Impact of chronic stressors on the anxiety profile of pregnant rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of exercise training on stress-induced vascular reactivity alterations: role of nitric oxide and prostanoids

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adolescent vulnerability to cardiovascular consequences of chronic social stress: Immediate and long-term effects of social isolation during adolescence

It has been demonstrated that disruption of social bonds and perceived isolation (loneliness) are associated with an increased risk of cardiovascular morbidity and mortality. Adolescence is proposed as a period of vulnerability to stress. Nevertheless, the impact of chronic social stress during this ontogenic period in cardiovascular function is poorly understood. Therefore, the purpose of this study was to compare the impact in cardiovascular function of social isolation for 3 weeks in adolescent and adult male rats. Also, the long-term effects of social isolation during adolescence were investigated longitudinally. Social isolation reduced body weight in adolescent, but not in adult animals. Disruption of social bonds during adolescence increased arterial pressure without affecting heart rate and pulse pressure (PP). Nevertheless, social isolation in adulthood reduced systolic arterial pressure and increased diastolic arterial pressure, which in turn decreased PP without affecting mean arterial pressure. Cardiovascular changes in adolescents, but not adults, were followed by facilitation of both baroreflex sensitivity and vascular reactivity to the vasodilator agent acetylcholine. Vascular responsiveness to either the vasodilator agent sodium nitroprusside or the vasoconstrictor agent phenylephrine was not affected by social isolation. Except for the changes in body weight and baroreflex sensitivity, all alterations evoked by social isolation during adolescence were reversed in adulthood after moving animals from isolated to collective housing. These findings suggest a vulnerability of adolescents to the effects of chronic social isolation in cardiovascular function. However, results indicate minimal cardiovascular consequences in adulthood of disruption of social bonds during adolescence. © 2015 Wiley Periodicals, Inc. Develop Neurobiol, 2015.

The strategic application of elecytolyte balance to minimize heat stress in broilers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Strategic feed formulation for relation of electrolytes to promote performance and prevent heat stress in broilers

An experiment was conducted to evaluate the impact in relation of dietary electrolytes, based on changes in the balance Na+K-Cl (DEB) and the ratio (K+Cl)/Na (DER) on the performance and survival of broilers subjected to acute heat stress. A total of 1575 male broiler chicks from 1 to 46 d of age were allocated in a 5x3 factorial arrangement in a completely randomized design, totaling of 15 treatments with 3 replicates of 35 birds each. The treatments consisted of 5 diets with electrolyte balances, arising from combinations DEB/DER (150/3, 250/2, 250/3, 250/4 and 350/3), associated with different times of application or not of the acute heat stress on birds at 25 and 36 d old. All diets were cornsoybean meal based and formulated to meet or exceed NRC requirements. Chicks had ad libitum access to feed and water in floor pens with wood shavings as litter. It was possible to verify that a DEB of 250 mEq/kg and a DER very close to the 3:1 providing a more nutritionally adequate diet. There was, however, the impossibility of obtaining a more suitable electrolyte ratio for a very low DEB (150 mEq/kg) or very high (350 mEq/kg) and also, to a very narrow DER (2:1) or very wide (4:1), due to an unfavorable performance and survival rate of birds in these conditions electrolytes adjustments of K, Na and Cl. There was clear indication, with significant difference (P < 0.05), that the DER has the potential to improve the performance of broilers, since simultaneous adjustment made in DEB, even in conditions of acute stress. The results of performance and survival rate of this study also indicate clearly that DER could not replace the DEB, and vice versa, in practical diets for broilers. Therefore, it can be affirmed that the strategic formulation of the correct electrolyte balance for DEB and DER enhances the performance and is able to prevent the effect of heat stress in broiler chickens, leading to better performance and survival.

