Corticosterone and glucose are correlated and show similar response patterns to temperature and stress in a free-living bird.

Glucocorticoid (GC) hormones have traditionally been interpreted as indicators of stress, but the extent to which they provide information on physiological state remains debated. GCs are metabolic hormones that amongst other functions ensure increasing fuel (i.e. glucose) supply on the face of fluctuating energetic demands, a role often overlooked by ecological studies investigating the consequences of GC variation. Furthermore, because energy budget is limited, in natural contexts where multiple stimuli coexist, the organisms ability to respond physiologically may be constrained when multiple triggers of metabolic responses overlap in time. Using free-living spotless starling (Sturnus unicolor) chicks, we experimentally tested whether two stimuli of different nature known to trigger a metabolic or GC response respectively cause a comparable increase in plasma GCs and glucose. We further tested whether response patterns differed when both stimuli occurred consecutively. We found that both experimental treatments caused increases in GCs and glucose of similar magnitude, suggesting that both variables fluctuate along with variation in energy expenditure, independently of the trigger. Exposure to the two stimuli occurring subsequently did not cause a difference in GC or glucose responses compared to exposure to a single stimulus, suggesting a limited capacity to respond to an additional stimulus during an ongoing acute response. Lastly, we found a positive and significant correlation between plasma GCs and glucose after the experimental treatments. Our results add-up to the increasing research on the role of energy expenditure on GC variation, by providing experimental evidence on the association between plasma GCs and energy metabolism.

Advancement in perioperative management of pituitary adenomas-Current concepts and best practices.

Pituitary adenomas are very common representing 18.1% of all brain tumors and are the second most common brain pathology. Transsphenoidal surgery is the mainstay of treatment for all pituitary adenomas except for prolactinomas which are primarily treated medically with dopamine agonists. A thorough endocrine evaluation of pituitary adenoma preoperatively is crucial to identify hormonal compromise caused by the large sellar mass, identifying prolactin-producing tumors and comorbidities associated with Cushing and acromegaly to improve patient care and outcome. Transsphenoidal surgery is relatively safe in the hands of experienced surgeons, but still carries a substantial risk of causing hypopituitarism that required close follow-up in the immediate postoperative period to decrease mortality. A multidisciplinary team approach with endocrinologists, ophthalmologists, and neurosurgeons is the cornerstone in the perioperative management of pituitary adenomas.

Male-Biased Vulnerability of Mouse Brain Tryptophan/Kynurenine and Glutamate Systems to Adolescent Exposures to Concentrated Ambient Ultrafine Particle Air Pollution.

Air pollution (AP) exposures have been associated with numerous neurodevelopmental and psychiatric disorders, including autism spectrum disorder, attention deficit hyperactivity disorder and schizophrenia, all male-biased disorders with onsets from early life to late adolescence/early adulthood. While prior experimental studies have focused on effects of AP exposures during early brain development, brain development actually extends well into early adulthood. The current study in mice sought to extend the understanding of developmental brain vulnerability during adolescence, a later but significant period of brain development and maturation to the ultrafine particulate (UFPs) component of AP, considered its most reactive component. Additionally, it examined adolescent response to UFPs when preceded by earlier developmental exposures, to ascertain the trajectory of effects and potential enhancement or mitigation of adverse consequences. Outcomes focused on shared features associated with multiple neurodevelopmental disorders. For this purpose, C57Bl/6J mice of both sexes were exposed to ambient concentrated UFPs or filtered air from PND (postnatal day) 4-7 and PND10-13, and again at PND39-42 and 45-49, resulting in 3 exposure postnatal/adolescent treatment groups per sex: Air/Air, Air/UFP, and UFP/UFP. Features common to neurodevelopmental disorders were examined at PND50. Mass exposure concentration from postnatal exposure averaged 44.34 µg/m3 and the adolescent exposure averaged 49.18 µg/m3. Male brain showed particular vulnerability to UFP exposures in adolescence, with alterations in frontal cortical and striatal glutamatergic and tryptophan/serotonergic neurotransmitters and concurrent reductions in levels of astrocytes in corpus callosum and in serum cytokine levels, with combined exposures resulting in significant reductions in corpus callosum myelination and serum corticosterone. Reductions in serum corticosterone in males correlated with reductions in neurotransmitter levels, and reductions in striatal glutamatergic function specifically correlated with reductions in corpus callosum astrocytes. UFP-induced changes in neurotransmitter levels in males were mitigated by prior postnatal exposure, suggesting potential adaptation, whereas reductions in corticosterone and in corpus callosum neuropathological effects were further strengthened by combined postnatal and adolescent exposures. UFP-induced changes in females occurred primarily in striatal dopamine systems and as reductions in serum cytokines only in response to combined postnatal and adolescent exposures. Findings in males underscore the importance of more integrated physiological assessments of mechanisms of neurotoxicity. Further, these findings provide biological plausibility for an accumulating epidemiologic literature linking air pollution to neurodevelopmental and psychiatric disorders. As such, they support a need for consideration of the regulation of the UFP component of air pollution.

