Corticosterone Concentrations Research Articles

Potential Role of Bmal1 in Lipopolysaccharide-Induced Depression-Like Behavior and its Associated "Inflammatory Storm".

Inflammation plays an important role in the pathogenesis of depression; however, the underlying mechanisms remain unclear. Apart from the disordered circadian rhythm in animal models and patients with depression, dysfunction of clock genes has been reported to be involved with the progress of inflammation. This study aimed to investigate the role of circadian clock genes, especially brain and muscle ARNT-like 1 (Bmal1), in the linkage between inflammation and depression. Lipopolysaccharide (LPS)-challenged rats and BV2 cells were used in the present study. Four intraperitoneal LPS injections of 0.5mg/kg were administered once every other day to the rats, and BV2 cells were challenged with LPS for 24h at the working concentration of 1mg/L, with or without the suppression of Bmal1 via small interfering RNA. The results showed that LPS could successfully induce depression-like behaviors and an "inflammatory storm" in rats, as indicated by the increased immobility time in the forced swimming test and the decreased saccharin preference index in the saccharin preference test, together with hyperactivity of the hypothalamic-pituitary-adrenal axis, hyperactivation of astrocyte and microglia, and increased peripheral and central abundance of tumor necrosis factor-α, interleukin 6, and C-reactive protein. Moreover, the protein expression levels of brain-derived neurotrophic factor, triggering receptor expressed on myeloid cells 1, Copine6, and Synaptotagmin1 (Syt-1) decreased in the hippocampus and hypothalamus, whereas the expression of triggering receptor expressed on myeloid cells 2 increased. Interestingly, the fluctuation of temperature and serum concentration of melatonin and corticosterone was significantly different between the groups. Furthermore, protein expression levels of the circadian locomotor output cycles kaput, cryptochrome 2, and period 2 was significantly reduced in the hippocampus of LPS-challenged rats, whereas Bmal1 expression was significantly increased in the hippocampus but decreased in the hypothalamus, where it was co-located with neurons, microglia, and astrocytes. Consistently, apart from the reduced cell viability and increased phagocytic ability, LPS-challenged BV2 cells presented a similar trend with the changed protein expression in the hippocampus of the LPS model rats. However, the pathological changes in BV2 cells induced by LPS were reversed after the suppression of Bmal1. These results indicated that LPS could induce depression-like pathological changes, and the underlying mechanism might be partly associated with the imbalanced expression of Bmal1 and its regulated dysfunction of the circadian rhythm.

Impact of Long-Term Dietary High Fat and Eicosapentaenoic Acid on Behavior and Hypothalamic-Pituitary-Adrenal Axis Activity in Amyloidogenic APPswe/PSEN1dE9 Mice

Introduction: Alzheimer’s disease (AD) alters neurocognitive and emotional function and causes dysregulation of multiple homeostatic processes. The leading AD framework pins amyloid beta plaques and tau tangles as primary drivers of dysfunction. However, many additional variables, including diet, stress, sex, age, and pain tolerance, interact in ways that are not fully understood to impact the onset and progression of AD pathophysiology. We asked: (1) does high-fat diet, compared to low-fat diet, exacerbate AD pathophysiology and behavioral decline? And, (2) can supplementation with eicosapentaenoic (EPA)-enriched fish oil prevent high-fat-diet-induced changes? Methods: Male and female APPswePSdE9 mice, and their non-transgenic littermates, were randomly assigned to a diet condition (low-fat, high-fat, high-fat with EPA) and followed from 2 to 10 months of age. We assessed baseline corticosterone concentration during aging, pain tolerance, cognitive function, stress coping, and corticosterone response to a stressor. Results: Transgenic mice were consistently more active than non-transgenic mice but did not perform worse on either cognitive task, even though we recently reported that these same transgenic mice exhibited metabolic changes and had increased amyloid beta. Mice fed high-fat diet had higher baseline and post-stressor corticosterone, but diet did not impact cognition or pain tolerance. Sex had the biggest influence, as female mice were consistently more active and had higher corticosterone than males. Conclusion: Overall, diet, genotype, and sex did not have consistent impacts on outcomes. We found little support for predicted interactions and correlations, suggesting diet impacts metabolic function and amyloid beta levels, but these outcomes do not translate to changes in behaviors measured here.

Maternally derived avian corticosterone affects offspring genome-wide DNA methylation in a passerine species.

