Higher Corticosterone Levels Research Articles

Growth Differentiation Factor 15 during pregnancy and postpartum as captured in blood, cerebrospinal fluid and placenta: A cohort study on associations with maternal mental health

IntroductionGrowth Differentiation Factor 15 (GDF15) increases substantially during pregnancy and is primarily produced by the placenta. Elevated levels of GDF15 have been associated with mental health problems in non-perinatal populations, higher corticosterone levels, and decreased estrogen receptor activity. However, the role of GDF15 in mental health during the perinatal transition remains unknown. This longitudinal study is the first to evaluate pregnancy levels of GDF15 in cerebrospinal fluid (cGDF15), plasma (pGDF15) and placenta GDF15 mRNA, along with mapping plasma GDF15 (pGDF15) level changes from late pregnancy to early postpartum. Moreover, we aimed to evaluate the association between pregnancy cGDF15 levels and cortisol early postpartum, evaluate the association between pregnancy cGDF15 levels and mental health in pregnancy and postpartum, and evaluate the association between pGDF15 and estrogens and high-sensitivity C-reactive protein (CRP). MethodsWe included data from 95 women scheduled for a planned cesarean section and obtained cerebrospinal fluid (CSF) and plasma levels of GDF15. We quantified GDF15 mRNA levels in placenta biopsies. Estrogens, high-sensitivity CRP, and mental health measures were further collected on the day or one day before the cesarean section. At five weeks postpartum, mental health measures and saliva samples for cortisol analyses were collected. Correlation analyses for GDF15 in CSF, plasma, and placenta mRNA were performed, along with association analyses for pregnancy cGDF15, Cortisol Awakening Response, and mental health outcomes. ResultsWe demonstrated a strong correlation between cGDF15 and pGDF15 (r=0.52; p<0.001) and found that both cGDF15 and pGDF15 correlated with placenta GDF15 mRNA*placental weight (r=0.62, p<0.001 and r=0.44, p=0.008, respectively). During late pregnancy, both estradiol (E2) and estriol (E3) were significantly associated with pGDF15 levels (E2: p=0.002; E3: p(corrected)<0.001). Finally, we found that cGDF15 levels were not associated with self-reported mental well-being or the Cortisol Awakening Response or absolute cortisol at awakening postpartum. ConclusionThis novel study points to the unique hormonal landscape during the perinatal transition and the specific role of GDF15 in pregnancy, which appears uncoupled with perinatal mental health and cortisol outcomes. Our data also strongly imply that the overall amount of circulating GDF15 in late pregnancy is closely related to placenta size.

Detrimental effect of prenatal progesterone exposure on anxiety and depressive-like responses in adult male and female rat offspring: role of plasma, hippocampal corticosterone and hippocampal progesterone receptors

In clinical practice, the use of exogenous progesterone (Pro) is often required in assisted reproduction programs due to reduced levels of the hormone and the risk of miscarriage. Exposure to the hormone reduces anxiety in rodents, but the long-term effects of prenatal exposure in adult offspring are unknown. Therefore, the present study was designed to investigate the effect of prenatal Pro treatment on anxiety- and depression-like behavior and the effect on plasma, hippocampal corticosterone (CORT) and hippocampal progesterone receptor (PR) in young adult male and female rat offspring. The behavioral responses of offspring of both sexes were tested in the open field, and the elevated plus maze tests, and for depressive-like behavior in the sucrose preference test, the forced swimming test and the splash test. CORT levels and PR expression were measured by ELISA. The results indicate that prenatal Pro exposure at low and high doses (10 and 50 mg/kg, s.c. during G0-G10) induces anxiogenic and depressive-like effects compared to vehicle-treated controls, which are associated with high plasma and hippocampal CORT levels and upregulated hippocampal PR in male and female adult offspring. Our results demonstrate that prenatal Pro exposure has detrimental effects on the emotional status of male and female adult offspring, which may be associated with long-term changes in hormonal homeostasis.