Biochemical changes during the induction of mineral stress in plants of bell pepper cultivated in fertigation system

The greenhouse production associated with the fertigation management, have established in Brazil as economical alternative for several horticultural species. With this strategy this study had as aim to evaluate possible impacts in the metabolism of plants of bell pepper (Capsicum annuum L.; cv Elisa) in response to the increase of mineral concentration in the soil. During the experiments, the some nutrient concentrations were altered, to obtain high values of electric conductivity (EC) in the soil solution. The EC values commonly observed in the traditional fertigation system were adopted, as control. It was also verified the possibility of reduction of the mineral stress impact by the application of organic matter in the soil. Parameters of the antioxidative response system, as the superoxide dismutase (SOD) and catalase enzyme activities besides the proline content were evaluated to measure the extension of the saline stress and their effects on the plants. The increase of EC of the soil induced to the increase of the proline concentration and the SOD activity. Unexpectedly, it was verified that the saline stress inhibited the activity of the enzyme catalase. It was also concluded that the monitoring of EC of the soil is an indispensable tool to reach success in the fertigation system and that the study of the activity of the enzymes of the antioxidative response system, and the proline contents can be assumed as indicators in of the levels of stress in bell pepper plants (Capsicum annuum L.; cv Elisa).

Comparison of Endocrine Response to Stress Between Captive-Raised and Wild-Caught Bighorn Sheep

Stress hormones in Rocky Mountain bighorn sheep (Ovis canadensis canadensis), produced in response to environmental changes, road development, or high population density, may impact their immune systems to a threshold level that predisposes them to periodic, large-scale mortality. We compared the stress response to a novel environmental situation and repeated handling between bighorn sheep born and raised in captivity (CR) and bighorn sheep born in the wild (WC) and brought into captivity. We measured plasma epinephrine, norepinephrine, cortisol, and fecal glucocorticoid metabolites (FGM). Three weeks after each group’s arrival we used a one-time drop-net event to elicit an acute stress response, and we collected blood samples from each sheep over 35 minutes, as well as one fecal sample. We collected blood and fecal samples from both groups on 7 other occasions over the subsequent 6 months. We also collected fecal samples from the pen at approximately 24-hour intervals for 3 days following every handling event to monitor the stress response to handling. We found that CR sheep had a stronger autonomic nervous system response than WC sheep, as measured by epinephrine and norepinephrine levels, but we found a very similar hypothalamic–pituitary–adrenal axis (HPA) response, measured by cortisol levels, to the acute stress event of a drop-net restraint. We also found that once the WC sheep had acclimated, as indicated by the return to the initial baseline FGM levels within 12 weeks, the CR and WC groups’ HPA responses to sampling events were not significantly different from one another. Fecal samples can provide a noninvasive mechanism for managers to monitor baseline FGM for a given herd. Using long-term monitoring of FGM rather than values from a single point in time may allow managers to correlate these levels to outside influences on the herd and better understand the impacts of management changes, population density, or increased human developments on the health of the sheep population.

Impact of biannual rossby waves on the Indian Ocean Dipole

Topex/Poseidon sea surface height anomalies during 1993-2002 are decomposed using 2-D finite impulse response filters which showed biannual Rossby waves (BRWs) in the equatorial Indian Ocean (peak at 1.5 degrees S) and in the southern tropical Indian Ocean (peak at 10.5 degrees S) during Indian Ocean Dipole (IOD) years. Anomalous downwelling BRWs in the equatorial Indian Ocean triggered by the wind stress curl-induced Ekman pumping near the eastern boundary started propagating westward from the eastern boundary in July/August 1993 and 1996, i.e., more than one year prior to the formation of the IOD events of 1994 and 1997 respectively. These strong downwelling signals reach the western equatorial Indian Ocean during the peak dipole time.

Calorie restriction increases cerebral mitochondrial respiratory capacity in a NO center dot-mediated mechanism: Impact on neuronal survival

Calorie restriction (CR) enhances animal life span and prevents age-related diseases, including neurological decline. Recent evidence suggests that a mechanism involved in CR-induced life-span extension is NO-stimulated mitochondrial biogenesis. We examine here the effects of CR on brain mitochondrial content. CR increased eNOS and nNOS and the content of mitochondria] proteins (cytochrome c oxidase, citrate synthase, and mitofusin) in the brain. Furthermore, we established an in vitro system to study the neurological effects of CR using serum extracted from animals on this diet. In cultured neurons, CR serum enhanced nNOS expression and increased levels of nitrite (a NO product). CR serum also enhanced the levels of cytochrome c oxidase and increased citrate synthase activity and respiratory rates in neurons. CR serum effects were inhibited by L-NAME and mimicked by the NO donor SNAP. Furthermore, both CR sera and SNAP were capable of improving neuronal survival. Overall, our results indicate that CR increases mitochondrial biogenesis in a NO-mediated manner, resulting in enhanced reserve respiratory capacity and improved survival in neurons. (C) 2012 Elsevier Inc. All rights reserved.