TRPV1 and mast cell involvement in repeated variate stress (RVS) induced urinary bladder dysfunction in adult female mice.

The etiology of interstitial cystitis/bladder pain syndrome (IC/BPS) is unknown but likely multifactorial. IC/BPS symptoms can be exacerbated by psychological stress, but underlying mechanisms remain to be defined. TRPV1 channels, expressed on nerve fibers, have been implicated in bladder dysfunction and colonic hypersensitivity with stress in rodents. Histamine/H1R activation of TRPV1+ nerves increases bladder afferent fiber sensitivity to distension. TRPV1 channels are also expressed on mast cells, previously implicated in contributing to IC/BPS etiology and symptoms. We have examined the contribution of TRPV1 and mast cells to bladder dysfunction after repeated variate stress (RVS). RVS increased (p ≤ 0.05) serum and fecal corticosterone expression and induced anxiety-like behavior in wild type (WT) mice. Intravesical instillation of the selective TRPV1 antagonist capsazepine (CPZ) rescued RVS-induced bladder dysfunction in WT mice. Trpv1 knockout (KO) mice did not increase voiding frequency with RVS and did not exhibit increased serum corticosterone expression despite exhibiting anxiety-like behavior. Mast cell deficient mice (B6.Cg-Kitw-sh) failed to demonstrate RVS-induced increased voiding frequency or serum corticosterone expression whereas control (no stress) mast cell deficient mice had similar functional bladder capacity to WT mice. TRPV1 protein expression was significantly increased in the rostral lumbar (L1-L2) spinal cord and dorsal root ganglia in WT mice exposed to RVS but no changes were observed in lumbosacral (L6-S1) spinal segments or DRG. These studies demonstrated TRPV1 and mast cell involvement in RVS-induced increased voiding frequency and suggest that TRPV1 and mast cells may be useful targets to mitigate stress-induced urinary bladder dysfunction.

Amplifying hepatic L-aspartate levels suppresses CCl4-induced liver fibrosis by reversing glucocorticoid receptor ß-mediated mitochondrial malfunction.

Liver fibrosis is a determinant-stage process of many chronic liver diseases and affected over 7.9 billion populations worldwide with increasing demands of ideal therapeutic agents. Discovery of active molecules with anti-hepatic fibrosis efficacies presents the most attacking filed. Here, we revealed that hepatic L-aspartate levels were decreased in CCl4-induced fibrotic mice. Instead, supplementation of L-aspartate orally alleviated typical manifestations of liver injury and fibrosis. These therapeutic efficacies were alongside improvements of mitochondrial adaptive oxidation. Notably, treatment with L-aspartate rebalanced hepatic cholesterol-steroid metabolism and reduced the levels of liver-impairing metabolites, including corticosterone (CORT). Mechanistically, L-aspartate treatment efficiently reversed CORT-mediated glucocorticoid receptor ß (GRß) signaling activation and subsequent transcriptional suppression of the mitochondrial genome by directly binding to the mitochondrial genome. Knockout of GRß ameliorated corticosterone-mediated mitochondrial dysfunction and hepatocyte damage which also weakened the improvements of L-aspartate in suppressing GRß signaling. These data suggest that L-aspartate ameliorates hepatic fibrosis by suppressing GRß signaling via rebalancing cholesterol-steroid metabolism, would be an ideal candidate for clinical liver fibrosis treatment.