Avian embryos develop in an egg composition which reflects both maternal condition and the recent environment of their mother. In birds, yolk corticosterone (CORT) influences development by impacting pre- and postnatal growth, as well as nestling stress responses and development. One possible mechanism through which maternal CORT may affect offspring development is via changes to offspring DNA methylation. We sought to investigate this, for the first time in birds, by quantifying the impact of manipulations to maternal CORT on offspring DNA methylation. We non-invasively manipulated plasma CORT concentrations of egg-laying female zebra finches (Taeniopygia castanotis) with an acute dose of CORT administered around the time of ovulation and collected their eggs. We then assessed DNA methylation in the resulting embryonic tissue and in their associated vitelline membrane blood vessels, during early development (5 days after lay), using two established methods - liquid chromatography-mass spectrometry (LC-MS) and methylation-sensitive amplification fragment length polymorphism (MS-AFLP). LC-MS analysis showed that global DNA methylation was lower in embryos from CORT-treated mothers, compared to control embryos. In contrast, blood vessel DNA from eggs from CORT-treated mothers showed global methylation increases, compared to control samples. There was a higher proportion of global DNA methylation in the embryonic DNA of second clutches, compared to first clutches. Locus-specific analyses using MS-AFLP did not reveal a treatment effect. Our results indicate that an acute elevation of maternal CORT around ovulation impacts DNA methylation patterns in their offspring. This could provide a mechanistic understanding of how a mother's experience can affect her offspring's phenotype.

Effects of Heat Stress on Breast Muscle Metabolomics and Lipid Metabolism Related Genes in Growing Broilers

With global warming and worsening climatic conditions, heat stress (HS) has become a significant challenge affecting the development of poultry production. In this study, we aimed to determine the effects of HS on breast muscle metabolomics and lipid metabolism-related genes in growing broilers. One hundred twenty 29-day-old Arbor Acres broilers were randomly divided into normal temperature (NT; 21 ± 1 °C) and heat stress (HS; 31 ± 1 °C) groups, with six replicates (ten birds in each replicate) in each group, raised for 14 days in two environment chambers at 60 ± 7% relative humidity. Compared with the broilers in the NT group, the average daily food intake, average daily gain and breast muscle yield in the HS group were significantly lower (p < 0.05). The feed conversion ratio was significantly higher in the HS group (p < 0.05). The concentrations of serum corticosterone, free fatty acids and cholesterol and the percentage of abdominal fat of broilers in the HS group were significantly higher (p < 0.05) than the values of the broilers in the NT group. Untargeted breast muscle metabolome analysis revealed 14 upregulated differential metabolites, including glycerophosphocholine, and 27 downregulated differential metabolites, including taurine, in the HS group compared to the NT group; the HS group also displayed significant effects on six metabolic pathways compared to the NT group (p < 0.05). The mRNA expression levels of peroxisome proliferator-activated receptor gamma coactivator-1-alpha, peroxisome proliferator-activated receptor alpha (PPARα) and ATP-binding cassette transporter A1 in the liver and breast muscles were significantly decreased in the HS group compared with the NT group (p < 0.05). The collective findings reveal that HS can cause disorders in breast muscle lipid metabolism in broilers. The PPARα gene might be the key gene in the mechanism of the lipid metabolism that is induced by HS in breast muscle of broilers. These findings provide novel insights into the effects of HS on chicken growth.

Coated sodium butyrate and vitamin D3 supplementation improve gut health through influencing intestinal immunity, barrier, and microflora in early-stage broilers.

Intestinal development and function are critical to maintaining sustained broiler growth. The present study aimed to evaluate the effects of coated sodium butyrate (CSB) and vitamin D3 (VD3) on the intestinal immunity, barrier, oxidative stress and microflora in early-stage broilers. In total, 192 one-day-old broilers were assigned to a 2 × 2 factorial design including two dietary supplements at two different levels, in which the main effects were VD3 (3000 or 5000 IU kg-1) and CSB (0 or 1 g kg-1). The results showed that CSB supplementation increased ileal goblet cells (GCs) numbers, villus height and decreased crypt depth in broilers. CSB increased ileal proliferating cell nuclear antigen expression and high-level VD3 decreased cluster of differentiation 3 expression. CSB reduced serum d-lactate, endotoxin (ET), adrenocorticotropic hormone, corticosterone and malondialdehyde (MDA) concentrations and increased total antioxidant capacity (T-AOC) level. Meanwhile, high-level VD3 decreased serum ET concentration. Furthermore, CSB increased ileal T-AOC, lysozyme (LYZ) and transforming growth factor (TGF)-β and decreased MDA, whereas high-level VD3 decreased ileal MDA and increased secretory immunoglobulin A. CSB up-regulated ileal claudin1, superoxide dismutase 1, TGF-β and LYZ mRNA expression and down-regulated interleukin-1β mRNA expression. CSB combined with high-level VD3 increased ileal Faecalibaculum abundance. Spearman correlation analysis showed that Faecalibaculum was related to the immune and barrier function. Dietary supplementation with CSB and high-level VD3 improved early gut health in broilers by promoting intestinal development, enhancing antioxidant capacity, strengthening barrier function and enhancing the favorable composition of the gut bacterial flora. © 2024 Society of Chemical Industry.