Pineapple (Ananas comosus) Ameliorates Depressant-like Behaviors in Rats Induced by Lipopolysaccharide

Background: Lipopolysaccharide (LPS) injection can lead to depression and mood disorders by reducing tryptophan availability through increased activity of the enzyme indoleamine 2,3-dioxygenase. Tryptophan, sourced from fruits such as pineapple (Ananas cosmosus), is vital for the body, especially the serotonergic system. Aim: This study aims to assess how pineapple pulp (PP) counters LPS-induced depressive behaviors in male Wistar rats. Methods: The experiment involved force-feeding PP for 28 days before LPS injection (0.5 mg/kg intraperitoneal [i.p.]) in 30 male Wistar rats, divided into five groups. Groups I (normal) and II (LPS control) received 15 ml aquadest/kg/day. Test Groups III, IV, and V were given varied doses of PP; low dose (3.75 ml/kg/day), medium dose (7.5 ml/kg/day), and high dose (15 ml/kg/day). At the study’s end, rats underwent the open field test (OFT) and the tail suspension test (TST). In addition, blood and brain samples were analyzed for neuroendocrine markers related to depression. Results: LPS triggers depressive symptoms, as evidenced by increased immobility time in the TST and altered behaviors indicative of anxiety in the OFT, especially in groups not receiving PP. This is followed by decreased serotonin levels in both plasma and brain when compared to groups given PP. In addition, higher corticosterone levels were observed in the LPS group than in the PP-treated group. Administering PP at 7.5 ml/kg/day for 28 days can alleviate the depressive effects induced by LPS injection. Conclusion: PP may have antidepressant properties, potentially by mitigating behaviors leading to depressive symptoms.

Experimentally elevated corticosterone increases song output and complexity in common mynas.

Vocalization is an important communication tool that can reflect many aspects of an individual's internal and external condition. This is especially true for birds. Previous research has shown that bird calls and songs change in response to a variety of potential stressors, although the extent and direction of the changes depend on the nature of the stressor and the environment. Circulating glucocorticoids, such as corticosterone, often increase in response to stressors and mediate some of the observed changes via alterations of the individual's physiological state. Acute elevations of corticosterone often occur as a physiological response to short-term stressors; however, the effects of this elevation on adult vocalizations have not been well documented. Here, we experimentally elevated corticosterone at two different levels using a noninvasive method and examined the effects on the vocal communication of male and female adult common mynas (Acridotheres tristis). Corticosterone elevation temporarily increased song output and some measures of song complexity, while call output decreased. These effects were dosage dependent (higher corticosterone levels had a stronger effect), most evident 40 min after ingestion, and some vocal changes were sex-specific. Future studies should investigate whether the changes in vocal performance due to elevated glucocorticoids have consequences for the birds' behavior, reproductive success, and survival.

The role of melatonin deficiency induced by pinealectomy on motor activity and anxiety responses in young adult, middle-aged and old rats.

Aging affects anxiety levels in rats while the pineal gland, via its hormone melatonin, could modulate their inherited life "clock." The present study aimed to explore the impact of plasma melatonin deficiency on anxiety responses and the possible involvement of the hypothalamic-pituitary-adrenocortical (HPA) axis and heat shock proteins (Hsp) 70 and 90 in the frontal cortex (FC) and the hippocampus in young adult, middle-aged and elderly rats with pinealectomy. Melatonin deficiency induced at different life stages did not affect the lifespan of rats. Pinealectomy abolished the circadian rhythm of motor activity, measured for 48h in the actimeter, in young adult but not in middle-aged rats. Pinealectomy reduced the motor activity of the young adult rats during the dark phase and impaired the diurnal activity variations of old rats. The same generations (3- and 18month-old rats with pinealectomy) had lower anxiety levels than the matched sham groups, measured in three tests: elevated-plus maze, light-dark test, and novelty-suppressed feeding test. While the activity of the HPA axis remained intact in young adult and middle-aged rats with melatonin deficiency, a high baseline corticosterone level and blunted stress-induced mechanism of its release were detected in the oldest rats. Age-associated reduced Hsp 70 and 90 levels in the FC but not in the hippocampus were detected. Pinealectomy diminished the expression of Hsp 70 in the FC of middle-aged rats compared to the matched sham rats. Our results suggest that while melatonin hormonal dysfunction impaired the motor activity in the actimeter and emotional behavior in young adult and elderly rats, the underlying pathogenic mechanism in these generations might be different and needs further verification.