Studying the genetic basis of drought tolerance in sorghum by managed stress trials and adjustments for phenological and plant height differences

Managed environments in the form of well watered and water stressed trials were performed to study the genetic basis of grain yield and stay green in sorghum with the objective of validating previously detected QTL. As variations in phenology and plant height may influence QTL detection for the target traits, QTL for flowering time and plant height were introduced as cofactors in QTL analyses for yield and stay green. All but one of the flowering time QTL were detected near yield and stay green QTL. Similar co-localization was observed for two plant height QTL. QTL analysis for yield, using flowering time/plant height cofactors, led to yield QTL on chromosomes 2, 3, 6, 8 and 10. For stay green, QTL on chromosomes 3, 4, 8 and 10 were not related to differences in flowering time/plant height. The physical positions for markers in QTL regions projected on the sorghum genome suggest that the previously detected plant height QTL, Sb-HT9-1, and Dw2, in addition to the maturity gene, Ma5, had a major confounding impact on the expression of yield and stay green QTL. Co-localization between an apparently novel stay green QTL and a yield QTL on chromosome 3 suggests there is potential for indirect selection based on stay green to improve drought tolerance in sorghum. Our QTL study was carried out with a moderately sized population and spanned a limited geographic range, but still the results strongly emphasize the necessity of corrections for phenology in QTL mapping for drought tolerance traits in sorghum.

Impact of hypoxia on IGF-I, IGF-II, IGFBP-3, ALS and IGFBP-1 regulation and on IGF1R gene expression in children

Hypoxia is one of many factors involved in the regulation of the IGF system. However, no information is available regarding the regulation of the IGF system by acute hypoxia in humans. Objective: The aim of this study was to evaluate the effect of acute hypoxia on the IGF system of children. Design: Twenty-seven previously health children (14 boys and 13 girls) aged 15 days to 9.5 years were studied in two different situations: during a hypoxemic state (HS) due to acute respiratory distress and after full recovery to a normoxemic state (NS). In these two situations oxygen saturation was assessed with a pulse-oximeter and blood samples were collected for serum IGF-I, IGF-II, IGFBP-1, IGFBP-3, ALS and insulin determination by ELISA; fluoroimmunometric assay determination for GH and also for IGF1R gene expression analysis in peripheral lymphocytes by quantitative real-time PCR. Data were paired and analyzed by the Wilcoxon non-parametric test. Results: Oxygen saturation was significantly lower during HS than in NS (P<0.0001). IGF-I and IGF-II levels were lower during HS than in NS (P<0.0001 and P=0.0004. respectively). IGFBP-3 levels were also lower in HS than in NS (P=0.0002) while ALS and basal GH levels were higher during HS (P=0.0015 and P=0.014, respectively). Moreover, IGFBP-1 levels were higher during HS than in NS (P=0.004). No difference was found regarding insulin levels. The expression of IGF1R mRNA as 2(-Delta Delta CT) was higher during HS than in NS (P=0.03). Conclusion: The above results confirm a role of hypoxia in the regulation of the IGF system also in humans. This effect could be direct on the liver and/or mediated by GH and it is not restricted to the hepatocytes but involves other cell lines. During acute hypoxia a combination of alterations usually associated with reduced IGF action was observed. The higher expression of IGF1R mRNA may reflect an up-regulation of the transcriptional process. (C) 2012 Elsevier Ltd. All rights reserved.

