action, without exerting an effect per se. Acute systemic administration of LY2444296 reduced anxiety-like and depressive-like behaviors, as well as CORT release, in rats tested after chronic extended access cocaine self-administration, but not in cocaine-naïve rats. Results suggest that acute blockade of KOPr by a relatively short-acting antagonist produces therapeutic-like effects selectively in rats with a history of chronic extended access cocaine self-administration.

Sahagún's "Florentine codex," a little known Aztecan natural history of the Valley of Mexico.

PubMed

Reeves, Henry M

2006-01-01

Franciscan missionary Fray Bernardino de Sahagún arrived in New Spain (Mexico) in 1529 to proselytize Aztecs surviving the Conquest, begun by Hernán Cortés in 1519. About 1558 he commenced his huge opus "Historia general de las cosas de Nueva España" completed in Latin-Nahuatl manuscript in 1569. The best surviving version, the "Florentine Codex," 1579 in Spanish-Nahuatl, is the basis for the editions published since 1829. The first English translation was issued in 13 volumes between 1950 and 1982, and the first facsimile was published in 1979. Book 11, "Earthly things," is a comprehensive natural history of the Valley of Mexico based on pre-Cortésian Aztec knowledge. Sahagún's work, largely unknown among English-speaking biologists, is an untapped treasury of information about Aztecan natural history. It also establishes the Aztecs as the preeminent pioneering naturalists of North American, and Sahagún and his colleagues as their documentarians.

The Hispanicization of the United States.

ERIC Educational Resources Information Center

Nostrand, Richard L.

Two strikingly contrasting culture groups, Latin Americans and Anglo Americans, overlap in a Borderlands that straddles the international boundary between the United States and Mexico. This overlap began with the Aztec conquest by Cortes which triggered the intermixing and miscegenation between Spaniards and Indians that produced a mestizo people…

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)

EPA Science Inventory

While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral fimctions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

Activation of the Hypothalamic-Pituitary-Adrenal (HPA) Axis Following Extended Exposure to Atrazine (ATR)###

EPA Science Inventory

While it is known that adrenal steroids impact reproduction and a variety of other physiological and behavioral functions, disruption of the HPA-axis is not typically considered in toxicological studies. Here we characterize changes in basal corticosterone (CORT) and progesterone...

Conquistadors. Teaching Guide.

ERIC Educational Resources Information Center

Larson, Susan Booth

This teaching guide is comprised of four interdisciplinary units dealing with the expeditions of conquistadors in the New World: (1) "Cortes and the Aztecs: Different Views of the World"; (2) "Pizarro and the Incas: The 'What Ifs?' of History"; (3) "Orellana and the Amazon: Human and Environmental Issues"; and (4)…

Atrazine Does Not Induce Pica Behavior at Doses that Increase Hypothalamic-Pituitary-Adrenal Axis Activation and Cause Conditioned Taste Avoidance.

EPA Science Inventory

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH), serum corticosterone (CORT) and progesterone. The mechanism for these effects is unknown. To tes...

Repeated exposure to two stressors in sequence demonstrates that corticosterone and paraventricular nucleus of the hypothalamus interleukin-1β responses habituate independently.

PubMed

Lovelock, D F; Deak, T

2017-09-01

A wide range of stress-related pathologies such as post-traumatic stress disorder are considered to arise from aberrant or maladaptive forms of stress adaptation. The hypothalamic-pituitary-adrenal (HPA) axis readily adapts to repeated stressor exposure, yet little is known about adaptation in neuroimmune responses to repeated or sequential stress challenges. In Experiment 1, rats were exposed to 10 days of restraint alone (60 minutes daily), forced swim alone (30 minutes daily) or daily sequential exposure to restraint (60 minutes) followed immediately by forced swim (30 minutes), termed sequential stress exposure. Habituation of the corticosterone (CORT) response occurred to restraint by 5 days and swim at 10 days, whereas rats exposed to sequential stress exposure failed to display habituation to the combined challenge. Experiment 2 compared 1 or 5 days of forced swim with sequential stress exposure and examined how each affected expression of several neuroimmune and cellular activation genes in the paraventricular nucleus of the hypothalamus (PVN), prefrontal cortex (PFC) and hippocampus (HPC). Sequential exposure to restraint and swim increased interleukin (IL)-1β in the PVN, an effect that was attenuated after 5 days. Sequential stress exposure also elicited IL-6 and tumour necrosis factor-α responses in the HPC and PFC, respectively, which did not habituate after 5 days. Experiment 3 tested whether prior habituation to restraint (5 days) would alter the IL-1β response evoked by swim exposure imposed immediately after the sixth day of restraint. Surprisingly, a history of repeated exposure to restraint attenuated the PVN IL-1β response after swim in comparison to acutely-exposed subjects despite an equivalent CORT response. Overall, these findings suggest that habituation of neuroimmune responses to stress proceeds: (i) independent of HPA axis habituation; (ii) likely requires more daily sessions of stress to develop; and (iii) IL-1β displays a greater tendency to habituate after repeated stress challenges compared to other stress-reactive cytokines. © 2017 British Society for Neuroendocrinology.

ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE HPA-AXIS ACTIVATION AND CAUSE CONDITIONED TASTE AVERSION.

EPA Science Inventory

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a NOEL equal to 5mg/kg. The mechanism for these effects ...

Metacognition, Motivation, and Emotions: Contribution of Self-Regulated Learning to Solving Mathematical Problems

ERIC Educational Resources Information Center

Tzohar-Rozen, Meirav; Kramarski, Bracha

2014-01-01

Mathematical problem solving is one of the most valuable aspects of mathematics education. It is also the most difficult for elementary-school students (Verschaffel, Greer, & De Corte, 2000). Students experience cognitive and metacognitive difficulties in this area and develop negative emotions and poor motivation, which hamper their efforts…

78 FR 36635 - Additional Designations, Foreign Narcotics Kingpin Designation Act

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-18

...) (individual) [SDNTK] (Linked To: RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V.). 2. BUENROSTRO VILLA, Denisse... (Mexico) (individual) [SDNTK] (Linked To: RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V.). 8. CORTES...]. 15. RESTAURANT BAR LOS ANDARIEGOS, S.A. DE C.V. (a.k.a. BARBARESCO RESTAURANT), [[Page 36638

Customized On-site Resource Training Services (CORTS): A Partnership Program.

ERIC Educational Resources Information Center

Macquarie Univ., North Ryde (Australia). Special Education Centre.

In 1983, New Brunswick Community College-Moncton (NBCCM) was awarded funding to establish a Computer Aided Drafting/Manufacturing (CAD/CAM) resource center to train students and assist industry in researching and adopting CAD/CAM technology. However, inherent constraints in industry and the absorption of college resources by in-house training…

Concentrating Solar Power Projects - Extresol-2 | Concentrating Solar Power

Science.gov Websites

Sesmero (Badajoz) Owner(s): ACS/Cobra Group (100%) Technology: Parabolic trough Turbine Capacity: Net : 158,000 MWh/yr (Expected/Planned) Contact(s): Manuel Cortes; Ana Salazar Company: ACS/Cobra Group Break Project Type: Commercial Participants Developer(s): ACS/Cobra Group Owner(s) (%): ACS/Cobra Group (100

Concentrating Solar Power Projects - Extresol-3 | Concentrating Solar Power

Science.gov Websites

Sesmero (Badajoz) Owner(s): ACS/Cobra Group (100%) Technology: Parabolic trough Turbine Capacity: Net : 158,000 MWh/yr (Expected/Planned) Contact(s): Manuel Cortes; Ana Salazar Company: ACS/Cobra Group Break years Project Type: Commercial Participants Developer(s): ACS/Cobra Group Owner(s) (%): ACS/Cobra Group

To designate the facility of the United States Postal Service located at 1449 West Avenue in Bronx, New York, as the "Private Isaac T. Cortes Post Office".

THOMAS, 111th Congress

Rep. Crowley, Joseph [D-NY-7

2010-09-23

Senate - 12/22/2010 Read twice and referred to the Committee on Homeland Security and Governmental Affairs. (All Actions) Tracker: This bill has the status Passed HouseHere are the steps for Status of Legislation:

Ets-1 is a target of MAPK signaling in the embryonic anterior pituitary gland during glucocorticoid initiation of pituitary growth hormone expression

USDA-ARS?s Scientific Manuscript database

Glucocorticoids play a critical role in functional differentiation of somatotrophs, the growth hormone (GH)-producing cells within the anterior pituitary gland. In chicken embryonic day 11 (e11) pituitary cells, premature induction of growth hormone (GH) resulting from corticosterone (CORT) treatmen...

The Mexican American Heritage: With Writing Exercises.

ERIC Educational Resources Information Center

Jimenez, Carlos M.

Written by a Los Angeles history teacher frustrated by the lack of culturally relevant materials, this book covers some of the most interesting events in the history of Mexico and the heritage of Mexican Americans. Chapters are: (1) Indian Mexico (Teotihuacan, the Maya, the Toltecs, and the Aztecs); (2) La Conquista (Cortes and Moctezuma, conquest…

Appraising Lexical Bundles in Mathematics Classroom Discourse: Obligation and Choice

ERIC Educational Resources Information Center

Herbel-Eisenmann, Beth; Wagner, David

2010-01-01

Working from a large corpus of transcripts from secondary mathematics classrooms, we identify patterns of speech that encode interpersonal positioning. We extend our analysis from a previous article (Herbel-Eisenmann, Wagner & Cortes, Educ Stud Math, 2010, in press), in which we introduced a concept from corpus linguistics--a "lexical bundle,"…

High-field specific heats of A15 V3Si and Nb3Sn

NASA Astrophysics Data System (ADS)

Stewart, G. R.; Brandt, B. L.

1984-04-01

In order to further understand the anomalous behavior of the specific heat of Nb3Sn in an 18-T magnetic field discovered by Stewart, Cort, and Webb

Longitudinal changes in serum catecholamines, dopamine, serotonin, ACTH and cortisol in pregnant Spanish mares.

PubMed

Marcilla, María; Muñoz, Ana; Satué, Katy

2017-12-01

Systemic physiological changes required for placental and fetal development during pregnancy are associated with an activation of the sympathetic nervous system (SNS) and the hypothalamus-pituitary-adrenal axis (HPA) in women, but this fact has not been investigated in mares. Venous blood samples were taken monthly from 31 successful Spanish mares during the 11months of pregnancy. During the first 4months of pregnancy, adrenaline (AD), dopamine (DOPA) and ACTH increases, whereas 5-hydroxitryptamine (5-HT) decreased, and noradrenaline (NAD) and cortisol (CORT) did not change. Serum NAD increased at 8th month, 5-HT at 5th, 7th months, and DOPA increased progressively between the 5th and 8th months and CORT concentrations peak at 5th month. During the three last months of pregnancy, NAD, 5-TH and DOPA decreased, particularly at the 11th month. These results confirmed an activation of the SNS and the HPA axis in pregnant mares during successful pregnancies. The next step would be to elucidate whether these changes also appear in unsuccessful pregnancies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Characterization of Mesocarp and Kernel Lipids from Elaeis guineensis Jacq., Elaeis oleifera [Kunth] Cortés, and Their Interspecific Hybrids.

PubMed

Lieb, Veronika M; Kerfers, Margarete R; Kronmüller, Amrei; Esquivel, Patricia; Alvarado, Amancio; Jiménez, Víctor M; Schmarr, Hans-Georg; Carle, Reinhold; Schweiggert, Ralf M; Steingass, Christof B

2017-05-10

Morphological traits, total lipid contents, and fatty acid profiles were assessed in fruits of several accessions of Elaeis oleifera [Kunth] Cortés, Elaeis guineensis Jacq., and their interspecific hybrids. The latter featured the highest mesocarp-to-fruit ratios (77.9-78.2%). The total lipid contents of both E. guineensis mesocarp and kernel were significantly higher than for E. oleifera accessions. Main fatty acids comprised C16:0, C18:1n9, and C18:2n6 in mesocarp and C12:0, C14:0, and C18:1n9 in kernels. E. oleifera samples were characterized by higher proportions of unsaturated long-chain fatty acids. Saturated medium-chain fatty acids supported the clustering of E. guineensis kernels in multivariate statistics. Hybrid mesocarp lipids had an intermediate fatty acid composition, whereas their kernel lipids resembled those of E. oleifera genotypes. Principal component analysis based on lipid contents and proportions of individual fatty acids permitted clear-cut distinction of E. oleifera, E. guineensis, and their hybrids.