Restricted effects of androgens on glucocorticoid signaling in the mouse prefrontal cortex and midbrain.

Glucocorticoids are key executors of the physiological response to stress. Previous studies in mice showed that the androgen receptor (AR) influenced the transcriptional outcome of glucocorticoid treatment in white and brown adipocytes and in the liver. In the brain, we observed that chronic hypercorticism induced changes in gene expression that tended to be more pronounced in male mice. In the present study, we investigated if glucocorticoid signaling in the brain could be modulated by androgen. After chronic treatment with corticosterone, dihydrotestosterone, a combination of both, and corticosterone in combination with the AR antagonist enzalutamide, we compared the expression of glucocorticoid receptor (NR3C1, also abbreviated GR) target genes in brain regions where AR and GR are co-expressed, namely: prefrontal cortex, hypothalamus, hippocampus, ventral tegmental area and substantia nigra. We observed that androgen affected glucocorticoid signaling only in the prefrontal cortex and the substantia nigra. Dihydrotestosterone and corticosterone independently and inversely regulated expression of Sgk1 and Tsc22d3 in prefrontal cortex. AR antagonism with enzalutamide attenuated corticosterone-induced expression of Fkbp5 in the prefrontal cortex and of Fkbp5 and Sgk1 in the substantia nigra. Additionally, in the substantia nigra, AR antagonism increased expression of Th and Slc18a1, two genes coding for key components of the dopaminergic system. Our data indicate that androgen influence over glucocorticoid stimulation in the brain is not a dominant phenomenon in the context of high corticosterone levels, but can occur in the prefrontal cortex and substantia nigra.

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.

Effect of Bee Bread on Corticosterone Level in Rat Dams Exposed to Gestational Heat Stress.

Environmental temperature rises are powerful stimuli that can alter both the sympathetic nervous system and the hypothalamic-pituitary-adrenocortical axis (HPA). Heat stress has been shown to harm pregnancy outcomes such as causing spontaneous abortion, low birth weight, growth retardation and stillbirth. Supplementation of bee bread in pregnant rats under heat stress exposure has been shown to improve the pregnancy outcomes. However, whether supplementation of bee bread during heat stress exposure may also reduce the level of the stress hormone, corticosterone has yet been reported. Therefore, this study aims to determine the effect of bee bread on corticosterone level, progesterone level, oestradiol level and zonation of the adrenal cortex of pregnant rats under heat stress exposure. Pregnant rats were randomly categorised into four groups (n = 6): Control (C: standard feeding), Treatment 1 (T1: 0.5 g bee bread/kg body weight/day), Treatment 2 (T2: standard feeding with heat exposure), and Treatment 3 (T3: 0.5 g bee bread/kg body weight/day with heat exposure). Bee bread (0.5 g/kg body weight/day) was force-fed to pregnant rats through oral gavage beginning on day 0 of pregnancy and continuing until delivery. Heat stress was generated experimentally by putting both T2 and T3 rats in an egg incubator for 45 min daily at a temperature of 43°C till delivery. On a postnatal Day 21, dams were euthanised to assess serum corticosterone, progesterone, oestradiol levels and adrenal gland histology. Rats in the T2 group had a significantly (P < 0.05) increase in the zona fasciculata thickness (94.95 ± 1.55 μm) and higher corticosterone levels (49.57 ± 1.57 ng/mL) compared with control. However, supplementation of bee bread during heat stress was able to show an improvement in adrenal zona fasciculata thickness by decreasing to 79.89 ± 3.08 μm and corticosterone level reduced to 35.31 ± 1.73 ng/mL significantly (P < 0.05). Therefore, these findings may imply that bee bread is effective as a neutralizer in lowering the production of stress hormone.