The Influence of Maternal Hypoxia and Buspirone during Pregnancy on Cognitive Abilities and a Stress Response in Adult Male Offspring.

Spatial learning, memory, and reactivity of the hypothalamic-pituitary-adrenocortical system (HPA axis) were studied in adult male rats, whose mothers during pregnancy were subjected to acute moderate normobaric hypoxia, or repeated injections of buspirone, an agonist of type 1A serotonergic receptors (5HT1A), or their combination. Prenatal treatment with buspirone in rats with prenatal hypoxia impaired learning ability during the first day of 5-day training. A decrease in the effectiveness of long-term memory in comparison with short-term memory was revealed in two groups of rats: prenatal treatment with buspirone in combination with hypoxia and injection of physiological saline without hypoxia. The effectiveness of long-term memory and the level of corticosterone in response to stress did not differ between the groups, which can indicate adaptation of the 5HT1A receptor and the HPA axis to the prenatal buspirone and normobaric hypoxia during ontogeny.

Corticosterone disrupts spatial working memory during retention testing when highly taxed, which positively correlates with depressive-like behavior in middle-aged, ovariectomized female rats.

Major Depressive Disorder affects 8.4 % of the U.S. population, particularly women during perimenopause. This study implemented a chronic corticosterone manipulation (CORT, a major rodent stress hormone) using middle-aged, ovariectomized female rats to investigate depressive-like behavior, anxiety-like symptoms, and cognitive ability. CORT (400 µg/ml, in drinking water) was administered for four weeks before behavioral testing began and continued throughout all behavioral assessments. Compared to vehicle-treated rats, CORT significantly intensified depressive-like behaviors: CORT decreased sucrose preference, enhanced immobility on the forced swim test, and decreased sociability on a choice task between a novel conspecific female rat and an inanimate object. Moreover, CORT enhanced anxiety-like behavior on a marble bury task by reducing time investigating tabasco-topped marbles. No effects were observed on novelty suppressed feeding or the elevated plus maze. For spatial working memory using an 8-arm radial arm maze, CORT did not alter acquisition but disrupted performance during retention. CORT enhanced the errors committed during the highest working memory load following a delay and during the last trial requiring the most items to remember; this cognitive metric positively correlated with a composite depressive-like score to reveal that as depressive-like symptoms increased, cognitive performance worsened. This protocol allowed for the inclusion of multiple behavioral assessments without stopping the CORT treatment needed to produce a MDD phenotype and to assess a battery of behaviors. Moreover, that when middle-age was targeted, chronic CORT produced a depressive-like phenotype in ovariectomized females, who also comorbidly expressed aspects of anxiety and cognitive dysfunction.

The effect of late-life environmental enrichment on stress and anxiety: The role of sex and age-related differences in coping with aversive stimuli.

Anxiety significantly diminishes the quality of life in older adults, and the drugs used for its treatment often come with risky side effects. Non-pharmacological protocols could be valuable, but more research is needed in this area. Environmental enrichment induces positive effects on anxiety-like behavior in young and adult animals; whether the same happens in aged animals is still elusive. The aged brain undergoes changes that contribute to make it "fragile" and consequently even mild, potentially positive stimuli can trigger dyshomeostasis, worsening rather than ameliorating functioning. Here, by combining behavioral analysis and measurement of serum and brain corticosterone levels, we show that late-life environmental enrichment can induce eustress or distress, depending on sex and hypothalamic-pituitary-adrenal axis function. These findings pave the way for optimizing outcomes and minimizing undesired effects in the clinical setting, underscoring the need to overcome the limits of gender medicine and emphasizing the crucial role of individually tailored therapies.