Glucocorticoids and 11β-HSD1 are major regulators of intramyocellular protein metabolism

PubMed Central

Hassan-Smith, Zaki K; Doig, Craig L; Sherlock, Mark; Stewart, Paul M; Lavery, Gareth G

2016-01-01

The adverse metabolic effects of prescribed and endogenous glucocorticoid excess, ‘Cushing’s syndrome’, create a significant health burden. While skeletal muscle atrophy and resultant myopathy is a clinical feature, the molecular mechanisms underpinning these changes are not fully defined. We have characterized the impact of glucocorticoids upon key metabolic pathways and processes regulating muscle size and mass including: protein synthesis, protein degradation, and myoblast proliferation in both murine C2C12 and human primary myotube cultures. Furthermore, we have investigated the role of pre-receptor modulation of glucocorticoid availability by 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in these processes. Corticosterone (CORT) decreased myotube area, decreased protein synthesis, and increased protein degradation in murine myotubes. This was supported by decreased mRNA expression of insulin-like growth factor (IGF1), decreased activating phosphorylation of mammalian target of rapamycin (mTOR), decreased phosphorylation of 4E binding protein 1 (4E-BP1), and increased mRNA expression of key atrophy markers including: atrogin-1, forkhead box O3a (FOXO3a), myostatin (MSTN), and muscle-ring finger protein-1 (MuRF1). These findings were endorsed in human primary myotubes, where cortisol also decreased protein synthesis and increased protein degradation. The effects of 11-dehydrocorticosterone (11DHC) (in murine myotubes) and cortisone (in human myotubes) on protein metabolism were indistinguishable from that of CORT/cortisol treatments. Selective 11β-HSD1 inhibition blocked the decrease in protein synthesis, increase in protein degradation, and reduction in myotube area induced by 11DHC/cortisone. Furthermore, CORT/cortisol, but not 11DHC/cortisone, decreased murine and human myoblast proliferative capacity. Glucocorticoids are potent regulators of skeletal muscle protein homeostasis and myoblast proliferation. Our data underscores the potential use of selective 11β-HSD1 inhibitors to ameliorate muscle-wasting effects associated with glucocorticoid excess. PMID:27048233

Prenatal ethanol exposure programs an increased susceptibility of non-alcoholic fatty liver disease in female adult offspring rats

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shen, Lang; Liu, Zhongfen; Gong, Jun

Prenatal ethanol exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and adult offspring. However, whether PEE increases the susceptibility to non-alcoholic fatty liver disease (NAFLD) in offspring and its underlying mechanism remain unknown. This study aimed to demonstrate an increased susceptibility to high-fat diet (HFD)-induced NAFLD and its intrauterine programming mechanisms in female rat offspring with PEE. Rat model of intrauterine growth retardation (IUGR) was established by PEE, the female fetus and adult offspring that fed normal diet (ND) or HFD were sacrificed. The results showed that, in PEE + ND group, serum corticosterone (CORT) slightly decreased and insulin-like growthmore » factor-1 (IGF-1) and glucose increased with partial catch-up growth; In PEE + HFD group, serum CORT decreased, while serum IGF-1, glucose and triglyceride (TG) increased, with notable catch-up growth, higher metabolic status and NAFLD formation. Enhanced liver expression of the IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced expression of lipid output were accompanied in PEE + HFD group. In PEE fetus, serum CORT increased while IGF-1 decreased, with low body weight, hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1 expression as well as lipid output was down-regulated, while lipid synthesis significantly increased. Based on these findings, we propose a “two-programming” hypothesis for an increased susceptibility to HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine programming of liver glucose and lipid metabolic function is “the first programming”, and postnatal adaptive catch-up growth triggered by intrauterine programming of GC-IGF1 axis acts as “the second programming”. - Highlights: • Prenatal ethanol exposure increase the susceptibility of NAFLD in female offspring. • Prenatal ethanol exposure reprograms fetal liver’s glucose and lipid metabolism . • Prenatal ethanol exposure cause the adaptive change of glucocorticoid-IGF1 axis.« less

Effect of acute heat stress on rat adrenal glands: a morphological and stereological study.

PubMed

Koko, Vesna; Djordjeviae, Jelena; Cvijiae, Gordana; Davidoviae, Vukosava

2004-11-01

The morphological and stereological structure of rat adrenal gland was analysed by light microscopy after an acute (60 min) exposure to high ambient temperature (38 degrees C). A significant increase in plasma corticotrophin (ACTH) and serum corticosterone (CORT) concentrations was observed, confirming that acute heat exposure has a strong stressful effect. Under these conditions the adrenal gland mass and volume were decreased, probably as the consequence of adrenal cortex reduction, especially that of the zona fasciculata (ZF). Histological examination revealed that many ZF cells were deprived of lipid droplets. Fibrosis was observed in all parts of the adrenal gland, both cortex and medulla, of heat stressed animals. Mitotic figures were absent in cortical cells after heat exposure, but there were no differences in ZF and zona reticularis (ZR) small blood vessels compared to nonstressed controls.

Uninformed in the Information Age: Why Media Necessitate Critical Thinking Education

ERIC Educational Resources Information Center

McBrien, J. Lynn

2005-01-01

Much has been written about the power of media to influence the public through instruments of advertising and a variety of venues (Considine & Haley, 1999; Cortes, 2000; Kilbourne, 1999). In this chapter, the author has chosen to use a singular media focus--news--to support the critical importance of teaching media literacy skills to students. She…

ATRAZINE DOES NOT INDUCE GASTROINTESTINAL DISCOMFORT (PICA) IN RATS AT DOSES THAT INCREASE ACTH ANDCORTICOSTERONE RELEASE AND CAUSE CONDITIONED TASTE AVERSION.

EPA Science Inventory

Previous work has shown that a single oral administration of atrazine (ATR), a chlorotriazine herbicide, induces dose-dependent increases in plasma adrenocorticotropic hormone (ACTH) and serum corticosterone (CORT), with a LOEL of 12.5mg/kg. The mechanism for these effects is unk...

Rationale and Recommended Practices for Using Homegrown Video to Support School-Wide Positive Behavioral Interventions and Supports

ERIC Educational Resources Information Center

Kennedy, M. J.; Swain-Bradway, J.

2012-01-01

Academic and social behaviors are inextricably linked, and a lack of school-appropriate social behaviors can severely impact students' ability to enjoy academic success (Fleming, Harachi, Cortes, Abbott, & Catalano, 2004; McIntosh, Chard, Boland, & Horner 2006). Scott and Barrett (2004) found that every disciplinary referral "costs" students an…

News Letter: European Geophysical Society

DTIC Science & Technology

1998-03-01

CASADO, J.M.; VADILLO, O.; RODRIGUEZ-PASCUA, M.; CICUENDEZ, J.I.; CASAS, A.; CABANAS, I.; RINCON, P.; CORTES, A.; RAMIREZ , M...hydrau- lic conductivity 139 HS008 WIPFLER, EX.; SANCHEZ-VILA, X.; CARRERA- RAMIREZ , J. MC simulation of transport in 2-D heterogenous...GARZOLI, S.L.; RICHARDSON P.; DUNCOMBE RAE, C; FRATANTONI, D.; GONI, G. Benguela current experiment (Poster + Video) RAMIREZ , J

Lexical Bundle Analysis in Mathematics Classroom Discourse: The Significance of Stance

ERIC Educational Resources Information Center

Herbel-Eisenmann, Beth; Wagner, David; Cortes, Viviana

2010-01-01

In this article, we introduce the lexical bundle, defined by corpus linguists as a group of three or more words that frequently recur together, in a single group, in a particular register (Biber, Johansson, Leech, Conrad, & Finegan, 2006; Cortes, "English for Specific Purposes" 23:397-423, 2004). Attention to lexical bundles helps to explore…

Shipboard Acoustic Current Profiling during the Coastal Ocean Dynamics Experiment,

DTIC Science & Technology

1985-05-01

average profile based on the bottori depth estimated from the ship’s posit ion. in the CODEU region. an efficient computer routine was developed for... forex ~and and( port ward comnport ent s of V. at conistant z ., the depth Iill ships coordi- nlatv (’S(Chap 2). The data cort- from I -mintIe

Activation of ATP-sensitive potassium channel by iptakalim normalizes stress-induced HPA axis disorder and depressive behaviour by alleviating inflammation and oxidative stress in mouse hypothalamus.

PubMed

Zhao, Xiao-Jie; Zhao, Zhan; Yang, Dan-Dan; Cao, Lu-Lu; Zhang, Ling; Ji, Juan; Gu, Jun; Huang, Ji-Ye; Sun, Xiu-Lan

2017-04-01

Stress-induced disturbance of the hypothalamic-pituitary-adrenal (HPA) axis is strongly implicated in incidence of mood disorders. A heightened neuroinflammatory response and oxidative stress play a fundamental role in the dysfunction of the HPA axis. We have previously demonstrated that iptakalim (Ipt), a new ATP-sensitive potassium (K-ATP) channel opener, could prevent oxidative injury and neuroinflammation against multiple stimuli-induced brain injury. The present study was to demonstrate the impacts of Ipt in stress-induced HPA axis disorder and depressive behavior. We employed 2 stress paradigms: 8 weeks of continuous restraint stress (chronic restraint stress, CRS) and 2h of restraint stress (acute restraint stress, ARS), to mimic both chronic stress and severe acute stress. Prolonged (4 weeks) and short-term (a single injection) Ipt treatment was administered 30min before each stress paradigm. We found that HPA axis was altered after stress, with different responses to CRS (lower ACTH and CORT, higher AVP, but normal CRH) and ARS (higher CRH, ACTH and CORT, but normal AVP). Both prolonged and short-term Ipt treatment normalized stress-induced HPA axis disorders and abnormal behaviors in mice. CRS and ARS up-regulated mRNA levels of inflammation-related molecules (TNFα, IL-1β, IL-6 and TLR4) and oxidative stress molecules (gp91phox, iNOS and Nrf2) in the mouse hypothalamus. Double immunofluorescence showed CRS and ARS increased microglia activation (CD11b and TNFα) and oxidative stress in neurons (NeuN and gp91phox), which were alleviated by Ipt. Therefore, the present study reveals that Ipt could prevent against stress-induced HPA axis disorders and depressive behavior by alleviating inflammation and oxidative stress in the hypothalamus. Copyright © 2017 Elsevier Inc. All rights reserved.

Electromagnetic Field Effect or Simply Stress? Effects of UMTS Exposure on Hippocampal Longterm Plasticity in the Context of Procedure Related Hormone Release

PubMed Central

Ladage, Kerstin; Krause-Finkeldey, Dorothee; El Ouardi, Abdessamad; Bitz, Andreas; Streckert, Joachim; Hansen, Volkert; Dermietzel, Rolf

2011-01-01

Harmful effects of electromagnetic fields (EMF) on cognitive and behavioural features of humans and rodents have been controversially discussed and raised persistent concern about adverse effects of EMF on general brain functions. In the present study we applied radio-frequency (RF) signals of the Universal Mobile Telecommunications System (UMTS) to full brain exposed male Wistar rats in order to elaborate putative influences on stress hormone release (corticosteron; CORT and adrenocorticotropic hormone; ACTH) and on hippocampal derived synaptic long-term plasticity (LTP) and depression (LTD) as electrophysiological hallmarks for memory storage and memory consolidation. Exposure was computer controlled providing blind conditions. Nominal brain-averaged specific absorption rates (SAR) as a measure of applied mass-related dissipated RF power were 0, 2, and 10 W/kg over a period of 120 min. Comparison of cage exposed animals revealed, regardless of EMF exposure, significantly increased CORT and ACTH levels which corresponded with generally decreased field potential slopes and amplitudes in hippocampal LTP and LTD. Animals following SAR exposure of 2 W/kg (averaged over the whole brain of 2.3 g tissue mass) did not differ from the sham-exposed group in LTP and LTD experiments. In contrast, a significant reduction in LTP and LTD was observed at the high power rate of SAR (10 W/kg). The results demonstrate that a rate of 2 W/kg displays no adverse impact on LTP and LTD, while 10 W/kg leads to significant effects on the electrophysiological parameters, which can be clearly distinguished from the stress derived background. Our findings suggest that UMTS exposure with SAR in the range of 2 W/kg is not harmful to critical markers for memory storage and memory consolidation, however, an influence of UMTS at high energy absorption rates (10 W/kg) cannot be excluded. PMID:21573218

Mutielemental concentration and physiological responses of Lavandula pedunculata growing in soils developed on different mine wastes.

PubMed

Santos, Erika S; Abreu, Maria Manuela; Saraiva, Jorge A

2016-06-01

This study aimed to: i) evaluate the accumulation and translocation patterns of potentially hazardous elements into the Lavandula pedunculata and their influence in the concentrations of nutrients; and ii) compare some physiological responses associated with oxidative stress (concentration of chlorophylls (Chla, Chlb and total), carotenoids, and total protein) and several components involved in tolerance mechanisms (concentrations of proline and acid-soluble thiols and total/specific activity of catalase (CAT) and superoxide dismutase (SOD)), in plants growing in soils with a multielemental contamination and non-contaminated. Composite samples of soils, developed on mine wastes and/or host rocks, and L. pedunculata (roots and shoots) were collected in São Domingos mine (SE of Portugal) and in a reference area with non-contaminated soils, Corte do Pinto, with the same climatic conditions. São Domingos soils had high total concentrations of several hazardous elements (e.g. As and Pb) but their available fractions were small (mainly <5.8 % of the total). Translocation behaviour of elements was not clear according to the physiological importance of the elements. In general, plant shoots from São Domingos had the highest elements concentrations, but only As, Mn and Zn reached phytotoxic concentrations. Concentration of Chlb in shoots from São Domingos was higher than those from Corte do Pinto. No significant differences were obtained between concentrations of Chla, total protein, proline and acid-soluble thiols in shoots collected in both areas, as well as SOD activity (total and specific) and specific CAT activity. Total CAT activity varied with population being lower in the shoots of the plants from São Domingos, but no correlation was obtained between this enzymatic activity and the concentrations of the studied elements in shoots. Lavandula pedunculata plants are able to survive in soils developed on different mine wastes with multielemental contamination and low fertility showing no symptoms (visible and physiological) of phytotoxicity or deficiency. Copyright © 2016 Elsevier Ltd. All rights reserved.

A new extant species of Electribius Crowson from Honduras (Coleoptera: Elateroidea: Artematopodidae).

PubMed

Gimmel, Matthew L; Bocakova, Milada

2015-03-05

A new extant species of Electribius Crowson, E. llamae sp.n., is described from Cusuco National Park, Cortés Province, Honduras. This new species lacks one of the supposed autapomorphies of the genus; therefore the definition of the genus requires modification. A revised key to the known extant species is presented, and their known distributions are mapped.