Research Note: Welfare and stress responses of broiler chickens raised in conventional and animal welfare-certified broiler farms

The present study was conducted to assess the animal welfare status of broiler chickens raised in conventional and welfare-certified farms. One conventional farm (30,000 birds/house, 1,488 m2/house, 2 houses) and one animal welfare-certified farm (32,000 birds/house, 1,920 m2/house, 2 houses) were selected to measure productivity, stress responses, and animal welfare indicators in 3 broiler flocks (2 farms/season, n = 6 flocks/farm type) during summer, autumn, and spring. Upon farm visits, body weight, uniformity, and animal welfare indicators (i.e., fecal and feather corticosterone, footpad dermatitis, hock burn, feather dirtiness, and gait score) were measured at 26 d posthatch. Also, moisture, nitrogen, and pH of litter, light intensity, ammonia concentration, and body surface temperature of head, chest, and legs were measured. There was no difference in body weight and uniformity between farm types. Fecal corticosterone concentrations were higher (P = 0.021) in welfare-certified vs. conventional farm, but no significant difference was found in feather corticosterone. Welfare-certified vs. conventional farm had lower percentages of hock burn (P = 0.018), feather dirtiness scores (P = 0.009), and gait score (P = 0.040), and there was no difference in footpad dermatitis. Nitrogen content in litter samples tended to be higher in conventional vs. welfare-certified farms (P = 0.094), and there was no difference in moisture and pH between farm types. Ammonia concentration within the broiler houses was not different between 2 farms. However, animal welfare farm was found to be brighter than conventional farm (P < 0.001). The body surface temperature of head, chest, and legs was not different between farm types. In conclusion, the welfare-certified farm had higher welfare measures, including lower hock burn, feather dirtiness, and gait score, confirming an overall improvement in welfare indicators. However, the observation on the elevated feather corticosterone noted in welfare vs. conventionally raised chickens warrants further studies.

Adrenalectomy attenuates hyperalgesia but does not regulate muscle wasting in a female rat model of fibromyalgia.

Although it is well established that fibromyalgia (FM) syndrome is characterized by chronic diffuse musculoskeletal hyperalgesia, very little is known about the effect of this pathology on muscle tissue plasticity. Therefore, the present study aimed to characterize the putative alterations in skeletal muscle mass in female rats subjected to a FM model by inducing chronic diffuse hyperalgesia (CDH) through double injections of acidic saline (pH 4.0) into the left gastrocnemius muscle at 5-day intervals. To determine protein turnover, the total proteolysis, proteolytic system activities and protein synthesis were evaluated in oxidative soleus muscles of pH 7.2 (control) and pH 4.0 groups at 7 days after CDH induction. All animals underwent behavioural analyses of mechanical hyperalgesia, strength and motor performance. Our results demonstrated that, in addition to hyperalgesia, rats injected with acidic saline exhibited skeletal muscle loss, as evidenced by a decrease in the soleus fibre cross-sectional area. This muscle loss was associated with increased proteasomal proteolysis and expression of the atrophy-related gene (muscle RING-finger protein-1), as well as reduced protein synthesis and decreased protein kinase B/S6 pathway activity. Although the plasma corticosterone concentration did not differ between the control and pH 4.0 groups, the removal of the adrenal glands attenuated hyperalgesia, but it did not prevent the increase in muscle protein loss in acidic saline-injected animals. The data suggests that the stress-related hypothalamic-pituitary-adrenal axis is involved in the development of hyperalgesia, but is not responsible for muscle atrophy observed in the FM model induced by intramuscular administration of acidic saline. Although the mechanisms involved in the attenuation of hyperalgesia in rats injected with acidic saline and subjected to adrenalectomy still need to be elucidated, the results found in this study suggest that glucocorticoids may not represent an effective therapeutic approach to alleviate FM symptoms.