Stress-induced Neuroinflammation of the Spinal Cord is Restrained by Cort113176 (Dazucorilant), A Specific Glucocorticoid Receptor Modulator.

Glucocorticoids exert antiinflammatory, antiproliferative and immunosupressive effects. Paradoxically they may also enhance inflammation particularly in the nervous system, as shown in Cushing´ syndrome and neurodegenerative disorders of humans and models of human diseases. ."The Wobbler mouse model of amyotrophic lateral sclerosis shows hypercorticoidism and neuroinflammation which subsided by treatment with the glucocorticoid receptor (GR) modulator Dazucorilant (CORT113176). This effect suggests that GR mediates the chronic glucocorticoid unwanted effects. We now tested this hypothesis using a chronic stress model resembling the condition of the Wobbler mouse Male NFR/NFR mice remained as controls or were subjected to a restraining / rotation stress protocol for 3 weeks, with a group of stressed mice receiving CORT113176 also for 3 weeks. We determined the mRNAS or reactive protein for the proinflamatory factors HMGB1, TLR4, NFkB, TNFα, markers of astrogliosis (GFAP, SOX9 and acquaporin 4), of microgliosis (Iba, CD11b, P2RY12 purinergic receptor) as well as serum IL1β and corticosterone. We showed that chronic stress produced high levels of serum corticosterone and IL1β, decreased body and spleen weight, produced microgliosis and astrogliosis and increased proinflammatory mediators. In stressed mice, modulation of the GR with CORT113176 reduced Iba + microgliosis, CD11b and P2RY12 mRNAs, immunoreactive HMGB1 + cells, GFAP + astrogliosis, SOX9 and acquaporin expression and TLR4 and NFkB mRNAs vs. stress-only mice. The effects of CORT113176 indicate that glucocorticoids are probably involved in neuroinflammation. Thus, modulation of the GR would become useful to dampen the inflammatory component of neurodegenerative disorders.

Metabolic dysfunctions following chronic oral corticosterone are modified by adolescence and sex in mice

Adolescence is a period of development in which shifts in responses to glucocorticoids is well-documented. Obesity and metabolic syndrome are substantial health issues whose rates continue to rise in both adult and adolescent populations. Though many interacting factors contribute to these dysfunctions, how these shifts in glucocorticoid responses may be related remain unknown. Using a model of oral corticosterone (CORT) exposure in male and female mice, we demonstrate differential responses during adolescence (30–58 days of age) or adulthood (70–98 day of age) in endpoints relevant to metabolic function. Our data indicate that CORT resulted in significant weight gain in adult- and adolescent-exposed females and adult-exposed males, but not adolescent-exposed males. Despite this difference, all animals treated with high levels of CORT showed significant increases in white adipose tissue, indicating a dissociation between weight gain and adiposity in adolescent-treated males. Similarly, all experimental groups showed significant increases in plasma insulin, leptin, and triglyceride levels, further suggesting potential disconnects between overt weight gain, and underlying metabolic dysregulation. Finally, we found age- and dose-dependent changes in the expression of hepatic genes important in glucocorticoid receptor and lipid regulation, which showed different patterns in males and females. Thus, altered transcriptional pathways in the liver might be contributing differentially to the similar metabolic phenotype observed among these experimental groups. We also show that despite little CORT-induced changes in the hypothalamic levels of orexin-A and NPY, we found that food and fluid intake were elevated in adolescent-treated males and females. These data indicate chronic exposure to elevated glucocorticoid levels results in metabolic dysfunction in both males and females, which can be further modulated by developmental stage.