Guía del Operador del Molino Preliminar -- 2009

Treesearch

Jan Wiedenbeck; Philip H. Mitchell; Bobby Ammerman; Daniel Saloni

2009-01-01

Los fabricantes de productos de madera requieren de una recuperación eficiente de los productos de la madera para que el negocio se mantenga lucrativo. La habilidad de una compañía para obtener el mayor rendimiento en las operaciones de corte de madera (e.g. Molino preliminar) puede variar de acuerdo a la material prima, productos, equipo de...

Earth observation taken by the Expedition 35 crew

NASA Image and Video Library

2013-04-23

ISS035-E-027431 (23 April 2013) --- This oblique Expedition 35 image from the International Space Station shows parts of Mexico, California and Nevada. The Los Angeles Basin can be easily delineated at left center. If the nomenclature for the body of water in the upper right quadrant of the image were the subject of a trivia question, the answer might be "all the above," as it is recognized by a number of names. They include the Gulf of California, Sea of Cortez, Sea of Cortes, Vermilion Sea as well as its local designations in the Spanish language as Mar de Cortes or Mar Bermejo or Golfo de California. It serves to separate the Baja California Peninsula from the Mexican mainland. It is bordered by the states of Baja California, Baja California Sur, Sonora, and Sinaloa (some of which are out of the frame) with a coastline of approximately 4,000 kilometers (2,500 miles). Rivers which flow into the Gulf of California include the Colorado, Fuerte, Mayo, Sinaloa, Sonora and the Yaqui. The gulf's surface area is about 160,000 square kilometers (62,000 square miles). A mass of clouds sits just off the Pacific coast of Baja California and southern California.

Increasing Adult Hippocampal Neurogenesis is Sufficient to Reduce Anxiety and Depression-Like Behaviors.

PubMed

Hill, Alexis S; Sahay, Amar; Hen, René

2015-09-01

Adult hippocampal neurogenesis is increased by antidepressants, and is required for some of their behavioral effects. However, it remains unclear whether expanding the population of adult-born neurons is sufficient to affect anxiety and depression-related behavior. Here, we use an inducible transgenic mouse model in which the pro-apoptotic gene Bax is deleted from neural stem cells and their progeny in the adult brain, and thereby increases adult neurogenesis. We find no effects on baseline anxiety and depression-related behavior; however, we find that increasing adult neurogenesis is sufficient to reduce anxiety and depression-related behaviors in mice treated chronically with corticosterone (CORT), a mouse model of stress. Thus, neurogenesis differentially affects behavior under baseline conditions and in a model of chronic stress. Moreover, we find no effect of increased adult hippocampal neurogenesis on hypothalamic-pituitary-adrenal (HPA) axis regulation, either at baseline or following chronic CORT administration, suggesting that increasing adult hippocampal neurogenesis can affect anxiety and depression-related behavior through a mechanism independent of the HPA axis. The use of future techniques to specifically inhibit BAX in the hippocampus could be used to augment adult neurogenesis, and may therefore represent a novel strategy to promote antidepressant-like behavioral effects.

Cryptic vicariance in the historical assembly of a Baja California peninsular desert biota.

PubMed

Riddle, B R; Hafner, D J; Alexander, L F; Jaeger, J R

2000-12-19

We use analyses of phylogeographic population structure across a suite of 12 mammalian, avian, amphibian, and reptilian species and species-groups to assess the role of Late Miocene to Pleistocene geological history in the evolution of a distinct Baja California Peninsular Desert biota. Comparative examination of phylogroup distributions provides support for previously hypothesized vicariant events produced by: a middle Pleistocene midpeninsular seaway, a late Pliocene northward transgression of the Sea of Cortéz, and a Pliocene seaway across the southern peninsular Isthmus of La Paz. Most of this phylogeographic architecture is cryptically embedded within widespread taxonomic species and species-groups, such that the unique evolutionary history of the Peninsular Desert has been obscured and ignored. The Peninsular Desert can no longer be considered a subset of the Sonoran Desert-it is a separate regional desert with its own unique evolutionary history, ecological arena, and conservation value.

Antidepressant-like effect of the water extract of the fixed combination of Gardenia jasminoides, Citrus aurantium and Magnolia officinalis in a rat model of chronic unpredictable mild stress.

PubMed

Xing, Hang; Zhang, Kuo; Zhang, Ruowen; Shi, Huiyan; Bi, Kaishun; Chen, Xiaohui

2015-12-01

Water extract of the fixed combination of Gardenia jasminoides Ellis fruit, Citrus aurantium L. fruit and Magnolia officinalis Rehd. et Wils. bark, traditional name - Zhi-Zi-Hou-Po (ZZHPD) is used for treatment of depressive-like symptoms in traditional Chinese medicine for centuries. The present study aimed to explore antidepressant-like effects and potential mechanisms of ZZHPD in a rat model of chronic unpredictable mild stress (CUMS). Antidepressant-like effects of ZZHPD were investigated through behavioral tests, and potential mechanism was assessed by neuroendocrine system, neurotrophin and hippocampal neurogenesis. Antidepressant-like effects of ZZHPD (3.66, 7.32 and 14.64 g/kg/day) were estimated through coat state test, sucrose preference test, forced swimming test and open-field test. Effects of ZZHPD on hypothalamic-pituitary-adrenal (HPA) axis were evaluated by hormones measurement and dexamethasone suppression test. In addition, the expression of brain-derived neurotrophic factor (BDNF) in hippocampus was measured, as well as hippocampal neurogenesis was investigated by doublecortin (DCX) and 5-bromo-2-deoxyuridine/neuronal nuclei (BrdU/NeuN). The results demonstrated that ZZHPD significantly reversed the depressive-like behaviors, normalized the levels of adrenocorticotropic hormone (ACTH) and corticosterone (CORT), restored the negative feedback loop of HPA axis and improved the levels of BDNF, DCX and BrdU/NeuN compared with those in CUMS-induced rats. The above results revealed that ZZHPD exerted antidepressant-like effects possibly by normalizing HPA axis function, increasing expression of BDNF in hippocampus and promoting hippocampal neurogenesis. Copyright © 2015 Elsevier GmbH. All rights reserved.

Aspherical dust dynamics code for GIADA experiment in the coma of 67P/Churyumov-Gerasimenko

NASA Astrophysics Data System (ADS)

Ivanovski, Stavro; Zakharov, Vladimir; Della Corte, Vincenzo; Lucarelli, Francesca; Crifo, Jean-Francois; Rotundi, Alessandra; Fulle, Marco

2014-05-01

In 2014, the ESA ROSETTA probe is on its way to face its main scientific objectives by encountering and landing on comet 67P/Churyumov- Gerasimenko. One of the in-situ instrument on board ROSETTA is GIADA (Grain Impact Analyzer and Dust Accumulator)[1], which will measure individual dust grain mass, number density and velocity in the immediate vicinity of the cometary nucleus. Based on the state-of-the-art 3D+t dust coma model [3,4] we developed a 3D+t aspherical dust dynamical code Giaspheria (GIADA aspherical dust analyzer) which treats aspherical dust motion to support the scientific objectives of GIADA. We report the latest improvements in Giaspheria[5,6,7] and the distinctions in the dust dynamics of spherical and aspherical grains using gas solutions for a spherical nucleus not yet data-calibrated. We consider motion of homogeneous, isothermal polygonal convex bodies (close to ellipsoid of revolution with different aspect ratios of axes), moving under influence of three forces: aerodynamic , gravitational and torque. We use the gas distribution (density, velocity, temperature) for a spherical nucleus discussed in [4,8]. We estimate the aerodynamic force from expressions for free molecular interactions and postulate the distribution function of ejection velocity and the distribution function of initial orientation on the surface of the nucleus. We show the dust distribution of aspherical grains at three different heliocentric distances (3AU, 2AU and 1.3 AU) by means of GIPSI simulated GIADA measurements during these stages of the mission. As an input for GIPSI simulations we use the dust and velocity distributions prevised by Giaspheria computations. Acknowledgements: This research has been supported by the Italian Space Agency (ASI) (Ref: n. I/032/05/0) [1] Della Corte V. et al, (2014), Journal of Astronomical Instrumentation (in press). [2] Colangeli, L., et al., Space Science Reviews, Volume 128, Numbers 1-4, 803-821, 2007 [3] Zakharov, V.V., Rodionov A.V., Crifo J.-F., Fulle M., EPSC-DPS , p. 126, 2011 [4] Crifo, J.-F., Loukianov, G.A., Rodionov, A. V., and Zakharov, V. V., Icarus 176, pp. 192-219, 2005 [5] Ivanovski, S. L., Zakharov, V.V., Crifo J.-F., Della Corte V., Rotundi A., EPSC-DPS, p.1371, 2011 [6] Ivanovski, S. L., Zakharov, V.V., Crifo J.-F., Della Corte V., Rotundi A., Vol 7, EPSC2012-592, 2012 [7] Ivanovski, S. L., Zakharov, V.V., Crifo J.-F., Della Corte V., Rotundi A., Vol. 15, EGU2013-11417, 2013 [8] Crifo, J-F., Lukianov,G.A., Rodionov,A.V., Khanlarov,G.O. ,Zakharov,V.V. Icarus Vol.156, 249-268, 2002 [9] Zakharov,V.V., Rodionov, A. V., Lukianov,G.A., Crifo, J-F.,Icarus Vol. 201, I1, p.358-380, 2009

Personnel Selection and White Collar Criminality

DTIC Science & Technology

1993-08-01

Cortes & I Gatti, 1972; Yochelson & Samenow, 1977; Wilson & Herrnstein, 1985; Hirschi & Gottfredson , 1987; Blumstein & Cohen, 1987; Fishbein, 1990; Rowe...offense, and I the environment in which the offense occurs. Sociologists Hirschi and Gottfredson (1988) point out that this tradition has led to the...San Francisco, CA, May, 1993. Hirschi, T., & Gottfredson , M. (1987). Causes of white collar crime. Crin21.qy, 2&, 949-974. I * 46 Hirschi, T

Loss of Talent? Citizenship and Higher Education Access for Undocumented Students. The Claremont Letter. Volume 4, Issue 1

ERIC Educational Resources Information Center

Perez, William

2009-01-01

The author began studying undocumented students in the spring of 2006 to better understand the educational experiences of those who wanted to go to college or who were already in college. He invited three of his CGU (Claremont Graduate University) students--Richard Cortes, Heidi Coronado, and Karina Ramos--to join his research team. To better…

The de Bono LAMS Sequence Series: Template Designs as Knowledge-Mobilising Strategy for 21st Century Higher Education

ERIC Educational Resources Information Center

Dobozy, Eva

2012-01-01

In this paper, the five interlocking de Bono LAMS sequences are introduced as a new form of generic template designs. This transdisciplinary knowledge-mobilising strategy is based on Edward de Bono's attention-directing ideas and thinking skills, commonly known as the CoRT tools. The development of the de Bono LAMS sequence series is an important…

[Chronologic list of the members of the Medical School of the University of Chile (1843-1865)].

PubMed

Costa-Casaretto, C

1992-06-01

The Faculty of Medicine at the University of Chile was started in 1843. Founding professors included Tomas Armstrong, Guillermo C. Blest, Nataniel Cox, Francisco Javier Tocomal, Juan Blest, Julio Lafargue, Manuel Cortés, Luis Ballester. Further nominations, up to a number of 30, took place from 1843 to 1865, and are listed in this paper.

An Investigation of Language Teachers' Explorations of the Use of Corpus Tools in the English for Academic Purposes (EAP) Class

ERIC Educational Resources Information Center

Bunting, John David

2013-01-01

Despite claims that the use of corpus tools can have a major impact in language classrooms (e.g., Conrad, 2000, 2004; Davies, 2004; O'Keefe, McCarthy, & Carter, 2007; Sinclair, 2004b; Tsui, 2004), many language teachers express apparent apathy or even resistance towards adding corpus tools to their repertoire (Cortes, 2013b). This study…

Effects of chronic and repeated repeated coritcosterone administration in rearing chickens on physiology, the onset of lay and egg production in hens.

USDA-ARS?s Scientific Manuscript database

A corticosterone (CORT) model was used to study the effects of repeated stress during rearing phase on physiology and performance of hens’ in subsequent laying period. Two hundred and seventy Hy-line laying birds were reared in environmentally controlled battery cages. At 7, 11, and 15 wk of age bir...

Color temperature of light-emitting diode lighting matters for optimum growth and welfare of broiler chickens.

PubMed

Archer, G S

2018-05-01

Light-emitting diode (LED) light bulbs are becoming more prevalent in broiler production as they are dimmable and more energy efficient than compact fluorescent lamps. Although there is some research on how spectrum of light can affect production, little has been conducted on how it may affect stress, and behavior. To determine how different spectrum of light produced by LED lights could affect production, stress and behavior we raised broilers under either 2700 K (WARM) or 5000 K (COOL) color temperature LED bulbs. To determine stress susceptibility bilateral asymmetry (ASYM, n=128), plasma corticosterone concentrations (CORT, n=40) and heterophil/lymphocyte ratios (HL, n=80) were measured. Fear was measured using tonic immobility (TI, n=128), inversion (INV, n=128) and isolation (ISO, n=128). Weight gain and feed conversion ratio (FCR) were also determined. The COOL birds had lower ASYM (1.65±0.08 mm, P=0.001), CORT (5.8±1.2 ng/dl, P=0.01) and HL (0.16±0.01, P=0.03) than the WARM birds (2.38±0.14 mm, 13.4±2.7 ng/dl and 0.21±0.02, respectively). The COOL birds righted faster during TI (136.2±11.1 s, P=0.001), flapped less intensely during INV (4.1±0.1 flaps/s, P<0.001) and vocalized less during ISO (45.3±2.8 vocalizations, P=0.005) when compared with WARM birds (207.2±15.8 s, 4.9±0.1 flaps/s and 56.5±2.9 vocalizations). The COOL birds (2.89±0.03 kg, P=0.02) grew to a heavier weight at the end of 42 day then WARM birds (2.79±0.03 kg). The COOL birds (1.54±0.03) had better FCR (P=0.02) than WARM birds (1.61±0.01). These results demonstrate that raising broilers under 5000 K LED lights can reduce their stress, fear and increase weight gain when compared with 2700 K. These results indicate that the spectrum of light used for rearing of broilers is not only important for production, but also for welfare of the birds.