Research Note: Non-invasive urate sphere corticosterone metabolite as a novel biomarker for heat stress in poultry

Heat stress (HS) poses a critical concern for the global poultry industry. To better understand its impact and mechanism on poultry species, as well as to develop effective HS mitigation options, it is crucial to validate reliable and effective biomarkers of HS. In this study, broiler chickens (96 mixed-sex, 1-day-old) were randomly assigned to 2 environmental conditions: HS at 31°C for 8 h/d versus a thermoneutral condition (TN) at 24°C ± 0.2 throughout the day, from d 21 to d 28. After 7 d of cyclic HS, blood serum samples and the urate sphere (the white portion of the chicken excreta) were collected to measure specific HS biomarkers, including corticosterone, heat shock protein 70 (HSP70), Triiodothyronine (T3), and urate sphere corticosterone metabolite. The results showed that the concentrations of HSP70, T3, and serum corticosterone were not significantly different (P > 0.05) between the heat-stressed and thermoneutral birds in this study. However, heat-stressed birds recorded higher (P < 0.01) concentration (pg/mL) of urate corticosterone metabolite compared to TN birds. Data presented here thus provide preliminary evidence suggesting the use of non-invasive urate sphere corticosterone metabolite as a heat stress biomarker in poultry.

Plasma and Shed-Skin Corticosterone Levels in a Population of Louisiana Pine Snakes (Pituophis ruthveni)

Abstract Measurement of corticosterone in various tissues has been used to investigate the stress response in reptile and amphibian species for decades. The tissue source from which corticosterone is measured reflects different periods of time and chronicity of stress levels in the subject, and different tissue collection methods differ in degree of invasiveness. Studies of corticosterone in keratinized tissues of reptiles, such as shed skin, are limited in number compared to hair and feather glucocorticoid studies in avian and mammalian species, but warrant continued research as they may reflect more different periods of time and chronicity of corticosterone levels than plasma or other tissues, and can be obtained in a minimally invasive manner. In this study, we measured corticosterone concentrations in both plasma and shed skin of Louisiana pine snakes (Pituophis ruthveni) that were all previously diagnosed with subclinical Cryptosporidium serpentis infection. We also tracked stressors experienced by different individuals to identify potential relationships between periods of increased stress and corticosterone levels in plasma and shed skin. There were no significant correlations between individual plasma and shed skin corticosterone levels, or between corticosterone levels in either tissue type and stressors experienced. This is the first study where corticosterone levels were measured in plasma and shed skin of P. ruthveni, and is the first known evaluation of plasma and shed skin corticosterone levels in a snake population previously testing positive for Cryptosporidium serpentis.

Can blubber steroid hormone measurements reveal reproductive state in narwhals?

Abstract Hormone measurements from blubber samples have been used to assess reproduction in cetaceans and are a widely applicable technique, as blubber samples are often collected from necropsied individuals and biopsies are readily collected from live, free-swimming cetaceans. Many studies have assessed reproduction in cetaceans based on blubber hormone concentrations but few have validated their findings with individuals of known reproductive state. The objectives of this study were to use a unique dataset of paired female narwhal (Monodon monoceros) reproductive tracts and blubber samples to: (1) determine narwhal reproductive state based on ovarian analysis; (2) evaluate progesterone, estradiol, testosterone and corticosterone concentrations in paired blubber samples to validate the use of blubber hormone measurements as a technique to assess reproductive state in narwhals; and (3) determine narwhal reproductive rates using reproductive tract and hormone analyses. Female narwhals with complete reproductive tracts or known ages (n = 13) were categorized as: pregnant (fetus or placenta present; n = 5), active (at least one corpus luteum present; n = 2), resting (at least one corpus albicans present; n = 3) or immature (absence of corpora lutea and albicantia or age &amp;lt;8; n = 3), and eight individuals were classified as unknown due to incomplete reproductive tracts. Estradiol, testosterone, and corticosterone concentrations were not useful for assessing reproductive state; however, progesterone concentrations were higher in pregnant narwhals (432.66 ± 182.13 ng/g) than active (1.57 ± 0.42 ng/g), resting (1.52 ± 0.87 ng/g) and immature (1.44 ± 0.71 ng/g) individuals, validating the use of blubber progesterone concentrations in determining pregnancy in narwhals. Using a progesterone threshold for pregnancy, determined in this study, we were able to classify three individuals with incomplete reproductive tracts as pregnant and identify a potential impending pregnancy loss. The results from this study suggest that blubber progesterone concentrations are useful for assessing pregnancy and can help inform reproductive rates of narwhal populations.