Hair glucocorticoids are not a historical marker of stress – Exploring the time-scale of corticosterone incorporation into hairs in a rat model

Hair glucocorticoids are increasingly popular biomarkers, used across numerous research fields, and studied species, as a measure of stress. Although they are suggested to be a proxy of the average HPA axis activity spanning a period of weeks or months into the past, this theory has never been tested.In the present study, adrenalectomized rats with no endogenous (adrenal) glucocorticoid production were used to study how circulating glucocorticoid levels would be reflected in the glucocorticoid levels found in hair samples. By dosing the animals daily with high levels of corticosterone for seven days, while sampling hairs before, during, and after treatments, a timeline for glucocorticoid uptake into hairs was constructed. This kinetic profile was compared to two hypothetical models, and the theory that hair glucocorticoids are a record of historical stress had to be rejected.Corticosterone concentrations in hairs were found to increase within three hours of the first injection, the highest concentrations were found on the seventh day of treatments, and the decrease in concentrations post-treatment suggests rapid elimination. We speculate that hair glucocorticoid levels can only be used to characterize a stress-response for a few days following a postulated stressor.An updated model, where glucocorticoids diffuse into, along, and out of hairs needs to be adopted to reconcile the experimentally obtained data. The inescapable consequence of this updated model is that hair glucocorticoids become a marker of – and can only be used to study – recent, or ongoing, stress, as opposed to historical events, weeks or months in the past.

Effects of intra-hippocampal corticosterone and sleep on consolidation of memories of aversive experience in rats

Formation and consolidation of memories for highly stressful (traumatic) events is a complex process that involves interplay between multiple memory systems and has implications for etiology and treatment of stress- and trauma-related disorders. Here we study effects of sleep/wake states and high intra-hippocampal corticosterone on consolidation of aversive contextual memories, as well as consolidation of association between auditory unpaired phasic background cues and fear response in rats. Animals were implanted with EEG and EMG electrodes for sleep assessment and cannulas for intra-hippocampal corticosterone application. They were familiarized to a “safe box” and then trained in a fear conditioning paradigm in a distinct “shock box” with a prominent unpaired phasic background auditory cue. Immediately after conditioning, animals received bilateral intra-hippocampal saline (1 μl) or corticosterone (10 ng in 1 μl) injection and were either allowed to sleep or were kept awake for a following two-hour consolidation period. Memory tests 24 h later revealed that the saline-injected animals that slept during consolidation had significantly stronger fear responses in the shock box compared to the safe box as well as increased fear response in response to the auditory cue. Lack of sleep during the consolidation period in saline injected animals led to generalization of the fear response to the safe context, while association between auditory cue and fear response was preserved. High intra-hippocampal corticosterone levels during memory consolidation led to generalization of fear response to the safe context, regardless of sleep/wake state, while enhancement of response to auditory cue was not observed. Our results show how manipulation of conditions during consolidation can lead to greatly variable memories for an aversive episode with distinct behavioral outcomes. Observed overgeneralization of fear to safe context and altered fear response to background phasic cue has implications for understanding etiology of pathological memory alternations in stress-related conditions e.g., in posttraumatic stress disorder in humans.

Lungworm parasite intensity and its association with the endocrine and immune systems and energy reserves in male cane toads

Host-parasite interactions can be harmful or harmless depending on the fitness and stress levels of the organisms. Interactions between the endocrine system, the immune system and energy expenditure are critical in the maintenance of homeostasis during stressful periods in vertebrates. We examined whether lungworm loads (Rhabdias spp.) of male cane toad (Rhinella marina) sampled during the wet season from three different populations, are associated with hormone levels, immune competence, and metabolic status. We found evidence of direct and strong associations between parasite burdens and variables related to hormonal levels, metabolic status and immune competence. We also found that interrelationships among independent variables can change the strength of the association with lungworm loads. These findings suggest that high levels of corticosterone affect immune competence against parasites, both directly and by inducing changes in the metabolic status of the animals. Additionally, high testosterone levels during the reproductive season, influenced variables related to metabolic status, which will also lead to higher parasite loads. Overall, we conclude that the endocrine system and metabolic status in male cane toads are critical to the immune competence against parasites during the reproductive season.

Bivalves Transmissible Neoplasia: Biochemical Aspects of Contagious Cancer in a Clam Macoma Balthica.