Behavioral and endocrine changes following antisense oligonucleotide-induced reduction in the rat NOP receptor.

PubMed

Blakley, Gregory G; Pohorecky, Larissa A; Benjamin, Daniel

2004-02-01

Compared with the use of classic receptor ligands, antisense oligonucleotides (ASO) targeted at specific central nervous system receptors are an effective alternative in experiments designed to examine the behavioral role of such systems. The nociception/orphaninFQ (N/OFQ) system has been implicated in mediating endocrine function, feeding, stress, pain, anxiety, and the rewarding effects of drugs of abuse. The objective of the current study was to examine whether long-term ASO-induced downregulation of N/OFQ's receptor (NOP) produced changes in endocrine, anxiety, nociception and ethanol's (EtOH's) locomotor activating properties. Male Long Evans rats were implanted with osmotic mini-pumps containing ASO for the NOP receptor. ASO was chronically infused for 26 days and, during this time, multiple behavioral and physiological measurements were conducted. ASO infusion significantly reduced expression of the NOP receptor in brain, confirmed by significant reductions of OFQ-stimulated [(35)S]-GTPgammaS binding in the paraventricular nucleus, prefrontal cortex, and septum. Behavioral changes were observed in ASO-treated animals including higher body temperature, increased water intake, decreased corticosterone (CORT) levels, decreased grooming in the open field, increased tail-flick latency, shorter durations on the open arms of the elevated plus maze, and heightened locomotor activity following EtOH. These behavioral, physiological and endocrine changes are relatively consistent with previous findings with agonists and antagonists for the NOP receptor and, taken together, suggest that ASO-induced downregulation of the NOP receptor is an effective method for studying the N/OFQ system.

A Three-Dimensional Foil Bearing Performance Map Applied to Oil-Free Turbomachinery

DTIC Science & Technology

2009-04-01

in diesel engine turbochargers , auxiliary power units (APUs), and selected hot section bearings in gas turbines (7–9). While these Oil-Free...film. Regardless of the strategy, research suggests proper thermal management is a key fundamental necessity for the successful deployment and...Turbo Expo 2006, Barcelona, Spain, GT2006-90572, 2006. 7. Heshmat, H.; Walton, II, J. F.; DellaCorte, C.; Valco, M. Oil-Free Turbocharger

An Analysis of Full Scale Measurements on M/V Stewart J. Cort during the 1979 and 1980 Trial Programs. Parts I and II.

DTIC Science & Technology

1982-02-01

IKCuNITY CLASSIFICATION OF Tm4iS IMAGE (Vrhn Dot& Entered) .,.-’- . . . . . ... .. ... " . . ...... ....... .. . . . . . . . . TABLE OF CONTENTS...11-19 APPENDIX D: BASIC PROCESSING ............................... 11-21 APPENDIX E: SIMULATION OF DATA...equipment previously developed, and an on-board data processing system. These full scale ship trials were the first in history with the objective of directly

Effects of Estradiol on Post-Traumatic Stress Disorder Symptoms

DTIC Science & Technology

2010-03-01

Steroid Metabolism pathways 34 Figure 6. HPG Axis 35 Chapter 3 Figure 1. Effect of 7, 14, and 22 Days of...87 Treatment on Plasma CORT in OVX Sprague-Dawley Rats that were also Immobilization Stressed for 22 -days Figure 3. Effect of Early...for 22 -days Figure 5. Effect of Estradiol, Selective ERα Agonist, and ERβ Agonist 90 Treatment on Pre-Pulse Inhibition in OVX Sprague-Dawley

Keeping "La Llorona" Alive in the Shadow of Cortes: What an Examination of Literacy in Two Mexican Schools Can Teach U.S. Educators

ERIC Educational Resources Information Center

Hall, Anne-Marie

2006-01-01

This article, a 5-month ethnographic research in Oaxaca, Mexico, examines various aspects of the literacy curriculum in 2 Mexican primary schools. The author observed and interviewed 35 students in 6th grade and 7 teachers in 2 schools, as well as examined student writing and teaching materials. The research suggests that though the…

Stress and translocation: alterations in the stress physiology of translocated birds

PubMed Central

Dickens, Molly J.; Delehanty, David J.; Romero, L. Michael

2009-01-01

Translocation and reintroduction have become major conservation actions in attempts to create self-sustaining wild populations of threatened species. However, avian translocations have a high failure rate and causes for failure are poorly understood. While ‘stress’ is often cited as an important factor in translocation failure, empirical evidence of physiological stress is lacking. Here we show that experimental translocation leads to changes in the physiological stress response in chukar partridge, Alectoris chukar. We found that capture alone significantly decreased the acute glucocorticoid (corticosterone, CORT) response, but adding exposure to captivity and transport further altered the stress response axis (the hypothalamic–pituitary–adrenal axis) as evident from a decreased sensitivity of the negative feedback system. Animals that were exposed to the entire translocation procedure, in addition to the reduced acute stress response and disrupted negative feedback, had significantly lower baseline CORT concentrations and significantly reduced body weight. These data indicate that translocation alters stress physiology and that chronic stress is potentially a major factor in translocation failure. Under current practices, the restoration of threatened species through translocation may unwittingly depend on the success of chronically stressed individuals. This conclusion emphasizes the need for understanding and alleviating translocation-induced chronic stress in order to use most effectively this important conservation tool. PMID:19324794

Role of Hypothalamic-Pituitary-Adrenal axis and corticotropin-releasing factor stress system on cue-induced relapse to alcohol seeking.

PubMed

Galesi, Fernanda L; Ayanwuyi, Lydia O; Mijares, Miriam Garcia; Cippitelli, Andrea; Cannella, Nazzareno; Ciccocioppo, Roberto; Ubaldi, Massimo

2016-10-05

A large body of evidence has shown that the Corticotropin Releasing Factor (CRF) system, which plays a key role in stress modulation, is deeply involved in relapse to alcohol seeking induced by exposure to stressful events such as foot shock or yohimbine injections. Exposure to environmental cues is also known to be a trigger for alcohol relapse, nevertheless, the relationship between the relapse evoked by the cue-induced model and the CRF stress systems remains unclear. The purpose of this study was to evaluate, in male Wistar rats, the involvement of the CRF system and Hypothalamic-Pituitary-Adrenal (HPA) axis in relapse induced by environmental cues. Antalarmin, a selective CRF1 receptor antagonist, Metyrapone, a corticosterone (CORT) synthesis inhibitor and CORT were evaluated for their effects on the reinstatement test in a cue-induced relapse model. Antalarmin (20mg/kg) blocked relapse to alcohol seeking induced by environmental cues. Metyrapone (50 and 100mg/kg) also blocked relapse in Wistar rats but only at the highest dose (100mg/kg). Corticosterone had no effect on relapse at the doses tested. The results obtained from this study suggest that the CRF stress system and the HPA axis are involved in cue-induced alcohol relapse. Copyright © 2016 Elsevier B.V. All rights reserved.

Telescopio San Pedro Mártir Observatory preliminary design and project approach

NASA Astrophysics Data System (ADS)

Teran, Jose; Lee, William H.; Richer, Michael G.; Sánchez, Beatriz S.; Urdaibay, David; Hill, Derek; Adriaanse, David; Hernandez-Limonchi, Regina

2016-07-01

The Instituto de Astronomia of the Universidad Nacional Autónoma de México (UNAM) along with Instituto Nacional de Astrofisica, Optica y Electronica, the University of Arizona and the Smithsonian Astrophysical Observatory are developing the Telescopio San Pedro Mártir (TSPM) project, a 6.5m diameter optical telescope. M3 Engineering and Technology Corp. (M3) is the design and construction management firm responsible for all site infrastructure, enclosure and support facilities. The Telescopio San Pedro Mártir project (TSPM) will be located within the San Pedro Mártir National Park in Baja California, Mexico at 2,830 m. above sea level, approximately 65 km. east of the Pacific Ocean, 55km west of the Sea of Cortes (Gulf of California) and 180km south of the United States and México border. The aim of the paper is to present the preliminary design of the site infrastructure, enclosure and support facilities to date and share the design and construction approach.

Effect of simulated transport stress on the rat small intestine: A morphological and gene expression study.

PubMed

Wan, Changrong; Yin, Peng; Xu, Xiaolong; Liu, Mingjiang; He, Shasha; Song, Shixiu; Liu, Fenghua; Xu, Jianqin

2014-04-01

The present study investigated the effects of simulated transport stress on morphology and gene expression in the small intestine of laboratory rats. Sprague Dawley rats were subjected to 35°C and 0.1×g on a constant temperature shaker for physiological, biochemical, morphological and microarray analysis before and after treatment. The treatment induced obvious stress responses with significant decreases in body weight (P<0.01), increases in rectal temperature, serum corticosterone (CORT), serum glucose (GLU), creatine kinase (CK) and lactate dehydrogenase (LDH) levels (P<0.01), as well as expression of Hsp27/70/90 mRNA (P<0.05; P<0.01). The rat jejunum was severely damaged and apoptotic after mimicking transport stress, which may mainly be related to cell death, oxidation reduction and hormone imbalance determined by microarray analysis. The bioinformatics analysis from the present study would provide insight into the potential mechanisms underlying transport stress-induced injury in the rat small intestine. Copyright © 2014 Elsevier Ltd. All rights reserved.

Long-lasting changes in stress-induced corticosterone response and anxiety-like behaviors as a consequence of neonatal maternal separation in Long-Evans rats.

PubMed

Kalinichev, Mikhail; Easterling, Keith W; Plotsky, Paul M; Holtzman, Stephen G

2002-08-01

Early neonatal environmental factors appear to have powerful and long-lasting influences on an organism's physiology and behavior. Long-Evans male rats separated from their dam for 3 h daily over the first 2 weeks of life (maternally separated, MS rats) when tested as adults exhibit exaggerated behavioral and neuroendocrine responses to stress compared to 15-min separated (handled, H) animals. The purpose of this study was to compare male and female adult rats that were MS, H or were undisturbed (nonhandled, NH) as neonates in anxiety-like behaviors, in the elevated plus-maze, and in response to startle-inducing auditory stimuli. We confirmed that MS males oversecrete corticosterone (CORT; 2.5-5 times) in response to mild handling stress. MS males and females were less likely to explore open arms of the plus-maze. MS males exhibited 35% higher startle amplitudes compared to controls. Furthermore, MS males were more likely to emit ultrasonic vocalizations in response to startle than were H controls. However, MS and control females did not differ in auditory startle response or in startle-induced ultrasonic vocalizations. Therefore, experiencing maternal separation results in a long-lasting increase in anxiety-like behaviors that occurs in a sex-dependent manner.

Onset, Timing, and Exposure Therapy of Stress Disorders: Mechanistic Insight from a Mathematical Model of Oscillating Neuroendocrine Dynamics (Open Access)

DTIC Science & Technology

2016-03-25

peptide hormones such as corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH) by circulating glucocorticoids such as cortisol (CORT...As for many other hormones such as gonadotropin- releasing hormone (GnRH), insulin, and growth hormone (GH), the ultradian release pattern of...therapy; GH: growth hormone ; GnRH: gonadotropin-releasing hormone ; GR: glucocorticoid receptors; MDD: major depressive disorder; hnRNA: heterogeneous

Bibliography on Future Trends in Terrorism

DTIC Science & Technology

1998-09-01

Bernhard Restel, et alia. "La police en interfaces: Colloque universitaire de l’Institut Suisse de Police," Revue Internationale de Criminologie et...Convenzione di Ginevra per l’Istituzione di una Corte Penale Internazionale sul Terrorismo : Un document da tornare a leggere," Il Politico, [Rome], 62...The author, who is president of Peru , points out that terrorist organizations in Peru have struggled for a decade to erode the democratic system and

The Centurions vs. the Hydra: French Counterinsurgency in the Peninsular War (1808-1812)

DTIC Science & Technology

2011-06-10

their operational dilemma in different manners. But the analysis also outlined a common denominator to their practices. Leverage of religion , build up...But the analysis also outlined a common denominator to their practices. Leverage of religion , build up of native security forces, and development...armada en los origenese de la Espana liberal, 1808-1823 [Cortes and Military Forces at the Origin of Liberal Spain] (Madrid, Spain: Siglo veintiuno

Neuroimmune Interactions, Low-Dose Sarin Inhalation, and Gulf War Syndrome

DTIC Science & Technology

2012-10-01

antibody-forming cell qPCR real-time PCR CORT corticosterone Introduction Cigarette smoking is a major health risk factor and contributes to over...and PTK activities in splenic T cells One of the earliest effects of TCR ligation is the activation of PTK, including Src-like kinases Fyn and Lck...development of Clara and goblet cells without causing significant lung inflammation, and the SS-induced effects on alveolar architecture are

Conference on the Neurobiology of Learning and Memory (3rd)

DTIC Science & Technology

1988-09-23

TREATMENT IN PARADOXICAL SLEEP I. Portell-Cortes, DEPRIVATION PLATFORMS IN RATS . Norpdo-Bernal Area do Psicobiologia Dept. de Psicologia do la Salut Univ...of California Irvine, CA 92717 Irvine, CA 92717 Dr. Robert W. Doty Dr. David Easton Center for Brain Research School of Social Sciences Univ. of...Ignacio Morgado-Bernal Dr. Georges Moroz Area de Psicobiologia CNS Development Psicologia do la Salud CIBA-GEIGY Corp. Univ. Autonoma do Barcelona DEV

Characterization of seasonal reproductive and stress steroid hormones in wild Radiated Tortoises, Astrochelys radiata.