Early-life stress impairs acquisition and retrieval of fear memories: sex-effects, corticosterone modulation, and partial prevention by targeting glucocorticoid receptors at adolescent age.

The early postnatal period is a sensitive time window that is characterized by several neurodevelopmental processes that define neuronal architecture and function later in life. Here, we examined in young adult mice, using an auditory fear conditioning paradigm, whether stress during the early postnatal period 1) impacts fear acquisition and memory consolidation in male and female mice; 2) alters the fear responsiveness to corticosterone and 3) whether effects of early-life stress (ELS) can be prevented by treating mice with a glucocorticoid (GR) antagonist at adolescence. Male and female mice were exposed to a limited nesting and bedding model of ELS from postnatal day (PND) 2-9 and injected i.p with RU38486 (RU486) at adolescent age (PND 28-30). At two months of age, mice were trained in the fear conditioning (FC) paradigm (with and without post training administration of corticosterone - CORT) and freezing behavior during fear acquisition and contextual and auditory memory retrieval was scored. We observed that ELS impaired fear acquisition specifically in male mice and reduced both contextual and auditory memory retrieval in male and female mice. Acute post-training administration of CORT increased freezing levels during auditory memory retrieval in female mice but reduced freezing levels during the tone presentation in particular in control males. Treatment with RU486 prevented ELS-effects in acquisition in male mice and in females during auditory memory retrieval. In conclusion, this study highlights the long-lasting consequences of early-life stress on fear memory processing and further illustrates 1) the potential of a glucocorticoid antagonist intervention during adolescence to mitigate these effects and 2) the partial modulation of the auditory retrieval upon post training administration of CORT, with all these effects being sex-dependent.

Developmental activity-based anorexia alters hippocampal non-genomic stress response and induces structural instability and spatial memory impairment in female rats.

OBJECTIVE: Anorexia nervosa (AN) is characterized by hyperactivation of the hypothalamic-pituitary-adrenal axis and cognitive deficits. However, little is known about the rapid non-genomic stress response involvement. This study investigates the molecular, structural and behavioral signatures of the anorexic phenotype induction in female rats on stress-related mechanisms in the hippocampus. METHOD: Female adolescent rats, exposed to the combination of food restriction and wheel access, i.e., the activity-based anorexia (ABA) protocol, were sacrificed in the acute phase of the pathology (postnatal day [P]42) or following a 7-day recovery period (P49). RESULTS: ABA rats, in addition to body weight loss and increased wheel activity, alter their pattern of activity over days, showing increased food anticipatory activity, a readout of their motivation to engage in intense physical activity. Corticosterone plasma levels were enhanced at P42 while reduced at P49 in ABA rats. In the membrane fraction of the hippocampus, we found reduced glucocorticoid receptor levels together with reduced expression of caldesmon, n-cadherin and neuroligin-1, molecular markers of cytoskeletal stability and glutamatergic homeostasis. Accordingly, structural analyses revealed reduced dendritic spine density, a reduced number of mushroom-shaped spines, together with an increased number of thin-shaped spines. These events are paralleled by impairment in spatial memory measured in the spatial order object recognition test. These effects persisted even when body weight of ABA rats was restored. DISCUSSION: Our findings indicate that ABA induction orchestrates hippocampal maladaptive structural and functional plasticity, contributing to cognitive deficits, providing a putative mechanism that could be targeted in AN patients.

Nutritional and physiological responses to dietary phosphorus levels and phytase in pullets and laying hens.