Occurring in marine invertebrates infectious haemic neoplasia (bivalves transmissible neoplasia, BTN) arises from genome instabilities leading to multilevel malfunctions and unregulated cell division of presumably haemocyte precursors. As its biochemical characterisation remains unknown, we here present the first data describing selected aspects of the physiology and biochemistry of the disease a in model clam Macoma balthica. We chose free amino acids (FAA) composition, mitochondrial respiration and enzymatic activity, oxidative stress enzymes activities and corticosteroids profile as markers of this contagious cancer. Selected markers were measured in neoplastic and healthy clams and two tissue types, haemolymph and solid tissue. FAA composition was assessed in the haemolymph samples using high performance liquid chromatography-mass spectrometry (LC/MS). Mitochondrial respiration analysis was performed on haemocytes using oxygen electrodes integrated system Seahorse XFp. Mitochondrial enzymes activities were measured using spectrophotometry (cytochrome oxidase, COX) and commercial kit (succinate dehydrogenase, SDH). Total Antioxidant Capacity (TAC), Acetylocholinesterase (AChE), Protein Carbonyl Content (CBO) and Malondialdehyde (MDA) levels were measured in the solid tissue using analytical kits, and glutathione (GSH) was measured spectrophotometrically. Corticosteroids profile, measured in the solid tissue, was obtained with Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (HPLC-ESI-MS/MS) technique. In both clam groups nine FAAs were detected with Asp, Glu, Pro, Ser constituting over 90% of total FAA content. Significantly higher Gln level was detected in BTN positive clams. In neoplastic clams, an impairment of mitochondrial metabolism was observed as a decrease in mitochondrial oxygen consumption and lower cytochrome c oxidase activity. In the neoplastic clams significantly higher concentration of low molecular weight antioxidants was found. Finally, we report high level of corticosterone and lower levels of dehydrocorticosterone, cortisol and cortisone in healthy clams and elevated cortisol level in BTN individuals. Neoplastic clams are characterized by altered mitochondrial metabolism, with a potential key role of glutamine (Gln) in cancer cells energy production. Despite low aerobic respiration, BTN cells have efficient antioxidative response to elevated concentration of ROS. Elevated cortisol level in BTN-positive clams may indicate an important role of this corticosteroid in cancer biochemistry. Thus, we here provide the first results of selected physiological and biochemical aspects of BTN, making an important step in studying cancer epidemiology in wildlife.

Non-native grazers affect physiological and demographic responses of greater sage-grouse.

Non‐native ungulate grazing has negatively impacted native species across the globe, leading to massive loss of biodiversity and ecosystem services. Despite their pervasiveness, interactions between non‐native grazers and native species are not fully understood. We often observe declines in demography or survival of these native species, but lack understanding about the mechanisms underlying these declines. Physiological stress represents one mechanism of (mal)adaptation, but data are sparse. We investigated glucocorticoid levels in a native avian herbivore exposed to different intensities of non‐native grazing in the cold desert Great Basin ecosystem, USA. We measured corticosterone, a glucocorticoid in feathers for a large sample (n = 280) of female greater sage‐grouse (Centrocercus urophasianus) from three study areas in Northern Nevada and Southern Oregon with different grazing regimes of livestock and feral horses. We found that greater feral horse density was associated with higher corticosterone levels, and this effect was exacerbated by drought conditions. Livestock grazing produced similar results; however, there was more model uncertainty about the livestock effect. Subsequent nesting success was lower with increased feather corticosterone, but corticosterone levels were not predictive of other vital rates. Our results indicate a physiological response by sage‐grouse to grazing pressure from non‐native grazers. We found substantial among‐individual variation in the strength of the response. These adverse effects were intensified during unfavorable weather events, highlighting the need to reevaluate management strategies in the face of climate change.