PubMed

Currylow, Andrea F T; Rafeliarisoa, Tsilavo H; Louis, Edward E; Stanford, Craig B; Randrianjafizanaka, Soary T; Chinn, Sarah M; Crocker, Daniel E

2017-11-01

The critically endangered Radiated Tortoise (Astrochelys radiata) is endemic to the southern coastlines of Madagascar. Once common, wild populations of this tortoise have undergone dramatic declines in recent years. Although there have been studies documenting reproductive activities, reproductive physiological parameters are unknown yet may be crucial in the recovery of the species. Over four research seasons in remote field locations native to A. radiata, we surveyed for, radio-tracked, and sampled wild, free ranging tortoises. We sampled and measured stress and reproductive parameters (corticosterone [CORT], testosterone [T], estradiol-17β [E2], and progesterone [P]) in 311 plasma samples from 203 wild A. radiata, capturing their active period. Generally, hormone concentrations were associated with body condition, temperature, and humidity. There was wide variation in CORT that varied monthly and by group. Juvenile tortoises maintained more than twice the mean basal CORT concentrations than either adult sex, with the most dramatic distinctions in the middle of the wet season. For adult sex hormones, the last months of the dry season and into the wet season when ground humidities are low and just begin to rise prior to temperature declines, male T concentrations gradually increased to a peak before returning to near undetectable values into the dry season. We had limited data for T concentrations in females, but found average T concentrations were much lower than in males and positively correlated with larger female home range sizes. For female hormone cycles, E2 also peaked in the early 1/3 of the wet season along with male T, and was followed by an uptick in P which correlates to the putative ovulatory cycle. Females tracked over four years showed variation in patterns of P, indicating that number and frequency of clutches vary. Our results suggest that 1) there is high species plasticity in response to stress; 2) A. radiata reproductive cycling is somewhat dissociated with courtship timing and is instead triggered by environmental cues; and 3) individual female reproductive output is irregular. This study is oone of the first to document and describe multi-year seasonal stress and reproductive hormones in a free-ranging Malagasy chelonian. These data may be used to identify key high-production habitats for conservation, and aide in captive management and reproduction in assurance colonies for species health and survival. Copyright © 2017 Elsevier Inc. All rights reserved.

Understanding Gulf War Illness: An Integrative Modeling Approach

DTIC Science & Technology

2017-10-01

group (Task 2; Subtask1). The latest iteration of this analysis focused on n=11 animals control and n=11 DFP exposed animals without corticosterone... Groups : 1 – Control Group (Male and Female Intact) 2 – GWI Model – Cort+DFP (Male and Female OVX) 3 – Control OVX (Female) 4 – GWI Model + Enbrel...The designed protocol counts with five basic experimental groups : Group 1 (Untreated Control no toxic exposure); Group 2 (Toxic exposed, no

Injection of Nucleate-Boiling Slug Flows into a Heat Exchange Chamber in Microgravity

DTIC Science & Technology

2015-06-01

Casademunt UNIVERSITAT DE BARCELONA CALLE GRAN VIA DE LES CORTS CATALANES 585 BARCELONA 08007 SPAIN EOARD GRANT #FA8655-12-1- 2060 ...slug flows into a heat exchange chamber in microgravity 5a. CONTRACT NUMBER 5b. GRANT NUMBER FA8655-12-1- 2060 5c. PROGRAM ELEMENT NUMBER...Scientific Research (AFOSR) FINAL REPORT EOARD Grant : FA8655-12-1- 2060 PERIOD: 20 March 2012 – 19 March 2015 PROJECT TITLE

Radioimmunoassay of Urinary Free Cortisol.

DTIC Science & Technology

1976-09-28

materials antigenically similar to cortisol from the urine . The second step is the radioimmunoassay using dextran-coated charcoal to separate bound and...recovery averaged 97.7%. One technician can analyze 100 samples per week. INTRODUCTION cently. radioimmunoassay (R1A) (2. 6. 9. 13 , 14, IS , 26. 29...HILDERBRAND cort icos te i’oid excretion to human pci-form- pared jU st prior to rise by evaporat ing thc ance 1 24 L :\\ lthough the specif icity ofdeter

Thermal Properties of Mineralized and Non Mineralized Type I Collagen in Bone

DTIC Science & Technology

2002-04-01

Heredial, E. Villarreal", J. Ocotldn-Flores2, A. L. Gomez-Cortes’, F. J. Aranda-Manteca 5, E. Orozco’ and L. Bucio’. lInstituto de Fisica , UNAM, Ciudad... Investigaciones en Materiales, UNAM, Ciudad Universitaria, Coyoacan. C.P. 04510. Mexico. D.F.41nstituto de Investigaciones Antropologicas, UNAM...Universitaria, Coyoacan. C.P. 01000, Mexico. D.F.2Centro de -instrumentos, UNAM, Ciudad Universitaria, Coyoacan. C.P. 04510. Mexico. D.F.3Instituto de

DOE/KEURP site operator program. Year 3, Second Quarter Report, October 1--December 31, 1993

DOE Office of Scientific and Technical Information (OSTI.GOV)

Not Available

Kansas State University, with funding support from federal, state, public, and private companies, is participating in the Department of Energy`s Electric Vehicle Site Operator Program. Through participation in this program, Kansas State is displaying, testing, and evaluating electric or hybrid vehicle technology. This participation will provide organizations the opportunity to examine the latest EHV prototypes under actual operating conditions. KSU has purchased several electric cars and proposes to purchase additional electric vehicles. KSU has purchased one G-Van built by Conceptor Industries, Toronto, Canada and has procured two (2) Soleq 1993 Ford EVcort station wagons. During calendar year 1994, the Kansas`more » electric vehicle program expects to purchase a minimum of four and a maximum of eleven additional electric vehicles. The G-Van was signed in order for the public to be aware that it was an electric vehicle. Financial participants` names have been stenciled on the back door of the van. The Soleq EvCorts have not been signed. In order to demonstrate the technology as feasible, the EvCorts were deliberately not signed. The goal is to generate a public perception that this vehicle is no different from any similar internal combustion engine vehicle. Magnetic signs have been made for special functions to ensure sponsor support is recognized and acknowledged.« less

The impacts of invaders: basal and acute stress glucocorticoid profiles and immune function in native lizards threatened by invasive ants.

PubMed

Graham, Sean P; Freidenfelds, Nicole A; McCormick, Gail L; Langkilde, Tracy

2012-05-01

As anthropogenic stressors increase exponentially in the coming decades, native vertebrates will likely face increasing threats from these novel challenges. The success or failure of the primary physiological mediator of these stressors--the HPA axis--will likely involve numerous and chaotic outcomes. Among the most challenging of these new threats are invasive species. These have the capacity to simultaneously challenge the HPA axis and the immune system as they are often associated with, or the cause of, emerging infectious diseases, and energetic tradeoffs with the HPA response can have immunosuppressive effects. To determine the effects of invasive species on the vertebrate GC response to a novel stressor, and on immunity, we examined the effects of invasive fire ants on native lizards, comparing lizards from sites with long histories with fire ants to those outside the invasion zone. We demonstrated higher baseline and acute stress (captive restraint) CORT levels in lizards from within fire ant invaded areas; females are more strongly affected than males, suggesting context-specific effects of invasion. We found no effect of fire ant invasion on the immune parameters we measured (complement bacterial lysis and antibody hemagglutination) with the exception of ectoparasite infestation. Mites were far less prevalent on lizards within fire ant invaded sites, suggesting fire ants may actually benefit lizards in this regard. This study suggests that invasive species may impose physiological stress on native vertebrates, but that the consequences of this stress may be complicated and unpredictable. Copyright © 2012 Elsevier Inc. All rights reserved.

Piracetam attenuates binge eating disorder related symptoms in rats.

PubMed

Hussain, Yusuf; Krishnamurthy, Sairam

2018-06-01

Binge eating disorder (BED) is a stress-related disorder characterized by acute episodes of excessive food intake. Piracetam, a nootropic agent has been reported to show several other neuropharmacological properties. The present study, evaluated the pharmacological effect of piracetam (200 mg/kg i.p.) on BED in female rats, induced by free access to palatable cookies for 2 h on alternate days. BED was confirmed by an increase in binge eating behavior and weight gain. BED leads to anxiety, cognitive and memory deficits, as evaluated by EPM (Elevated plus maze), OFT (open field test), and Y-maze tests. Increased levels of plasma corticosterone (CORT), glutamate in nucleus accumbens (NAC), hypothalamus (HYP) and prefrontal cortex (PFC) indicate stress and excitotoxicity. Moreover, it was observed that the levels of dopamine were higher in NAC and PFC, and less in HYP which may be responsible for motivational behavior for palatable feeding and cognitive deficits. More surprisingly, feeding behaviour regulating hormones namelyleptin was increased and ghrelin level was decreased in BED. Further, level of acetylcholine which regulates cognitive behaviour was compromised in BED. Piracetam significantly decreased binge eating behavior and associated body weight and regulated the levels of concerned neurotransmitters in respective regions. However, piracetam did not alter normal feeding behavior in the fast-refed model. Further, piracetam showed brain region-specific decrease in vascular endothelial growth factor expression. Piracetam showed anxiolytic activity and also alleviated cognitive deficit observed in BED. Hence, preclinical evidence indicates the potential use of piracetam for the treatment of BED. Copyright © 2018 Elsevier Inc. All rights reserved.

Neuroinflammatory Pathobiology in Gulf War Illness: Characterization with an Animal Model

DTIC Science & Technology

2013-08-01

GFAP,IL6,CCL2, TNF, L118, Lif, IL10 Hip, Ctx Ctx Ctx CORT=corticosterone;(200mg/L) for days 7-14 P8= pyridostigmine bromide ;P8(2.5 mg/kg/day, s.c...reversible acetylcholinesterase (AChE) inhibitor pyridostigmine bromide (PB), the insect repellent DEET and, potentially, the nerve agent, sarin. These...acetylcholinesterase (AChE) inhibitor, pyridostigmine bromide (PB), the insect repellent, DEET, and, potentially, acutely to the nerve agent sarin. Previously, we

[The death of Moctezuma II].

PubMed

Espinoza, R; González, C

1995-07-01

Moctezuma was the Aztec emperor when Spaniards arrived in Mexico in 1519. After his entrance in Tenochtitlan, Cortés held the emperor hostage, forcing him to govern under conditions in his own palace. The psychic evolution experienced by Moctezuma until his death in 1520 is analyzed based on testimonial reports of Benal Diaz del Castillo and historian contributions. Although there is evidence that Moctezuma was stoned and wounded by an arrow, we propose the hypothesis that the emperor was affected by a Major Depression.

Salient Feature Identification and Analysis using Kernel-Based Classification Techniques for Synthetic Aperture Radar Automatic Target Recognition

DTIC Science & Technology

2014-03-27

and machine learning for a range of research including such topics as medical imaging [10] and handwriting recognition [11]. The type of feature...1989. [11] C. Bahlmann, B. Haasdonk, and H. Burkhardt, “Online handwriting recognition with support vector machines-a kernel approach,” in Eighth...International Workshop on Frontiers in Handwriting Recognition, pp. 49–54, IEEE, 2002. [12] C. Cortes and V. Vapnik, “Support-vector networks,” Machine

Complex Host Genetics Influence the Microbiome in Inflammatory Bowel Disease

DTIC Science & Technology

2016-09-09

specific bacterial taxa. Methods Ethics and consent This study was approved by the Partners Human Re- search Committee, 116 Huntington Avenue, Boston, MA...microbial ecology . Proc Natl Acad Sci U S A 2005, 102:11070–11075. 17. Hashimoto T, Perlot T, Rehman A, Trichereau J, Ishiguro H, Paolino M, Sigl V...JM: ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation. Nature 2012, 487:477–481. 18. Cortes A, Brown MA: Promise and

Temporal planning for transportation planning and scheduling

NASA Technical Reports Server (NTRS)

Frederking, Robert E.; Muscettola, Nicola

1992-01-01

In this paper we describe preliminary work done in the CORTES project, applying the Heuristic Scheduling Testbed System (HSTS) to a transportation planning and scheduling domain. First, we describe in more detail the transportation problems that we are addressing. We then describe the fundamental characteristics of HSTS and we concentrate on the representation of multiple capacity resources. We continue with a more detailed description of the transportation planning problem that we have initially addressed in HSTS and of its solution. Finally we describe future directions for our research.

The Effect of Aberrations and Apodisation on the Performance of Coherent Imaging Systems.