Metodologias para indicar estresse causado por jejum em poedeiras comerciais

ABSTRACT: Plasma corticosterone concentration (CORT), heterophil:lymphocyte ratio (H:L), catalase activity (CAT), total glutathione concentration (GSH), and thiobarbituric acid reactive substance levels (TBARS) were evaluated in 48 Hy-Line Brown laying hens, at 79 weeks of age, after being fasted for 10 consecutive days. Blood was collected on days zero, two, four, six, eight, and 10 of fasting, and a completely randomized design was adopted, with eight replicates on each day of collection, with each bird being an experimental unit. The time of maximum stress was determined for each method, using the polynomial regression analysis. The Pearson correlation analysis was also performed to determine whether the methods were interchangeable. CORT and GSH concentrations indicated that the time of maximum stress occurred at 4.3 days of fasting, whereas, the H:L and CAT activity indicated that the time of maximum stress occurred at 10 days of fasting. The malondialdehyde concentration detected by the TBARS method was highest at day zero and lowest at day 5.5 of fasting, but this method was not a reliable measure of stress. The low Pearson correlation coefficients observed among the methods made it impossible to designate only one of the tested methods as a replacement for the others, to measure the stress in laying hens during fasting.

Changes in the Metabolism of Fucose-Containing Biopolymers in Rat Gastrointestinal Tissues under Immobilization Stress

The features of fucoglycoprotein metabolism in blood serum and tissues of gastrointestinal tract of rats in the dynamics of experimental stress on 21, 35, 60, 90 days of observation were considered. In blood serum and in homogenates of liver, stomach and small intestine of immobilized rats multidirectional changes in the level of fucose and fucosidase activity were observed. They are manifested by a decrease in the amount of total fucose in blood serum and liver of rats against the background of low activity of the enzyme degrading fucoglycoproteins. The same changes were detected in the tissues of the gastric and small intestine (except on day 35 of the experiment, when the growth of fucose and fucosidase was visualized), which may indicate a change in metabolism toward anabolism. These changes correlate with an increase in the concentration of corticosterone in the blood serum of the rats.

Physiological and biochemical in vivo study of polyphenols and 20-hydroxyecdisone from quinoa grains effect on resistance to physical exercise in Wistar rats

Increasing the ability of the human body to adapt to physical stress is relevant from the standpoint of using foods for special uses containing functional food ingredients (FFI) with effectiveness proven in vivo. The purpose of this study was to evaluate the effect of FFI from Chenopodium quinoa grains with a high content of polyphenols and phytoecdysteroids on the physical endurance of male Wistar rats. Material and methods. The experiment was carried out during 36 days using 50 weaned male Wistar rats. The animals were randomly divided into 3 groups (n=12): Control, Run and Run-FFI. Rats of the Control and Run groups received a standard semisynthetic diet during the experiment. Rats of the Run-FFI group received a semi-synthetic diet with the addition of FFI in an amount of 0.055±0.003%, containing phytoecdysteroids (50.4±0.6 mg/g) and polyphenols (212.0±2.0 mg/g). During the experiment, the rats were assessed for their neuromotor function (grip strength of front paws), memory, and behavioral reactions in the "Elevated Plus Maze" (EPM), "Conditioned Passive Avoidance Reflex" (CPAR) and "Open Field" (OF) tests. Once a week, animals from the Run and Run-FFI groups were subjected to moderate physical load on a "Treadmill". On the 36th day of the experiment, the animals of these groups were subjected to exhausting physical load. Immediately after running, the animals were placed in metabolic cages to collect daily urine. At the end of the experiment, the content of corticosterone, the activity of catalase, indicators of protein, lipid and mineral metabolism, indexes of the liver functional state and antioxidant defense system parameters were analyzed in the blood serum; the level of prostaglandin E2 and dopamine were determined in daily urine. Results. Physiological tests (CRAR, OF) showed that weekly exercise increased anxiety in laboratory animals. The FFI introduction into the diet led to normalization of the assessed parameters (EPM). As a result of 36-day consumption of FFI against the background of physical loads, a significant decrease by 22% in the main stress marker, corticosterone, was revealed in the blood of rats, as well as significant increase by 23% in the stress inhibitor - prostaglandin E2 urinary excretion, compared with animals of the Run group to the level not differed from the indicators of the control animals. There were no differences in endurance performance between the Run and Run-FFI groups on the results of the exhaustive exercise. Consumption of FFI prevented the formation of excess ammonia, significantly reducing the level of urea in the blood and normalizing its excretion to control levels in the urine, which was increased in the Run group by 19%. Conclusion. The results obtained demonstrated the adaptogenic properties of the developed FFI in response to stress caused by weekly moderate and acute exhaustive physical activity. The obtained data on the biological effect of the developed FPI on the adaptive potential of laboratory animals will serve as an experimental basis for its inclusion in the composition of specialized foods.