The infralimbic mineralocorticoid blockage prevents the stress-induced impairment of aversive memory extinction in rats

Individuals deal with adversity and return to a normal lifestyle when adversity ends. Nevertheless, in specific cases, traumas may be preceded by memory distortions in stress-related malaises, and memory extinction impairment is strictly associated with the symptoms of post-traumatic stress disorder. Glucocorticoids (GCs), the central stress mediator, target mineralocorticoid (MR) and glucocorticoid (GR) receptors and coordinate stress responses. Despite MRs being present in brain regions essential to cognition, emotions, and initial stress processing, such as the medial prefrontal cortex (mPFC), most studies attempt to elucidate the stress-induced deleterious actions of GCs via GR. Therefore, it is necessary to understand the relationship between stress, infralimbic mPFC (IL), and memory and how MR-mediated intracellular signaling influences this relationship and modulates memory extinction. We observed that acutely restraint-stressed male Wistar rats showed high corticosterone (CORT) levels, and previous intra-IL-spironolactone administration (a selective MR antagonist) decreased it 60 min after the stress started. Intra-IL-CORT118335, a novel mixed MR/GR selective modulator, increased CORT throughout stress exposure. Ten days after stress, all rats increased freezing in the memory retrieval test and acquired the aversive contextual memory. During the extinction test, intra-IL injection of spironolactone, but not CORT118335, prevented the stress-impaired memory extinction, suggesting that the IL-MR activity controls CORT concentration, and it is crucial to the establishment of late extinction impairment. Also, the concomitant GR full activation overrode MR blockage. It increased CORT levels leading to the stress-induced extinction memory impairment, reinforcing that the MR/GR balance is crucial to predicting stress-induced behavioral outcomes.

Increased lead and glucocorticoid concentrations reduce reproductive success in house sparrows along an urban gradient.

Urbanization is increasing at a rapid pace globally. Understanding the links among environmental characteristics, phenotypes, and fitness enables researchers to predict the impact of changing landscapes on individuals and populations. Although avian reproductive output is typically lower in urban compared with natural areas, the underlying reasons for this discrepancy may lie at the intersection of abiotic and biotic environmental and individual differences. Recent advances in urban ecology highlight the effect of heavy metal contamination on stress physiology. As high levels of glucocorticoid hormones decrease parental investment, these hormones might be the link to decreased reproductive success in areas of high environmental pollution. In this study, we aimed to identify which abiotic stressors are linked to avian reproductive output in urban areas and whether this link is mediated by individual hormone levels. We used fine-scaled estimates (2 m2 spatial resolution) of nighttime light, noise, and urban density to assess their impacts on the physiological condition of adult house sparrows (Passer domesticus). We measured circulating levels of lead and glucocorticoid concentrations in 40 breeding pairs of free-living house sparrows and related these physiological traits to reproductive success. Using structural equation modeling, we found that increased urban density levels linked directly to increased plasma corticosterone and lead concentrations that subsequently led to decreased fledgling mass. Sparrows with increased lead concentrations in plasma also had higher corticosterone levels. Although urban areas may be attractive due to decreased natural predators and available nesting sites, they may act as ecological traps that increase physiological damage and decrease fitness. To illustrate, avian development is strongly explained by parental corticosterone levels, which vary significantly in response to urban density and lead pollution. With fine-scale ecological mapping for a species with small home ranges, we demonstrated the presence and impacts of urban stressors in a small city with high human densities.

The effects of a chalcone derivative on memory, hippocampal corticosterone and BDNF levels in adult rats

Purpose/Aim of the study: Since chalcones belong to the flavonoid family, the effects of a new synthetic chalcone derivative on memory, chronic stress, and expression of hippocampal BDNF gene were studied.Materials and methods: In this experiment, the male wistar rats were placed under restraint stress (6 h/day) for 21 days and then treated with a newly synthesized chalcone, containing methoxy on the aromatic rings or vehicles (20 mg/kg, intraperitoneal, IP). After the behavioral Passive avoidance, Open field, and Morris water maze tests, the levels of serum corticosterone (CORT) and hippocampal brain-derived neurotrophic factor (BDNF) were analyzed.Results: Results of these tests presented significant differences between the Stress (St) and Chalcone (Ch) groups. Chronic stress led to high CORT levels and impaired memory functions. Moreover, a single dose of synthetic chalcone in the St group could postpone memory impairments. Furthermore, a 20 mg/kg IP injection of chalcone markedly attenuated the decrease of hippocampal BDNF.Conclusions: It has been already proposed that flavonoids have beneficial effects on different types of memory. According to these results, further investigations are required to explore other factors besides BDNF that could be acutely modulated by chalcones.