DTIC Science & Technology

1986-02-01

later Jacquinot and Roizen-Dossier 27(1964) described the previotic wrk, Since then, many workers (see for example references 28-31) have - cor.t -: .o...transmission loss . The pacier bv Thompson and KriSl 48 ! resents a comoact overview of th-e sub’er! of apodisation as applied to coherent imaging and beam...system. This difficulty translates into extra weight , size, and , excense in any oractical ootical system 152 77V.-- .- --.--- 153 In the theoretical

Envelope Responses in Single-trial EEG Indicate Attended Speaker in a Cocktail Party

DTIC Science & Technology

2014-06-25

attention at the cued location, which may not produce strong lateralization in alpha power. In fact, a similar cocktail party study found that alpha...enhances selective speech envelope tracking in auditory cortex at a ‘ cocktail party ’ J. Neurosci. 33 1417–26 [9] Cherry E C 1953 Some experiments on the...Envelope responses in single-trial EEG indicate attended speaker in a ‘ cocktail party ’ Cort Horton1, Ramesh Srinivasan1,2 and Michael D’Zmura1

Genetic Structure of Anopheles (Nyssorhynchus) marajoara (Diptera: Culicidae) in Colombia

DTIC Science & Technology

2010-01-01

South America . J Infect Dis 186: 999 – 1006 . 2. Mendoza M , Nicholls R , Olano V , Cortés L , 2000 . Situación de la malaria en ...Colombia . Manual de Manejo integral de la malaria. Instituto Nacional de Salud Ed . Bogotá, Columbia: Instituto Nacional de Salud . 3. Herrera...S , Suárez M , Sánchez G , Quiñones M , Herrera M , 1987 . Uso de la técnica inmunoradiometrica (IRMA) en Anopheles de Colombia para la

Dynamics of neuroendocrine stress response: bistability, timing, and control of hypocortisolism

NASA Astrophysics Data System (ADS)

D'Orsogna, Maria; Chou, Tom; Kim, Lae

The hypothalamic-pituitary-adrenal (HPA) axis is a neuroendocrine system that regulates numerous physiological processes. Disruptions in its activity are correlated with stress-related diseases such as post-traumatic stress disorder (PTSD) and major depressive disorder. We characterize ``normal'' and ``diseased'' states of the HPA axis as basins of attraction of a dynamical system describing the inhibition of peptide hormones, corticotropin-releasing hormone (CRH) and adrenocorticotropic hormone (ACTH), by circulating glucocorticoids such as cortisol (CORT). Our model includes ultradian oscillations, CRH self-upregulation of CRH release, and distinguishes two components of negative feedback by cortisol on circulating CRH levels: a slow direct suppression of CRH synthesis and a fast indirect effect on CRH release. The slow regulation mechanism mediates external stress-driven transitions between the stable states in novel, intensity, duration, and timing-dependent ways. We find that the timing of traumatic events may be an important factor in determining if and how the hallmarks of depressive disorders will manifest. Our model also suggests a mechanism whereby exposure therapy of stress disorders may act to normalize downstream dysregulation of the HPA axis.

[Effects of electroacupuncture at "Yishu" (EX-B 3) on the relative hormones of HPA axis in rats with type-2 diabetes mellitus].

PubMed

Gao, Shana; Li, Rui; Tian, Huan-huan; Pei, En-shi; Cao, Bing-yan; Wu, Yan

2014-11-01

To observe the intervention effects of electroacupuncture at "Yishu" (EX-B 3) on rats with type-2 diabetes mellitus (T2DM), so as to provide experiment references for acupuncture to treat T2DM. Among seventy male Wistar clean-grade rats, 8 rats were randomly selected into a control group; the rest rats were made T2DM model. Fifty-two rats which were successfully made T2DM model, according to randomized block method, were divided into a model group (10 rats), a medication group (10 rats), an electroacupuncture at "Shenshu" (BL 23) group (11 rats), an electroacupuncture at "Pishu" (BL 20) group (10 rats) and an electroacupuncture at "Yishu" (EX-B 3) group (11 rats). Seven days after successful establishment of model, the rats in the model group were fixed in the self-made rat bag without receiving any treatment; the rats in the medication group, according to body mass (10 mL/kg), were treated with intragastric administration of glimepiride; the rats in all the electroacupuncture groups were treated with electroacupuncture at "Shenshu" (BL 23), "Pishu" (BL 20) and "Yishu" (EX-B 3), respectively. The continuous wave was selected with a frequency of 15 Hz and a current intensity of 4 to 6 mA. The treatment was given 20 min per treatment, once a day, 5 treatments per week for continuous 4 weeks. Before the establishment of model and continuous 4 weeks after the intervention, blood samples were collected from rats' caudal vein, and fasting blood glucose (FBG) was measured with FBG device each week. After the last intervention, the rats were killed and hypothalamus, pituitary and adrenal gland were collected. The colorimetric method was applied to measure the contents of triglyceride (TG), cholesterol (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C); radioimmunoassay was used to test the contents of glycated serum protein (GSP), fasting insulin (FINS), corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and cortin (CORT). Four weeks after the intervention, except that the rat's body mass in the normal group continued to increase, body mass in the model group, medication group and each electroacupuncture group were significantly reduced (P<0.01, P<0.05). Compared with the model group, the FBG in the electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu" (EX-B 3) group were obviously reduced (P<0.05, P<0.01); FBG in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05). The contents of TG, HDL-C and LDL-C in the electroacupuncture at "Yishu" (EX-B 3) group were reduced (P<0.05, P<0.01), the content of TG was significantly lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (both P<0.05), the content of LDL-C was significantly lower than that in electroacupuncture at "Shenshu" (BL 23) group (P<0.05). Insulin sensitivity index (ISI) in the medication group, electroacupuncture at "Pishu" (BL 20) group and electroacupuncture at "Yishu (EX-B 3)" group were evidently increased (P<0.05, P<0.01); ISI in the medication group was lower than that in the electroacupuncture at "Yishu" (EX-B 3) group (P<0.05). The content of CRH in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Shenshu" (BL 23) group (P<0.05, P<0.01); the content of CORT in the electroacupuncture at "Yishu" (EX-B 3) group was lower than that in the medication group and electroacupuncture at "Pishu" (BL 20) group (both P<0.05). Electroacupuncture at "Yishu" (EX-B 3) could reduce the level of CORT to improve the insulin resistance in rats with T2DM, improve insulin sensitivity index, regulate blood lipid metabolism and relieve the hyperactivity of the HPA axis.

Electron heat transport comparison in the Large Helical Device and TJ-II

DOE Office of Scientific and Technical Information (OSTI.GOV)

Garcia, J.; Dies, J.; Castejon, F.

2007-10-15

The electron heat transport in the Large Helical Device (LHD) [K. Ida, T. Shimozuma, H. Funaba et al., Phys. Rev. Lett. 91, 085003 (2003)] and TJ-II [F. Castejon, V. Tribaldos, I. Garcia-Cortes, E. de la Luna, J. Herranz, I. Pastor, T. Estrada, and TJ-II Team, Nucl. Fusion 42, 271 (2002)] is analyzed by means of the TOTAL [K. Yamazaki and T. Amano, Nucl. Fusion 32, 4 (1992)] and PRETOR-Stellarator [J. Dies, F. Castejon, J. M. Fontdecaba, J. Fontanet, J. Izquierdo, G. Cortes, and C. Alejaldre, Proceedings of the 29th European Physical Society Conference on Plasma Physics and Controlled Fusion, Montreux,more » 2002, Europhysics Conference Abstracts, 2004, Vol. 26B, P-5.027] plasma simulation codes and assuming a global transport model mixing GyroBohm-like drift wave model and other drift wave model with shorter wavelength. The stabilization of the GyroBohm-like model by the ExB shear has been also taken into account. Results show how such kind of electron heat transport can simulate experimental evidence in both devices, leading to the electron internal transport barrier (eITB) formation in the LHD and to the so-called 'enhanced heat confinement regimes' in TJ-II when electron density is low enough. Therefore, two sources for the anomalous electron heat transport can coexist in plasmas with eITB; however, for each device the relative importance of anomalous and neoclassical transport can be different.« less

Maternal modulation of novelty effects on physical development.

PubMed

Tang, Akaysha C; Yang, Zhen; Reeb-Sutherland, Bethany C; Romeo, Russell D; McEwen, Bruce S

2012-02-07

Familiarity to the mother and the novelty afforded by the postnatal environment are two contrasting sources of neonatal influence. One hypothesis regarding their relationship is the maternal modulation hypothesis, which predicts that the same neonatal stimulation may have different effects depending on the maternal context. Here we tested this hypothesis using physical development, indexed by body weight, as an endpoint and found that, among offspring of mothers with a high initial swim-stress-induced corticosterone (CORT) response, neonatal novelty exposure induced an enhancement in early growth, and among offspring with mothers of a low initial CORT response, the same neonatal stimulation induced an impairment. At an older age, a novelty-induced increase in body weight was also found among offspring of mothers with high postnatal care reliability and a novelty-induced reduction found among offspring of mothers with low care reliability. These results support a maternal modulation of early stimulation effects on physical development and demonstrate that the maternal influence originates from multiple instead of any singular sources. These results (i) significantly extend the findings of maternal modulation from the domain of cognitive development to the domain of physical development; (ii) offer a unifying explanation for a previously inconsistent literature regarding early stimulation effects on body weight; and (iii) highlight the notion that the early experience effect involves no causal primacy but higher order interactions among the initial triggering events and subsequent events involving a multitude of maternal and nonmaternal influences.

Prevalencia y tamizaje del Trastorno por Déficit de Atención con Hiperactividad en Costa Rica

PubMed Central

Weiss, Nicholas T.; Schuler, Jovita; Monge, Silvia; McGough, James J.; Chavira, Denise; Bagnarello, Monica; Herrera, Luis Diego; Mathews, Carol A.

2015-01-01

Resumen La investigación tuvo como propósito estimar la prevalencia del Trastorno por Déficit de Atención con Hiperactividad (TDAH) en Costa Rica y determinar si la versión en español del cuestionario Swanson Nolan and Pelham Scale IV (SNAP-IV) es un instrumento de tamizaje útil en una población de niños y niñas escolares costarricenses. El instrumento fue entregado a padres y maestros de 425 niños entre 5 y 13 años de edad (promedio = 8.8). Todos fueron evaluados con el instrumento Swanson, Kotkin, Agler, M-Flynn and Pelham Scale (SKAMP). Su diagnóstico fue confirmado con una entrevista clínica. La sensibilidad y la especificidad del SNAP-IV fueron evaluadas como predictores de criterios de diagnóstico según el DSM-IV. La prevalencia puntual en la muestra del TDAH fue del 5%. El tamizaje más preciso lo hizo el SNAP-IV completado por el maestro en un corte de 20%, con una sensibilidad de 96% y una especificidad de un 82%. La sensibilidad de los instrumentos completados por los padres fue más baja que aquella de los maestros. El SNAP-IV completado por las maestras con un corte aislando el 20% de los mayores puntajes categorizó correctamente a un 87% de los sujetos. PMID:22432094

Alarin-induced antidepressant-like effects and their relationship with hypothalamus-pituitary-adrenal axis activity and brain derived neurotrophic factor levels in mice.

PubMed

Wang, Ming; Chen, Qian; Li, Mei; Zhou, Wei; Ma, Tengfei; Wang, Yun; Gu, Shuling

2014-06-01

Alarin is a newly identified member of the galanin family of peptides. Galanin has been shown to exert regulatory effects on depression. Similar to galanin in distribution, alarin is also expressed in the medial amygdala and hypothalamus, i.e., regions interrelated with depression. However, it remains a puzzle whether alarin is involved in depression. Accordingly, we established the depression-like mouse model using behavioral tests to ascertain the possible involvement of alarin, with fluoxetine as a positive control. With the positive antidepressant-like effects of alarin, we further examined its relationship to HPA axis activity and brain-derived neurotrophic factor (BDNF) levels in different brain areas in a chronic unpredictable mild stress (CUMS) paradigm. In the acute studies, alarin produced a dose-related reduction in the immobility duration in tail suspension test (TST) in mice. In the open-field test, intracerebroventricular (i.c.v.) injection of alarin (1.0 nmol) did not impair locomotion or motor coordination in the treated mice. In the CUMS paradigm, alarin administration (1.0 nmol, i.c.v.) significantly improved murine behaviors (FST and locomotor activity), which was associated with a decrease in corticotropin-releasing hormone (CRH) mRNA levels in the hypothalamus, as well as a decline in serum levels of CRH, adrenocorticotropic hormone (ACTH) and corticosterone (CORT), all of which are key hormones of the HPA axis. Furthermore, alarin upregulated BDNF mRNA levels in the prefrontal cortex and hippocampus. These findings suggest that alarin may potentiate the development of new antidepressants, which would be further secured with the identification of its receptor(s). Copyright © 2014 Elsevier Inc. All rights reserved.

Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats

PubMed Central

Lambert, Kelly G.; Hyer, Molly M.; Rzucidlo, Amanda A.; Bergeron, Timothy; Landis, Timothy; Bardi, Massimo

2014-01-01

Emotional resilience enhances an animal's ability to maintain physiological allostasis and adaptive responses in the midst of challenges ranging from cognitive uncertainty to chronic stress. In the current study, neurobiological factors related to strategic responses to uncertainty produced by prediction errors were investigated by initially profiling male rats as passive, active or flexible copers (n = 12 each group) and assigning to either a contingency-trained or non-contingency trained group. Animals were subsequently trained in a spatial learning task so that problem solving strategies in the final probe task, as well-various biomarkers of brain activation and plasticity in brain areas associated with cognition and emotional regulation, could be assessed. Additionally, fecal samples were collected to further determine markers of stress responsivity and emotional resilience. Results indicated that contingency-trained rats exhibited more adaptive responses in the probe trial (e.g., fewer interrupted grooming sequences and more targeted search strategies) than the noncontingent-trained rats; additionally, increased DHEA/CORT ratios were observed in the contingent-trained animals. Diminished activation of the habenula (i.e., fos-immunoreactivity) was correlated with resilience factors such as increased levels of DHEA metabolites during cognitive training. Of the three coping profiles, flexible copers exhibited enhanced neuroplasticity (i.e., increased dentate gyrus doublecortin-immunoreactivity) compared to the more consistently responding active and passive copers. Thus, in the current study, contingency training via effort-based reward (EBR) training, enhanced by a flexible coping style, provided neurobiological resilience and adaptive responses to prediction errors in the final probe trial. These findings have implications for psychiatric illnesses that are influenced by altered stress responses and decision-making abilities (e.g., depression). PMID:24808837

Contingency-based emotional resilience: effort-based reward training and flexible coping lead to adaptive responses to uncertainty in male rats.