The objective of this study was to determine the effects of dietary available phosphorus (P) levels and dietary phytase added into the very low-P diet on the performance, mineral balance, odor emission, and stress responses in growing pullets and laying hens during 13 to 32 wk of age. One hundred sixty-eight pullets (Hy-Line Brown) were randomly assigned into 1 of 4 dietary treatments with 7 replicates of 6 birds each. Experimental diets were formulated to contain 3 graded P levels at 0.25, 0.35, and 0.45% during 13 to 15 wk (phase 1), 0.25, 0.35, and 0.45% during 16 to 18 wk (phase 2), and 0.20, 0.30, and 0.40% during 19 to 32 wk (phase 3). In addition, dietary phytase (500 FTU/kg matrix values) was added into the very low-P diets (0.20% during 13-15 wk, 0.25% during 16-18 wk, and 0.20% during 19-32 wk) to meet the nutritional adequacy with standard P diets. In all phases, decreasing dietary P levels did not affect (P > 0.05) growth, laying performance, and egg qualities. Decreasing dietary P levels linearly increased the relative duodenal and oviduct weights (P < 0.05), and quadratically increased the relative ovary weight in pullets (P = 0.016). Dietary phytase lowered (P = 0.021) the relative duodenal weight compared with the very low-P diet. Tibia breaking strength and tibia Mg contents in pullets were linearly lowered (P < 0.05) as dietary P levels decreased. Dietary phytase tended to increase (P = 0.091) tibia breaking strength and significantly increased (P = 0.025) tibia Mg content compared with the very low-P diet. Dietary P levels and dietary phytase affected (P < 0.05) ileal crypt depth and ileal villus height: crypt depth ratio in pullets. Decreasing dietary P levels linearly decreased (P < 0.01) crude fat digestibility and P excretion in both pullets and laying hens. Dietary phytase reversed (P < 0.05) the very low-P diet-mediated decrease of crude fat digestibility in pullets and laying hens. Dietary P levels and dietary phytase affected (P < 0.05) odor emission including ammonia in pullets and total volatile fatty acids in laying hens. Finally, lowering dietary P levels increased (P < 0.01) yolk corticosterone concentrations and the increased corticosterone concentration by the very low-P diet was reversed by dietary phytase. Collectively, our study shows that decreasing dietary P levels induced nutritional and physiological responses in pullets and laying hens and these P-mediated negative effects were mitigated by dietary phytase.

Metabolic Responses to High-Fat Feeding and Chronic Psychological Stress Combination.

INTRODUCTION: High-fat diet (HFD) consumption and being exposed to daily psychological stress, common environmental factors in modern lifestyle, play an important role on metabolic disorders such as glucose homeostasis impairment. The aim of this study was to investigate the effects of high-fat diet (HFD) and psychological stress combination on metabolic response to chronic psychological stress in male rats. METHOD: Male Wistar rats were divided into HFD, and normal diet (ND) groups and then into stress and nonstress subgroups. The diets were applied for 5 weeks, and psychological stress was induced for 7 consecutive days. Then, blood samples were taken to measure glucose, insulin, free fatty acids (FFA), and leptin and corticosterone concentrations. Subsequently, glucose-stimulated insulin release from pancreatic isolated islets was assessed. RESULTS: HFD did not significantly change fasting plasma glucose, insulin and corticosterone levels, whereas increased plasma leptin (7.05 ± 0.33) and FFA (p < 0.01) levels and impaired glucose tolerance. Additionally, HFD and stress combination induced more profound glucose intolerance associated with increased plasma corticosterone (p < 0.01) and leptin (8.63 ± 0.38) levels. However, insulin secretion from isolated islets did not change in the presence of high-fat diet and/or stress. CONCLUSION: HFD should be considered as an intensified factor of metabolic impairments caused by chronic psychological stress.

Circadian Synchronization of Feeding Attenuates Rats' Food Restriction-Induced Anxiety and Amygdalar Thyrotropin-Releasing Hormone Downregulation.