Influence of biological sex and exercise on murine cardiac metabolism

Although the structural and functional effects of exercise on the heart are well established, the metabolic changes that occur in the heart during and after exercise remain unclear. In this study, we used metabolomics to assess time-dependent changes in the murine cardiac metabolome following 1 session of treadmill exercise. After the exercise bout, we also recorded blood lactate, glucose, and ketone body levels and measured cardiac mitochondrial respiration. In both male and female mice, moderate- and high-intensity exercise acutely increased blood lactate levels. In both sexes, low- and moderate-intensity exercise augmented circulating 3-hydroxybutryrate levels immediately after the exercise bout; however, only in female mice did high-intensity exercise increase 3-hydroxybutyrate levels, with significant increases occurring 1 h after the exercise session. Untargeted metabolomics analyses of sedentary female and male hearts suggest considerable sex-dependent differences in basal cardiac metabolite levels, with female hearts characterized by higher levels of pantothenate, pyridoxamine, homoarginine, tryptophan, and several glycerophospholipid and sphingomyelin species and lower levels of numerous metabolites, including acetyl coenzyme A, glucuronate, gulonate, hydroxyproline, prolyl-hydroxyproline, carnosine, anserine, and carnitinylated and glycinated species, as compared with male hearts. Immediately after a bout of treadmill exercise, both male and female hearts had higher levels of corticosterone; however, female mice showed more extensive exercise-induced changes in the cardiac metabolome, characterized by significant, time-dependent changes in amino acids (e.g., serine, alanine, tyrosine, tryptophan, branched-chain amino acids) and the ketone body 3-hydroxybutyrate. Results from experiments using isolated cardiac mitochondria suggest that high-intensity treadmill exercise does not acutely affect respiration or mitochondrial coupling; however, female cardiac mitochondria demonstrate generally higher adenosine diphosphate sensitivity compared with male cardiac mitochondria. Collectively, these findings in mice reveal key sex-dependent differences in cardiac metabolism and suggest that the metabolic network in the female heart is more responsive to physiological stress caused by exercise.

Proteomic and microbiota analyses of the oral cavity during psychological stress.

Psychological stress is associated with various oral diseases such as aphthous stomatitis, oral lichen planus, taste disturbances and glossodynia. However, the underlying mechanism is still unknown. The aim of this study was to determine the effect of psychological stress on salivary proteins and the oral microbiota in a rat model of chronic restraint stress. Six-week-old Sprague Dawley rats were subjected to restraint stress for four hours daily for 1 month. The behavior, weights of the adrenal glands, and serum corticosterone levels were evaluated as stress markers. Proteomic analysis of the saliva was performed using two-dimensional gel electrophoresis followed by mass spectrometry and Western blotting. Analysis of the oral microbiota was performed via 16S rRNA next-generation sequencing. The low mean body weights, lower number of entries and time spent in the open arm of elevated plus maze, high adrenal gland/body weight ratios, and high serum corticosterone levels confirmed the high levels of stress in the stress group of rats compared to the controls. Thirty-three protein spots were found to be significantly altered between the two groups. After silver staining, seven visible spots were subjected for mass spectrometry, and the expression levels of the two most significantly altered proteins, BPI fold containing family A member 2 and von Ebner’s gland protein, were confirmed by Western blotting. 16S rRNA sequencing analysis revealed a significant reduction in alpha diversity in the stress group compared to the controls. The abundances of oral bacteria, such as Facklamia and Corynebacterium, were significantly altered between the two groups. Additionally, analysis with PICRUSt2 software predicted 37 different functional pathways to be altered between the groups. In conclusion, the present study identified altered salivary proteins and oral microbiota due to psychological stress. These findings might aid in understanding the pathogenesis of stress-related oral diseases.