ВЛИЯНИЕ ЭКСПЕРИМЕНТАЛЬНОЙ ДЕПРЕССИИ НА ФУНКЦИОНАЛЬНОЕ СОСТОЯНИЕ ГИПОТАЛАМО-ГИПОФИЗАРНО-НАДПОЧЕЧНИКОВОЙ СИСТЕМЫ

Objective: To study the effect of modelled depression not associated with stress on the hypothalamic-pituitary-adrenal system (HPAS) in mice. Methods: The experiment was conducted on the twenty-four C57BL/6 mice weighing 20-25 g, divided into two groups: an experimental one, involving animals with reserpine-induced depression, and a control one, the animals of which were administered normal saline instead of reserpine solution. At the end of the experiment, behavioral tests were performed (open field, sucrose preference, forced swimming), and the corticosterone concentration in blood was measured using ELISA. Image analysis of histological changes in the adrenal gland and thymus was performed. All results were statistically processed using SPSS 27.0.1 software, with p&lt;0.05 indicating the significance of differences. Results: Animals of the experimental group showed a significantly higher level of corticosterone in the blood (p&lt;0.01), significant changes in behavior in the open field test (distance traveled, rearing, frequency of urination and defecation, p&lt;0.01), reduced sucrose preference (p&lt;0.01) and shortened duration of the active phase in the forced swimming test (p&lt;0.01) than the animals of the control group. Besides, in the mice of the experimental group, a significant increase in the volume density of the zona fasciculata of the adrenal cortex was found (p&lt;0.05), as well as the area of its spongiocytes and their nuclei (p&lt;0.05). In the thymus of the experimental animals, a significant decrease in the cortex-medulla ratio was noted (p&lt;0.05); and an increase in the volume density of tingible body macrophages (p&lt;0.05) compared to the control group of mice. Conclusion: Modelled depression, not associated with stress, the depth of which was assessed by behavioral tests, caused activation of the HPAS, manifested by increased corticosterone levels, hyperplasia of the zona fasciculata of the adrenal cortex, hypertrophy of its spongiocytes and their nuclei, as well as changes in the thymus, indicating associated immunosuppression. Thus, the study showed that, along with the well-known phenomenon of the development of depression against the background of chronic stress-associated activation of HPAS, there is an inverse mechanism leading to activation of the HPAS during the development of depression not associated with stress, which must be taken into account when developing the new strategies of treating depression. Keywords: Depression, hypothalamic-pituitary-adrenal system, corticosterone, immune system, mice.

Thoughtful or distant farmer: Exploring the influence of human-animal relationships on rabbit stress, behaviour, and emotional responses in two distinct living environments

Abstract Both the nature of the human-animal relationship (HAR) and housing conditions significantly impact the welfare of farmed animals. To evaluate the influence of HAR on the behaviour, emotions and stress of rabbits (Oryctolagus cuniculus) in two distinct outdoor living environments, we allocated 144 young rabbits to four groups (CPX-H, CPX-N, SPL-H, SPL-N) differing in the living environments (CPX for complex, and SPL for simple). The treatment by human (H) involved daily provision of additional food resources and stroking (thoughtful farmer). It commenced at 49 days of age and lasted for 16 days. N groups did not receive the treatment (distant farmer). The rabbits were observed between 48 and 73 days of age. Their behavioural responses to human presence were evaluated at 48 and 68 days using Qualitative Behaviour Assessment (QBA) and scan sampling. A set of tests was conducted at 68 days of age to assess their reactions to a novel object and human presence. Stress levels were measured by analysing corticosterone concentrations in their hair. Rabbits in the SPL environment spent significantly more time near the novel object than those in the CPX environment (24.7 vs 17.2%). Additionally, rabbits in the H treatment group spent more time near the human than those in the N treatment group (28.2 vs 17.1%) and accepted more strokes (90.2 vs 45.9%). Following the HAR treatment, rabbits in the H group were significantly more likely to be described as ‘Affectionate/Interested’ than those in the N treatment. Rabbits in the N treatment were described as ‘Indifferent’ significantly more in the SPL environment. However, there were no significant differences in hair corticosterone concentrations between the groups. These findings indicate that rabbits’ responses are influenced by both their living environment and the quality of their relationship with humans. Encouraging positive interactions with animals may enhance their welfare and facilitate daily care from farmers.