Anxiety is a common comorbidity of obesity, resulting from prescribing long-term caloric restriction diets (CRDs); patients with a reduced food intake lose weight but present anxious behaviors, poor treatment adherence, and weight regain in the subsequent 5 years. Intermittent fasting (IF) restricts feeding time to 8 h during the activity phase, reducing patients' weight even with no caloric restriction; it is unknown whether an IF regime with ad libitum feeding avoids stress and anxiety development. We compared the corticosterone blood concentration between male Wistar rats fed ad libitum or calorie-restricted with all-day or IF food access after 4 weeks, along with their anxiety parameters when performing the elevated plus maze (EPM). As the amygdalar thyrotropin-releasing hormone (TRH) is believed to have anxiolytic properties, we evaluated its expression changes in association with anxiety levels. The groups formed were the following: a control which was offered food ad libitum (C-adlib) or 30% of C-adlib's energy requirements (C-CRD) all day, and IF groups provided food ad libitum (IF-adlib) or 30% of C-adlib's requirements (IF-CRD) with access from 9:00 to 17:00 h. On day 28, the rats performed the EPM and, after 30 min, were decapitated to analyze their amygdalar TRH mRNA expression by in situ hybridization and corticosterone serum levels. Interestingly, circadian feeding synchronization reduced the body weight, food intake, and animal anxiety levels in both IF groups, with ad libitum (IF-adlib) or restricted (IF-CRD) food access. The anxiety levels of the experimental groups resulted to be negatively associated with TRH expression, which supported its anxiolytic role. Therefore, the low anxiety levels induced by synchronizing feeding with the activity phase would help patients who are dieting to improve their diet therapy adherence.

Alpha-synuclein-induced stress sensitivity renders the Parkinson's disease brain susceptible to neurodegeneration.

A link between chronic stress and Parkinson's disease (PD) pathogenesis is emerging. Ample evidence demonstrates that the presynaptic neuronal protein alpha-synuclein (asyn) is closely tied to PD pathogenesis. However, it is not known whether stress system dysfunction is present in PD, if asyn is involved, and if, together, they contribute to neurodegeneration. To address these questions, we assess stress axis function in transgenic rats overexpressing full-length wildtype human asyn (asyn BAC rats) and perform multi-level stress and PD phenotyping following chronic corticosterone administration. Stress signaling, namely corticotropin-releasing factor, glucocorticoid and mineralocorticoid receptor gene expression, is also examined in post-mortem PD patient brains. Overexpression of human wildtype asyn leads to HPA axis dysregulation in rats, while chronic corticosterone administration significantly aggravates nigrostriatal degeneration, serine129 phosphorylated asyn (pS129) expression and neuroinflammation, leading to phenoconversion from a prodromal to an overt motor PD phenotype. Interestingly, chronic corticosterone in asyn BAC rats induces a robust, twofold increase in pS129 expression in the hypothalamus, the master regulator of the stress response, while the hippocampus, both a regulator and a target of the stress response, also demonstrates elevated pS129 asyn levels and altered markers of stress signalling. Finally, defective hippocampal stress signalling is mirrored in human PD brains and correlates with asyn expression levels. Taken together, our results link brain stress system dysregulation with asyn and provide evidence that elevated circulating glucocorticoids can contribute to asyn-induced neurodegeneration, ultimately triggering phenoconversion from prodromal to overt PD.

Individual quality overwrites carry-over effects across the annual cycle of a long-distance migrant.

In seasonal environments, the fitness of animals depends upon the successful integration of life-history stages throughout their annual cycle. Failing to do so can lead to negative carry-over effects where individuals are transitioning into the next season in different states, consequently affecting their future performance. However, carry-over effects can be masked by individual quality when individuals vary in their efficiency at acquiring resources year after year (i.e. 'quality'), leading to cross-seasonal consistency in individual performance. Here we investigated the relative importance of carry-over effects and individual quality in determining cross-seasonal interactions and consequences for breeding success over the full annual cycle of a migratory seabird (black-legged kittiwake Rissa tridactyla). We monitored the reproduction and annual movement of kittiwakes over 13 years using geolocators to estimate their breeding success, distribution and winter energy expenditure. We combined this with an experimental approach (clutch removal experiment, 2 years) to manipulate the reproductive effort irrespective of individual quality. Piecewise path analyses showed that successful breeders reproduced earlier and were more likely to breed successfully again the following year. This positive interaction among consecutive breeding stages disappeared after controlling for individual quality, suggesting that quality was dominant in determining seasonal interactions. Moreover, controlling experimentally for individual quality revealed underlying carry-over effects that were otherwise masked by quality, with breeding costs paid in higher energy expenditure and delayed onset of reproduction. We highlight the need to combine an experimental approach along with long-term data while assessing apparent carry-over effects in wild animals, and their potential impact on fitness and population demography.