PubMed

Lambert, Kelly G; Hyer, Molly M; Rzucidlo, Amanda A; Bergeron, Timothy; Landis, Timothy; Bardi, Massimo

2014-01-01

Emotional resilience enhances an animal's ability to maintain physiological allostasis and adaptive responses in the midst of challenges ranging from cognitive uncertainty to chronic stress. In the current study, neurobiological factors related to strategic responses to uncertainty produced by prediction errors were investigated by initially profiling male rats as passive, active or flexible copers (n = 12 each group) and assigning to either a contingency-trained or non-contingency trained group. Animals were subsequently trained in a spatial learning task so that problem solving strategies in the final probe task, as well-various biomarkers of brain activation and plasticity in brain areas associated with cognition and emotional regulation, could be assessed. Additionally, fecal samples were collected to further determine markers of stress responsivity and emotional resilience. Results indicated that contingency-trained rats exhibited more adaptive responses in the probe trial (e.g., fewer interrupted grooming sequences and more targeted search strategies) than the noncontingent-trained rats; additionally, increased DHEA/CORT ratios were observed in the contingent-trained animals. Diminished activation of the habenula (i.e., fos-immunoreactivity) was correlated with resilience factors such as increased levels of DHEA metabolites during cognitive training. Of the three coping profiles, flexible copers exhibited enhanced neuroplasticity (i.e., increased dentate gyrus doublecortin-immunoreactivity) compared to the more consistently responding active and passive copers. Thus, in the current study, contingency training via effort-based reward (EBR) training, enhanced by a flexible coping style, provided neurobiological resilience and adaptive responses to prediction errors in the final probe trial. These findings have implications for psychiatric illnesses that are influenced by altered stress responses and decision-making abilities (e.g., depression).

Enzyme-Catalyzed Mutation in Breast Cancer

DTIC Science & Technology

2014-08-01

from  ATCC)  and  hTERT-­‐HMEC  (a  gift   from  the  lab  of  Dr.   Vitaly  Polunovsky)  to  over-­‐express  A3B...methylation in mouse primordial germ cells is affected by AID deficiency. Nature. 2010;463:1101-5. [10] Bhutani N , Brady JJ, Damian M, Sacco A...Drier Y, Zou L, Ramos AH, Pugh TJ, Stransky N , Helman E, Kim J, Sougnez C, Ambrogio L, Nickerson E, Shefler E, Cortés ML, Auclair D, Saksena G, Voet D

Applying Psychosocial Theories of Terrorism to the Radicalization Process: A Mapping of De La Corte’s Seven Principles to Homegrown Radicals

DTIC Science & Technology

2011-06-01

branch. In Semitic life, such that led by the Hebrews in ancient times, the woman was considered ritually impure because of her menstruation (Maccoby... Bible left on the beach. He once had a number of Muslim friends, but they‘ve all moved out of California now. My mother was raised Catholic, so she...was, at the very most, the Son of God (since that is what the Bible mistranslates ―Servant of Awareness of difference from other Americans

An Examination of the Historical, Social, Economic, and Political Factors of the Marxist Insurgency in Guatemala.

DTIC Science & Technology

1985-09-16

Lima gave up their hope of instigating another coup and moved to the countryside. There they formed the Revolutionary Movement Alejandro de Leon...Mexico and then the Maya of southern Mexico. In 1524 Cortes’s lieutenant, Pedro de Alvarado, fought his way into what is now Guatemala, and by 1527 had...8217 ~ ~-. .- -• 17 Notes Norman Hammond, "Unearthing the Oldest Known Maya," National Geographic, July 1982, p. 128. Louis de la Haba, "Guatemala, Maya and Modern

Lifelong Aerobic Exercise Reduces the Stress Response in Rats.

PubMed

Pietrelli, A; Di Nardo, M; Masucci, A; Brusco, A; Basso, N; Matkovic, L

2018-04-15

The aim of this study was to analyze the effects of lifelong aerobic exercise (AE) on the adaptive response of the stress system in rats. It is well known that hypothalamic-pituitary-adrenal axis (HPA) activity differs when triggered by voluntary or forced exercise models. Male Wistar rats belonging to exercise (E) or control (C) groups were subjected to chronic AE, and two cutoff points were established at 8 (middle age) and 18 months (old age). Behavioral, biochemical and histopathological studies were performed on the main components/targets of the stress system. AE increased adrenal sensitivity (AS), brain corticosterone (CORT) and corticotropin-releasing factor (CRF), but had no effect on the thymus, adrenal glands (AGs) weight or plasma CORT. In addition, AE exerted no effect on the sympathetic tone, but significantly reduced anxiety-related behavior and emotionality. Aging decreased AS and deregulated neuroendocrine feedback, leading to an anxiogenic state which was mitigated by AE. Histopathological and morphometric analysis of AGs showed no alterations in middle-aged rats but adrenal vacuolization in approximately 20% old rats. In conclusion, lifelong AE did not produce adverse effects related to a chronic stress state. On the contrary, while AE upregulated some components of the HPA axis, it generated an adaptive response to cumulative changes, possibly through different compensatory and/or super compensatory mechanisms, modulated by age. The long-term practice of AE had a strong positive impact on stress resilience so that it could be recommended as a complementary therapy in stress and depression disease. Copyright © 2018 IBRO. Published by Elsevier Ltd. All rights reserved.

Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure

PubMed Central

Barfield, Elizabeth T.; Gerber, Kyle J.; Zimmermann, Kelsey S.; Ressler, Kerry J.; Parsons, Ryan G.

2017-01-01

In humans and rodents, stress promotes habit-based behaviors that can interfere with action–outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent–primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB–ERK42/44 tone determines long-term behavioral outcomes. PMID:29186135

Inhibition of anandamide hydrolysis dampens the neuroendocrine response to stress in neonatal rats subjected to suboptimal rearing conditions.

PubMed

McLaughlin, Ryan Joseph; Verlezza, Silvanna; Gray, Jennifer Megan; Hill, Matthew Nicholas; Walker, Claire-Dominique

2016-01-01

Exposure to stress during early development can exert profound effects on the maturation of the neuroendocrine stress axis. The endocannabinoid (ECB) system has recently surfaced as a fundamental component of the neuroendocrine stress response; however, the effect of early-life stress on neonatal ECB signaling and the capacity to which ECB enhancement may modulate neonatal stress responses is relatively unknown. The present study assessed whether exposure to early-life stress in the form of limited access to nesting/bedding material (LB) from postnatal (PND) day 2 to 9 alters neuroendocrine activity and hypothalamic ECB content in neonatal rats challenged with a novel immobilization stressor. Furthermore, we examined whether inhibition of fatty acid amide hydrolase (FAAH), the enzyme responsible for the degradation of anandamide (AEA) affects neuroendocrine responses in PND10 pups as a function of rearing conditions. Neonatal rats showed a robust increase in corticosterone (CORT) and adrenocorticotropin hormone (ACTH) secretion in response to immobilization stress, which was significantly blunted in pups reared in LB conditions. Accordingly, LB pups exhibited reduced stress-induced Fos immunoreactivity in the paraventricular nucleus of the hypothalamus, with no significant differences in hypothalamic ECB content. Administration of the FAAH inhibitor URB597 (0.3 mg/kg, ip) 90 min prior to immobilization stress significantly dampened stress-induced CORT release, but only in pups reared in LB conditions. These results suggest that rearing in restricted bedding conditions dampens the neuroendocrine response to stress, while augmenting AEA mitigates stress-induced alterations in glucocorticoid secretion preferentially in pups subjected to early-life stress.

Regulation of actions and habits by ventral hippocampal trkB and adolescent corticosteroid exposure.

PubMed

Barfield, Elizabeth T; Gerber, Kyle J; Zimmermann, Kelsey S; Ressler, Kerry J; Parsons, Ryan G; Gourley, Shannon L

2017-11-01

In humans and rodents, stress promotes habit-based behaviors that can interfere with action-outcome decision-making. Further, developmental stressor exposure confers long-term habit biases across rodent-primate species. Despite these homologies, mechanisms remain unclear. We first report that exposure to the primary glucocorticoid corticosterone (CORT) in adolescent mice recapitulates multiple neurobehavioral consequences of stressor exposure, including long-lasting biases towards habit-based responding in a food-reinforced operant conditioning task. In both adolescents and adults, CORT also caused a shift in the balance between full-length tyrosine kinase receptor B (trkB) and a truncated form of this neurotrophin receptor, favoring the inactive form throughout multiple corticolimbic brain regions. In adolescents, phosphorylation of the trkB substrate extracellular signal-regulated kinase 42/44 (ERK42/44) in the ventral hippocampus was also diminished, a long-term effect that persisted for at least 12 wk. Administration of the trkB agonist 7,8-dihydroxyflavone (7,8-DHF) during adolescence at doses that stimulated ERK42/44 corrected long-lasting corticosterone-induced behavioral abnormalities. Meanwhile, viral-mediated overexpression of truncated trkB in the ventral hippocampus reduced local ERK42/44 phosphorylation and was sufficient to induce habit-based and depression-like behaviors. Together, our findings indicate that ventral hippocampal trkB is essential to goal-directed action selection, countering habit-based behavior otherwise facilitated by developmental stress hormone exposure. They also reveal an early-life sensitive period during which trkB-ERK42/44 tone determines long-term behavioral outcomes.

Estradiol stimulates an anti-translocation expression pattern of glucocorticoid co-regulators in a hippocampal cell model

PubMed Central

Malviya, Sanjana A.; Kelly, Sean D.; Greenlee, Megan M.; Eaton, Douglas C.; Duke, Billie Jeanne; Bourke, Chase H.; Neigh, Gretchen N.

2013-01-01

A consistent clinical finding in patients with major depressive disorder (MDD) is hyperactivity of the hypothalamic–pituitary–adrenal (HPA) axis, the system in the body that facilitates the response to stress. It has been suggested that alterations in glucocorticoid receptor (GR)-mediated feedback prolong activation of the HPA axis, leading to the dysfunction observed in MDD. Additionally, the risk for developing MDD is heightened by several risk factors, namely gender, genetics and early life stress. Previous studies have demonstrated that GR translocation is sexually dimorphic and this difference may be facilitated by differential expression of GR co-regulators. The purpose of this study was to determine the extent to which ovarian hormones alter expression of GR and its co-regulators, Fkbp5 and Ppid, in HT-22 hippocampal neurons. The impact of corticosterone (cort), estradiol (E2), and progesterone (P4) treatments on the expression of the genes Nr3c1, Ppid, and Fkbp5 was assessed in HT-22 hippocampal neurons. Treatment of cells with increasing doses of cort increased the expression of Fkbp5, an effect that was potentiated by E2. Exposure of HT-22 cells to E2 decreased the expression of Ppid and simultaneous exposure to E2 and P4 had combinatory effects on Ppid expression. The effects of E2 on Ppid extend previous work which demonstrated that serum E2 concentrations correlate with hippocampal Ppid expression in female rats. The results presented here illustrate that E2 generates an anti-translocation pattern of GR co-regulators in hippocampal cells. PMID:23541378

Cross-linkers both drive and brake cytoskeletal remodeling and furrowing in cytokinesis.