An analytic method to compute the stress dependence on the dimensions and its influence in the characteristics of triple gate devices

Triple-gate devices are considered a promising solution for sub-20 nm era. Strain engineering has also been recognized as an alternative due to the increase in the carriers mobility it propitiates. The simulation of strained devices has the major drawback of the stress non-uniformity, which cannot be easily considered in a device TCAD simulation without the coupled process simulation that is time consuming and cumbersome task. However, it is mandatory to have accurate device simulation, with good correlation with experimental results of strained devices, allowing for in-depth physical insight as well as prediction on the stress impact on the device electrical characteristics. This work proposes the use of an analytic function, based on the literature, to describe accurately the strain dependence on both channel length and fin width in order to simulate adequately strained triple-gate devices. The maximum transconductance and the threshold voltage are used as the key parameters to compare simulated and experimental data. The results show the agreement of the proposed analytic function with the experimental results. Also, an analysis on the threshold voltage variation is carried out, showing that the stress affects the dependence of the threshold voltage on the temperature. (C) 2011 Elsevier Ltd. All rights reserved.

Impact of Corticosterone Treatment on Spontaneous Seizure Frequency and Epileptiform Activity in Mice with Chronic Epilepsy

Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone ( CORT) would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus. We monitored video-EEG activity in pilocarpine-treated mice 24/7 for a period of four or more weeks, during which animals were serially treated with CORT or vehicle. CORT increased the frequency and duration of epileptiform events within the first 24 hours of treatment, and this effect persisted for up to two weeks following termination of CORT injections. Interestingly, vehicle injection produced a transient spike in CORT levels - presumably due to the stress of injection - and a modest but significant increase in epileptiform activity. Neither CORT nor vehicle treatment significantly altered seizure frequency; although a small subset of animals did appear responsive. Taken together, our findings indicate that treatment of epileptic animals with exogenous CORT designed to mimic chronic stress can induce a persistent increase in interictal epileptiform activity.

Effects of Repeated Stress on Distal Airway Inflammation, Remodeling and Mechanics in an Animal Model of Chronic Airway Inflammation

Background/Aims: Epidemiological studies suggest that stress has an impact on asthmatic exacerbations. We evaluated if repeated stress, induced by forced swimming, modulates lung mechanics, distal airway inflammation and extracellular matrix remodeling in guinea pigs with chronic allergic inflammation. Methods: Guinea pigs were submitted to 7 ovalbumin or saline aerosols (1-5 mg/ml during 4 weeks; OVA and SAL groups). Twenty-four hours after the 4th inhalation, guinea pigs were submitted to the stress protocol 5 times a week during 2 weeks (SAL-S and OVA-S groups). Seventy-two hours after the 7th inhalation, guinea pigs were anesthetized and mechanically ventilated. Resistance and elastance of the respiratory system were obtained at baseline and after ovalbumin challenge. Lungs were removed, and inflammatory and extracellular matrix remodeling of distal airways was assessed by morphometry. Adrenals were removed and weighed. Results: The relative adrenal weight was greater in stressed guinea pigs compared to non-stressed animals (p < 0.001). Repeated stress increased the percent elastance of the respiratory system after antigen challenge and eosinophils and lymphocytes in the OVA-S compared to the OVA group (p < 0.001, p = 0.003 and p < 0.001). Neither collagen nor elastic fiber contents were modified by stress in sensitized animals. Conclusions: In this animal model, repeated stress amplified bronchoconstriction and inflammatory response in distal airways without interfering with extracellular matrix remodeling. Copyright (C) 2011 S. Karger AG, Basel

Evidence for premature aging due to oxidative stress in iPSCs from Cockayne syndrome

Cockayne syndrome (CS) is a human premature aging disorder associated with neurological and developmental abnormalities, caused by mutations mainly in the CS group B gene (ERCC6). At the molecular level, CS is characterized by a deficiency in the transcription-couple DNA repair pathway. To understand the role of this molecular pathway in a pluripotent cell and the impact of CSB mutation during human cellular development, we generated induced pluripotent stem cells (iPSCs) from CSB skin fibroblasts (CSB-iPSC). Here, we showed that the lack of functional CSB does not represent a barrier to genetic reprogramming. However, iPSCs derived from CSB patients fibroblasts exhibited elevated cell death rate and higher reactive oxygen species (ROS) production. Moreover, these cellular phenotypes were accompanied by an up-regulation of TXNIP and TP53 transcriptional expression. Our findings suggest that CSB modulates cell viability in pluripotent stem cells, regulating the expression of TP53 and TXNIP and ROS production.