Testosterone regulates thymic remodeling by activating glucocorticoid receptor signaling pathway to accelerate thymocyte apoptosis in male rats.

Thymic atrophy affects T cell generation and migration to the periphery, thereby affecting T cell pool diversity. However, the mechanisms underlying thymic atrophy have not been fully elucidated. Here, gonadotropin-releasing hormone (GnRH) immunization and surgical castration did not affect thymocyte proliferation, but significantly reduced the apoptosis and increased the survival rate of CD4-CD8-, CD4+CD8+, CD4+CD8-, and CD4-CD8+ thymocytes. Following testosterone supplementation in rats subjected to GnRH immunization and surgical castration, thymocyte proliferation remained unchange, but the apoptosis of CD4-CD8-, CD4+CD8+, CD4+CD8-, and CD4-CD8+ thymocytes significantly increased. Transcriptome analyses of the thymus after GnRH immunization and surgical castration showed a significant reduction in the thymus's response to corticosterone. Cholesterol metabolism and the synthesis and secretion of corticosterone were significantly reduced. Analysis of the enzyme levels involved in the corticosterone synthesis pathway revealed that corticosterone synthesis in thymocytes was significantly reduced after GnRH immunization and surgical castration, whereas exogenous testosterone supplementation relieved this process. Testosterone promoted thymocyte apoptosis in a concentration-dependent manner, and induced corticosterone secretion in vitro. Blocking the intracellular androgen receptor (AR) signaling pathway did not significantly affect thymocyte apoptosis, but blocking the glucocorticoid receptor (GR) signaling pathway significantly reduced it. Our findings indicate that testosterone regulates thymus remodeling by affecting corticosterone synthesis in thymocytes, which activates GR signal transduction and promotes thymocyte apoptosis.

Androgen and glucocorticoid profiles throughout extended uniparental paternal care in the eastern hellbender salamander (Cryptobranchus a. alleganiensis).

The behavioral endocrinology associated with reproduction and uniparental male care has been studied in teleosts, but little is known about hormonal correlates of uniparental male care in other ectotherms. To address this gap, we are the first to document the seasonal steroid endocrinology of uniparental male hellbender salamanders during the transition from pre-breeding to nest initiation, and through the subsequent eight months of paternal care. In doing so, we investigated the correlates of nest fate and clutch size, exploring hellbenders' alignment with several endocrinological patterns observed in uniparental male fish. Understanding the endocrinology of hellbender paternal care is also vital from a conservation perspective because high rates of nest failure were recently identified as a factor causing population declines in this imperiled species. We corroborated previous findings demonstrating testosterone and dihydrotestosterone (DHT) to be the primary androgens in hellbender reproduction, and that cortisol circulates as the most abundant glucocorticoid. However, we were unable to identify a prolactin or a "prolactin-like" peptide in circulation prior to or during parental care. We observed âˆ¼ 80 % declines in both primary androgens during the transition from pre-breeding to nest initiation, and again as paternal care progressed past its first month. In the days immediately following nest initiation, testosterone and DHT trended higher in successful individuals, but did not differ with males' clutch size. We did not observe meaningful seasonality in baseline glucocorticoids associated with breeding or nesting. In contrast, stress-induced glucocorticoids were highest at pre-breeding and through the first two months of care, before declining during the latter-most periods of care as larvae approach emergence from the nest. Neither baseline nor stress-induced glucocorticoids varied significantly with either nest fate or clutch size. Both stress-induced cortisol and corticosterone were positively correlated with total length, a proxy for age in adult hellbenders. This is consistent with age-related patterns in some vertebrates, but the first such pattern observed in a wild amphibian population. Generally, we found that nesting hellbenders adhere to some but not all of the endocrinological patterns observed in uniparental male teleosts prior to and during parental care.