Effects of Corticosterone on Beta-Amyloid-Induced Cell Death in SH-SY5Y Cells.

Alzheimer's disease (AD) is a neurodegenerative disease characterized by neuronal cell death and memory impairment. Corticosterone (CORT) is a glucocorticoid hormone produced by the hypothalamic-pituitary-adrenal axis in response to a stressful condition. Excessive stress and high CORT levels are known to cause neurotoxicity and aggravate various diseases, whereas mild stress and low CORT levels exert beneficial actions under pathophysiological conditions. However, the effects of mild stress on AD have not been clearly elucidated yet. In this study, the effects of low (3 and 30 nM) CORT concentration on Aβ25-35-induced neurotoxicity in SH-SY5Y cells and underlying molecular mechanisms have been investigated. Cytotoxicity caused by Aβ25-35 was significantly inhibited by the low concentration of CORT treatment in the cells. Furthermore, CORT pretreatment significantly reduced Aβ25-35-mediated pro-apoptotic signals, such as increased Bim/Bcl-2 ratio and caspase-3 cleavage. Moreover, low concentration of CORT treatment inhibited the Aβ25-35-induced cyclooxygenase-2 and pro-inflammatory cytokine expressions, including tumor necrosis factor-α and interleukin-1β. Aβ25-35 resulted in intracellular accumulation of reactive oxygen species and lipid peroxidation, which were effectively reduced by the low CORT concentration. As a molecular mechanism, low CORT concentration activated the nuclear factor-erythroid 2-related factor 2, a redox-sensitive transcription factor mediating cellular defense and upregulating the expression of antioxidant enzymes, such as NAD(P)H:quinone oxidoreductase, glutamylcysteine synthetase, and manganese superoxide dismutase. These findings suggest that low CORT concentration exerts protective actions against Aβ25-35-induced neurotoxicity and might be used to treat and/or prevent AD.

Exploring the effects of noise pollution on physiology and ptilochronology of birds.

An ex-situ study was carried out to determine the impact of noise on physiology and ptilochronology of non-breeding male domesticated quail birds. During 60-days long trial, male quail birds, aged 5-weeks, weighing (c.100gm) were used. Out of 72 experimental birds, 18 birds were assigned to the Control Group (G1) while remaining 54 birds were divided equally into 3 treatment groups: Road Traffic noise (G2), Military activity noise (G3) and Human Activities noise (G4). Birds were housed in standard-sized separate cages (20 ×45 × 20 cm), every bird was kept apart in separate cage in open laboratory under maintained environmental conditions. Millet seeds and water were provided to all the experimental birds ad libitum. Noise originated from several sources of recorded high-intensity music (1125 Hz/ 90 dB), was administered for 5-6 hours per day. Observations were recorded in the morning and afternoon. The experiment was conducted during the non-breeding season from August to October in triplicate. Blood sampling was done after 60 days. According to the current study, noise stress significantly (p<0.05) increased the concentrations of creatinine, aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), bilirubin, uric acid, cholesterol, triglycerides, total protein, and glucose while a decline in the levels of albumin was seen in treatment birds of G3. While in terms of hematology, total white blood cells count (TWBC), total red blood cells count (TRBC), mean cell volume (MCV) & packed cell volume (PCV) concentrations were raised in blood of treatment birds of G3. In terms of hormones, noise stress significantly (p<0.05) increased the serum concentrations of Corticosterone in G3 while a significant (p<0.05) decline was observed in the concentrations of luteinizing hormone (LH), thyroid stimulating hormone (TSH), and follicle stimulating hormone (FSH) in the same group. Moreover, fault bar formation in G3 was more prominent than others. Noise stress can significantly affect serology, hematology, hormonal physiology and ptilochronology in quail birds.

Post-natal antibiotic exposure in mother rat (F0) induces anxiety like behavior in adult rat offspring (F1) by activating HPA axis and down-regulating the Nr3c1 gene.