PubMed

Descovich, Carlos Patino; Cortes, Daniel B; Ryan, Sean; Nash, Jazmine; Zhang, Li; Maddox, Paul S; Nedelec, Francois; Maddox, Amy Shaub

2018-03-01

Cell shape changes such as cytokinesis are driven by the actomyosin contractile cytoskeleton. The molecular rearrangements that bring about contractility in nonmuscle cells are currently debated. Specifically, both filament sliding by myosin motors, as well as cytoskeletal cross-linking by myosins and nonmotor cross-linkers, are thought to promote contractility. Here we examined how the abundance of motor and nonmotor cross-linkers affects the speed of cytokinetic furrowing. We built a minimal model to simulate contractile dynamics in the Caenorhabditis elegans zygote cytokinetic ring. This model predicted that intermediate levels of nonmotor cross-linkers are ideal for contractility; in vivo, intermediate levels of the scaffold protein anillin allowed maximal contraction speed. Our model also demonstrated a nonlinear relationship between the abundance of motor ensembles and contraction speed. In vivo, thorough depletion of nonmuscle myosin II delayed furrow initiation, slowed F-actin alignment, and reduced maximum contraction speed, but partial depletion allowed faster-than-expected kinetics. Thus, cytokinetic ring closure is promoted by moderate levels of both motor and nonmotor cross-linkers but attenuated by an over-abundance of motor and nonmotor cross-linkers. Together, our findings extend the growing appreciation for the roles of cross-linkers in cytokinesis and reveal that they not only drive but also brake cytoskeletal remodeling. © 2018 Descovich, Cortes, et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

The Antidepressant and Cognitive Improvement Activities of the Traditional Chinese Herb Cistanche

PubMed Central

Wang, Haizhen

2017-01-01

More than ten percent of people suffer from at least one episode of depression and related mental disorders in a lifetime, and depression and related mental disorders are one of the world's greatest public health problems. A multiple system theory holds that dysregulation of the multiple systems underlies the pathogenesis of depression and related mental disorders, and new therapies based on the multiple system dysregulation theory are urgently needed. In this study, the antidepressant effect of decoction from herb Cistanche deserticola Y.C.Ma and Cistanche tubulosa was examined. Herb Cistanche decoction reduced the immobility period significantly in the mouse tail suspension test. Mice treated with herb decoction showed an improved ability of spatial learning and memory in the Morris water maze test. Groups treated herb decoction displayed a downregulated monoamine oxidase (MAO) activity; the dopamine (DA) concentration in the brain was upregulated, indicating herb Cistanche decoction improved the nerve excitability; the serum concentration of corticosterone (CORT) was downregulated, showing that mice benefited from a reduced stress level. Hence, the antidepressant efficacy and mechanism of traditional Chinese herb Cistanche were explored in this study. Herb Cistanche showed a potential to be developed as a complementary and alternative therapy for depression. PMID:28744316

Delayed Memory Effects after Intense Stress in Special Forces Candidates: Exploring Path Processes between Cortisol Secretion and Memory Recall

DTIC Science & Technology

2013-05-01

Stress Y ROCF (I & P) M2 NASA TLX Panel B M1 ∆CORT Figure 1. Panel A represents a direct effect of the independent (X; stress treatment) on the...mediators (M1 and M2), and path indices (a1, a2, b1, b2, and c 0). DCORT, change in salivary cortisol concentration; NASA TLX , National Aeronautics...tive mental workload: A comparison of SWAT, NASA - TLX , and workload profile methods. Appl Psychol Int Rev 53:61–86. Salehi B, Cordero I, Sandi C. 2010

New large outburst of 29P/Schwassmann-Wachmann 1

NASA Astrophysics Data System (ADS)

Kidger, Mark

2010-04-01

Mark Kidger reports on behalf of the "Observadores_cometas Group" that a major new outburst of Comet 29P/Schwassmann-Wachmann has occurred two days before the Herschel Space Observatory is due to observe the comet. The outburst was first reported on 2010 Apr. 16, 19:22UT at R=12.8 in a 10" square aperture by Estevé Cortés and the Grup d'Astronomia de Mataró (MPC A06, Mataró, Spain), having been last seen at R=16.18 by José Ramón Vidal (MPC 945, Gijón, Spain) on 2010 Apr.

Cocoa and heart health: a historical review of the science.

PubMed

Pucciarelli, Deanna L

2013-09-26

The medicinal use of cocoa has a long history dating back almost five hundred years when Hernán Cortés's first experienced the drink in Mesoamerica. Doctors in Europe recommended the beverage to patients in the 1700s, and later American physicians followed suit and prescribed the drink in early America--ca. 1800s. This article delineates the historic trajectory of cocoa consumption, the linkage between cocoa's bioactive-mechanistic properties, paying special attention to nitric oxides role in vasodilation of the arteries, to the current indicators purporting the benefits of cocoa and cardiovascular health.

Reliability and availability modeling of coupled communication networks - A simplified modeling approach

NASA Technical Reports Server (NTRS)

Shooman, Martin L.; Cortes, Eladio R.

1991-01-01

The network-complexity of LANs and of LANs that are interconnected by bridges and routers poses a challenging reliability-modeling problem. The present effort toward these problems' solution attempts to simplify them by reducing their number of states through truncation and state merging, as suggested by Shooman and Laemmel (1990). Through the use of state merging, it becomes possible to reduce the Bateman-Cortes 161 state model to a two state model with a closed-form solution. In the case of coupled networks, a technique which allows for problem-decomposition must be used.

Cocoa and Heart Health: A Historical Review of the Science

PubMed Central

Pucciarelli, Deanna L.

2013-01-01

The medicinal use of cocoa has a long history dating back almost five hundred years when Hernán Cortés’s first experienced the drink in Mesoamerica. Doctors in Europe recommended the beverage to patients in the 1700s, and later American physicians followed suit and prescribed the drink in early America―ca. 1800s. This article delineates the historic trajectory of cocoa consumption, the linkage between cocoa’s bioactive-mechanistic properties, paying special attention to nitric oxides role in vasodilation of the arteries, to the current indicators purporting the benefits of cocoa and cardiovascular health. PMID:24077240

Impact of Medication Adherence on Mortality and Cardiovascular Morbidity: Protocol for a Population-Based Cohort Study.

PubMed

Giner-Soriano, Maria; Sotorra Figuerola, Gerard; Cortés, Jordi; Pera Pujadas, Helena; Garcia-Sangenis, Ana; Morros, Rosa

2018-03-09

Cardiovascular disease (CVD) is a group of disorders of the heart and blood vessels, such as coronary heart disease (CHD), cerebrovascular disease, and peripheral artery disease. CVD is the leading threat to global health, whether measured by mortality, morbidity, or economic cost. Long-term administration of aspirin, statins, beta-blockers, and angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers improves survival in patients with stablished coronary heart disease. Nevertheless, adherence to prescribed medication is poor for long-term drug treatment. We aim to assess the relationship between adherences to the four pharmacological groups recommended for secondary prevention and the clinical outcomes of cardiovascular morbidity and mortality in patients with established CHD according to the level of adherence to these drugs in a population of incident cases of acute coronary syndrome (ACS). Population-based cohort study of patients with a first episode of ACS during 2006-2015 in the Information System for Research in Primary Care (SIDIAP) database. We will estimate adherence to these drugs. The primary endpoint is a composite of all-cause mortality, ACS, and ischaemic stroke. Bivariate analyses will be performed estimating odds ratios for categorical variables and mean differences for continuous variables. Hazard ratios for adherences will be calculated for outcome events using Cox proportional hazard regression models, and proportionality of hazards assumption will be tested. We expect to estimate adherence to all four study treatments, the incidence of MACE, and to analyze if this incidence is associated with the level of drug adherence. We expect to find that adherent patients have a lower risk of the primary endpoints compared with nonadherent patients. This study protocol was classified as EPA-OD by the AEMPS (IJG-EST-2017-01-2017-01, 07/04/2017) and registered in the EU PAS register (EUPAS19017, 09/05/2017). ©Maria Giner-Soriano, Gerard Sotorra Figuerola, Jordi Cortés, Helena Pera Pujadas, Ana Garcia-Sangenis, Rosa Morros. Originally published in JMIR Research Protocols (http://www.researchprotocols.org), 09.03.2018.

Reversing the irreversible: From limit cycles to emergent time symmetry

NASA Astrophysics Data System (ADS)

Cortês, Marina; Smolin, Lee

2018-01-01

In 1979 Penrose hypothesized that the arrows of time are explained by the hypothesis that the fundamental laws are time irreversible [R. Penrose, in General Relativity: An Einstein Centenary Survey (1979)]. That is, our reversible laws, such as the standard model and general relativity are effective, and emerge from an underlying fundamental theory which is time irreversible. In [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007; 90, 044035 (2014), 10.1103/PhysRevD.90.044035; 93, 084039 (2016), 10.1103/PhysRevD.93.084039] we put forward a research program aiming at realizing just this. The aim is to find a fundamental description of physics above the Planck scale, based on irreversible laws, from which will emerge the apparently reversible dynamics we observe on intermediate scales. Here we continue that program and note that a class of discrete dynamical systems are known to exhibit this very property: they have an underlying discrete irreversible evolution, but in the long term exhibit the properties of a time reversible system, in the form of limit cycles. We connect this to our original model proposal in [M. Cortês and L. Smolin, Phys. Rev. D 90, 084007 (2014), 10.1103/PhysRevD.90.084007], and show that the behaviors obtained there can be explained in terms of the same phenomenon: the attraction of the system to a basin of limit cycles, where the dynamics appears to be time reversible. Further than that, we show that our original models exhibit the very same feature: the emergence of quasiparticle excitations obtained in the earlier work in the space-time description is an expression of the system's convergence to limit cycles when seen in the causal set description.

Effects of chronic social isolation on Wistar rat behavior and brain plasticity markers.

PubMed

Djordjevic, Jelena; Djordjevic, Ana; Adzic, Miroslav; Radojcic, Marija B

2012-01-01

Chronic stress is a contributing risk factor in the development of psychiatric illnesses, including depressive disorders. The mechanisms of their psychopathology are multifaceted and include, besides others, alterations in the brain plasticity. Previously, we investigated the effects of chronic social stress in the limbic brain structures of Wistar rats (hippocampus, HIPPO, and prefrontal cortex, PFC) and found multiple characteristics that resembled alterations described in some clinical studies of depression. We extended our investigations and followed the behavior of stressed animals by the open field test (OFT) and forced swimming test (FST), and the expression and polysialylation of synaptic plasticity markers, neural cell adhesion molecule (NCAM) and L1, in the HIPPO and PFC. We also determined the adrenal gland mass and plasma corticosterone (CORT) as a terminal part of the hypothalamic-pituitary-adrenal axis activity. Our data indicated that stressed animals avoided the central zone in the OFT and displayed decreased swimming, but prolonged immobility in the FST. The animals exhibited marked hypertrophy of the adrenal gland cortex, in spite of decreased serum CORT. Simultaneously, the stressed animals exhibited an increase in NCAM mRNA expression in the HIPPO, but not in the PFC. The synaptosomal NCAM of the HIPPO was markedly polysialylated, while cortical PSA-NCAM was significantly decreased. The results showed that chronic social isolation of Wistar rats causes both anxiety-like and depression-like behavior. These alterations are parallel with molecular changes in the limbic brain, including diminished NCAM sialylation in the PFC. Together with our previous results, the current observations suggest that a chronic social isolation model may potentially be used to study molecular mechanisms that underlie depressive symptomatology. Copyright © 2012 S. Karger AG, Basel.

Personality profiles and risk diet behaviors--a case-control study on teenagers from Timis County, Romania.

PubMed

Petrescu, Cristina; Vlaicu, Brigitha

2014-01-01

In the study we conducted we aimed at investigating the relation between personality profiles and risk diet behaviors in teenagers. This study was a case-control one and we applied 2 questionnaires (Freiburg Personality Inventory--FPI with 212 items) and CORT 2004 (items Q94-Q116 of diet behavior) on a sample of 2908 teenagers (51.5% girls and 48.5% boys). Cronbach's alpha index was 0.802 for FPI and 0.730 for items Q101-Q109 of CORT. Personality profiles were built by an Excel 2003 Program. Statistical analysis was realized with SPSS 16 program applying Chi square (chi2) and gamma (gamma) correlation. Personality features of teenagers with high and without risk diet behavior were analyzed. Results obtained: personality profiles and statistical results indicated the existence of a significant statistical difference of aggressiveness and domination between teenagers with high and no consumption of butter and/or lard (Q103) (chi2 = 6.872, Sig. 0.032 and chi2 = 6.922, Sig. 0.031 respectively), of juices from the market (Q106) (chi2 = 9.055, Sig. 0.011 and chi2 = 14.571, Sig. 0.001 respectively). Aggressiveness correlated with consumption of fried potatoes (Q109) (chi2 = 6.144, Sig. 0.046) too. Correlation gamma indicated direct proportional relations of aggressiveness with: Q103 (gamma = 0.215, Sig. 0.017), Q106 (gamma = 0.224, Sig. 0.004), Q109 (gamma = 0.242, Sig. 0.012); and of domination with: Q103 (gamma = 0.234, Sig. 0.008), Q106 (gamma = 0.073, Sig. 0.000). In conclusion, there is a direct proportional relation between consumption of: butter/lard, juices from the market and teenagers' aggressiveness, domination; and a similar relation between consumption of fried potatoes and aggressiveness.

Neonatal vaginal irritation results in long-term visceral and somatic hypersensitivity and increased hypothalamic–pituitary–adrenal axis output in female mice

PubMed Central

Pierce, Angela N.; Zhang, Zhen; Fuentes, Isabella M.; Wang, Ruipeng; Ryals, Janelle M.; Christianson, Julie A.

2015-01-01

Abstract Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. Serum corticosterone (CORT), mast cell degranulation, and corticotropin-releasing factor receptor 1 (CRF1) expression were measured as indicators of peripheral HPA axis activation. Colorectal and hind paw sensitivity were measured to determine cross-sensitization resulting from NVI. Adult NVI mice had significantly larger visceromotor response during VBD than naive mice. TRPA1 protein expression was significantly elevated in the vagina, and calcium transients evoked by mustard oil (TRPA1 ligand) or capsaicin (TRPV1 ligand) were significantly decreased in dorsal root ganglion from NVI mice, despite displaying increased depolarization-evoked calcium transients. Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation. PMID:26098441

Sex-Specific Effects of Unpredictable Variable Prenatal Stress: Implications for Mammalian Developmental Programming During Spaceflight

NASA Technical Reports Server (NTRS)

Talyansky, Y.; Moyer, E. L.; Oijala, E.; Baer, L. A.; Ronca, A. E.

2016-01-01

During adaptation to the microgravity environment, adult mammals experience stress mediated by the Hypothalamic-Pituitary-Adrenal axis. In our previous studies of pregnant rats exposed to 2-g hypergravity via centrifugation, we reported decreased corticosterone and increased body mass and leptin in adult male, but not female, offspring. In this study, we utilized Unpredictable Variable Prenatal Stress to simulate the stressors of spaceflight by exposing dams to different stressors. Stress response modulation occurs via both positive and negative feedback in the hypothalamus, anterior pituitary gland, and adrenal cortex resulting in the differential release of corticosterone (CORT), a murine analog to human cortisol.