Time-dependent dual mode of action of COX-2 inhibition on mouse serum corticosterone levels.

To elucidate the effect of cyclooxygenase-2 (COX-2) inhibition on corticosterone release, mice were divided into a group receiving NS398, a selective COX-2 inhibitor at a dose of 3 mg/kg for seven days, and a group receiving NS398 for fourteen days. After this time, the mice were sacrificed, and blood serum was collected. An ELISA protocol was used to analyze serum corticosterone levels. Short-term COX-2 inhibition increased corticosterone levels, while long-term inhibition lowered them. The exact schedule of experiments was repeated after the lipopolysaccharide (LPS) Escherichia coli challenge in mice to check the influence of stress stimuli on the tested parameters. In this case, we observed increases in corticosterone levels, significant in a seven-day pattern. These results indicate that corticosterone levels are regulated through a COX-2-dependent mechanism in mice.

Adolescent stress accelerates postpartum novelty recognition impairment in 5xFAD mice.

Pregnancy and the postpartum period induce physiological changes that can influence women's cognitive functions. Alzheimer's disease (AD) has a higher prevalence in women and is exacerbated by early life stress. In the present study, we found that late adolescent social isolation combined with the experience of pregnancy and delivery accelerates the onset of cognitive deficits in 5xFAD dams, particularly affecting their ability to recognize novelty. These cognitive deficits manifested as early as 16 weeks, earlier than the usual timeline for these mice, and were closely associated with increased levels of corticosterone, suggesting dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis. Notably, the presence of ß-amyloid plaques in brain regions associated with novelty recognition did not significantly contribute to these deficits. This highlights the potential role of stress and HPA axis dysregulation in the development of cognitive impairments related to AD, and underscores the need for further investigation.

Understanding the role of early life stress and schizophrenia on anxiety and depressive like outcomes: An experimental study.

BACKGROUND: Adverse experiences due to early life stress (ELS) or parental psychopathology such as schizophrenia (SZ) have a significant implication on individual susceptibility to psychiatric disorders in the future. However, it is not fully understood how ELS affects social-associated behaviors as well as the developing prefrontal cortex (PFC). OBJECTIVE: The aim of this study was to investigate the impact of ELS and ketamine induced schizophrenia like symptoms (KSZ) on anhedonia, social behavior and anxiety-like behavior. METHODS: Male and female Sprague-Dawley rat pups were allocated randomly into eight experimental groups, namely control, gestational stress (GS), GS+KSZ, maternal separation (MS), MS+KSZ pups, KSZ parents, KSZ parents and Pups and KSZ pups only. ELS was induced by subjecting the pups to GS and MS, while schizophrenia like symptoms was induced through subcutaneous administration of ketamine. Behavioral assessment included sucrose preference test (SPT) and elevated plus maze (EPM), followed by dopamine testing and analysis of astrocyte density. Statistical analysis involved ANOVA and post hoc Tukey tests, revealing significant group differences and yielding insights into behavioral and neurodevelopmental impacts. RESULTS: GS, MS, and KSZ (dams) significantly reduced hedonic response and increased anxiety-like responses (p < 0.05). Notably, the presence of normal parental mental health demonstrated a reversal of the observed decline in Glial Fibrillary Acidic Protein-positive astrocytes (GFAP+ astrocytes) (p < 0.05) and a reduction in anxiety levels, implying its potential protective influence on depressive-like symptoms and PFC astrocyte functionality. CONCLUSION: The present study provides empirical evidence supporting the hypothesis that exposure to ELS and KSZ on dams have a significant impact on the on development of anxiety and depressive like symptoms in Sprague Dawley rats, while positive parenting has a reversal effect.