Early postnatal administration of antibiotics has been linked to lasting effects on brain development and behavior. Research conducted on animals that are free from germs has demonstrated that the impact of microbiome colonization on the regulation of the hypothalamic-pituitary-adrenal (HPA) axis and neuroendocrine pathways is substantial, which play a crucial role in stress management. Nevertheless, it is still uncertain if the exposure to antibiotics in rat dams (F0-generation) before weaning is associated with neurobehavioral changes in rat offspring (F1-generation) during adulthood. In order to investigate the effects, we perturbed the intestinal microbiota of rat dams (F0 generation) by administering cefixime (CEF), an antibiotic commonly used for obstetric purposes, at clinically relevant doses (1 mg/kg, 2.5 mg/kg or 5 mg/kg). Anxiety-like behaviors in adult offspring was evaluated through the utilization of elevated plus maze (EPM) and open field paradigm (OFP) following a six-week interval from birth (PND42). Subsequent to behavioral assessments, the rats were euthanized, and their brains and blood was collected for biochemical analysis. Plasma corticosterone concentration was used to assess HPA activity, whereas the quantitative real-time polymerase chain reaction (PCR) was employed to determine the transcription levels of the glucocorticoid receptor (GR) Nr3c1. The offspring of F1 that were administered antibiotics before being weaned spent less time in the EPM open arm. The alterations were accompanied by increased levels of corticosterone in the bloodstream. The gene expression study revealed a decrease in the levels of mRNA transcription of Nr3c1. This research emphasizes the possible long-term effects of antibiotic exposure before weaning on the development of anxiety in offspring upon adulthood.

Neurobiological traces of grief: Examining the impact of offspring loss after birth on rat mothers’ brain and stress-coping behavior in the first week postpartum

The bond between a mother and her infant is one of the strongest social bonds found in mammals. Consequently, the loss of an infant has immense psychological and physiological effects on the caregiver. Despite the significance of this bereavement, only a few studies have investigated the neurobiological impact of offspring loss in mothers. In an approach to fill this gap, we studied the effects of losing all pups the day after giving birth on rat mothers' brain and stress-coping behavior. Specifically, dams experienced 1-, 3-, or 6-days of total offspring loss. We analyzed the neuronal activity and oxytocin receptor (OXT-R) binding in the brain limbic and maternal network regions, as well as the stress response and stress-coping strategies. Following 1 day of loss, the mothers' neuronal activity increased in the limbic system resulting in a positive correlation between the prelimbic cortex and basolateral amygdala, while OXT-R binding was decreased in the central amygdala following up to 3 days of loss. At all three timepoints, plasma corticosterone concentrations did not differ either under basal conditions or following stressor exposure. Remarkably, following 6 days of offspring loss, the mothers showed a significant increase in passive stress-coping behavior, marking the first evidence of offspring loss affecting rat mothers' stress-coping behavior. Our results emphasize the significant impact of offspring loss on the mothers’ neuronal activity and brain oxytocin system thereby providing novel insight into the short-term neurobiological traces of grief and paving new avenues for future research in this field.

Robust Responses of Female Caribou to Changes in Food Supply.

AbstractUngulates can respond to changes in food supply by altering foraging behavior, digestive function, and metabolism. A multifaceted response to an environmental change is considered robust. Short seasons of plant growth make herbivores sensitive to changes in food supply because maintenance and production must be accomplished in less time with fewer options in a more fragile response. Caribou live at high latitudes where short summers constrain their response to changes in food supply. We measured the ability of female caribou to resist and tolerate changes in the quality and quantity of their food supply during winter and summer. Caribou resisted changes in food abundance and quality by changing food intake and physical activity with changes in daily temperature within each season. Peak food intake rose by 134% from winter pregnancy to summer lactation (98 vs. 229 g kg-0.75 d-1), as digestible requirements to maintain the body increased by 85% for energy (1,164 vs. 2,155 kJ kg-0.75 d-1) and by 266% for N (0.79 vs. 2.89 g N kg-0.75 d-1). Caribou required a diet with a digestible content of 12 kJ g-1 and 0.8% N in pregnancy, 18 kJ g-1 and 1.9% N in early lactation, and 11 kJ g-1 and 1.2% N in late lactation, which corresponds with the phenology of the wild diet. Female caribou tolerated restriction of ad lib. food intake to 58% of their energy requirement (680 vs. 1,164 kJ kg-0.75 d-1) during winter pregnancy and to 84% of their energy requirement (1,814 vs. 2,155 kJ kg-0.75 d-1) during summer lactation without a change in stress level, as indicated by fecal corticosterone concentration. Conversely, caribou can respond to increased availability of food with a spare capacity to process digestible energy and N at 123% (2,642 vs. 2,155 kJ kg-0.75 d-1) and 145% (4.20 vs. 2.89 g N kg-0.75 d-1) of those respective requirements during lactation. Robust responses to changes in food supply allow caribou to sustain reproduction, which would buffer demographic response. However, herds may decline when thresholds of behavioral resistance and physiological tolerance are frequently exceeded. Therefore, the challenge for managing declining populations of caribou and other robust species is to identify declines in robustness before their response becomes fragile.