Stress-The International Journal on the Biology of Stress最新文献

Exosomes are nanoscale extracellular vesicles critical for intercellular communication, but their role in vertebrate stress responses remains unclear. We investigated exosome involvement in stress responses using brown anole lizards (Anolis sagrei), hypothesizing that acute stress would increase plasma exosome concentrations and inhibiting exosome secretion would attenuate the stress response. Using mixed-sex adult brown anoles (total n = 54 pairs), we conducted three experiments: a timed stress series, an adrenocorticotropic hormone (ACTH) challenge, and an exosome synthesis inhibitor (GW4869) challenge. Exosome concentrations were quantified using Nanoparticle Tracking Analysis and acetylcholinesterase (AChE) activity, while corticosterone levels were measured via enzyme-linked immunoassay (ELISA). Acute handling stress increased both plasma corticosterone and exosome concentrations, with a moderate significant correlation. ACTH injection elevated corticosterone but did not affect exosome levels. Blocking exosome synthesis with GW4869 significantly reduced corticosterone secretion, suggesting exosomes may play an indirect or concurrent role in stress regulation. This research provides the first in vivo evidence of exosomes' involvement in endocrine stress responses, offering a novel perspective on cellular stress signaling and potentially revealing an evolutionarily conserved mechanism of intercellular communication during stress adaptation.

Burnout is caused by long term psychosocial stress and has, besides the fatigue and mental health burden, been associated with increased risk of adverse physical health, such as for example type 2 diabetes. This study aims to investigate the glucose and insulin levels in individuals with stress related burnout, by assessing these metabolic markers in response to a standard oral glucose tolerance test (OGTT). 38 cases with burnout (13 men and 25 women) and 35 healthy controls (13 men and 22 women) in the age 24-55 were included in the study. The burnout group overall did not differ from healthy controls in glucose or insulin levels during the OGTT. However, the burnout cases who reported more severe burnout symptoms exhibited significantly higher levels of both glucose and insulin levels during the OGTT compared to burnout cases reporting lower severity of symptoms. Furthermore, the group of burnout cases who reported symptoms of depression exhibited higher insulin levels during OGTT compared to the burnout cases without depressive symptoms. The observed higher levels in the burnout cases with most severe symptoms indicate an increased diabetic risk in these patients and it may be of importance to follow glucose and insulin levels in individuals with more severe symptoms of burnout i.e. to perform an OGTT.

Previous reports suggest that the menstrual cycle (MC) phases can impact cortisol concentrations. However, research is needed on whether the MC impacts other markers of stress and immune function. It has also been shown that some biomarkers are impacted by time of day, although differences between morning (AM) and afternoon (PM) biomarkers have not been studied over the course of the MC. This study assessed the effect of MC phases and time of day on salivary stress biomarkers [salivary α-amylase (sAA), secretory immunoglobulin A (SIgA)], progesterone, resting blood pressure and resting heart rate (RHR). A single-group repeated measure design was employed in which seventeen participants (n = 17) monitored their MC for two months while attending eight experimental sessions which included both AM and PM sessions during each predicted 1) menses, 2) follicular, 3) ovulatory and 4) luteal phases. Resting blood pressures, heart rates, body composition parameters (assessed via bioelectrical impedance analysis), sAA and SIgA concentrations were assessed. No time of day x MC phase interactions (p > 0.05) were noted for sAA or SIgA, resting blood pressure, heart rate, or body composition parameters. However, sAA and RHR were significantly higher in the PM, while SIgA was significantly higher in the AM. These data suggest that the MC phases do not impact sAA or SIgA, resting blood pressure, heart rates, or body composition parameters. However, time-of-day impacts RHR and concentrations of sAA and SIgA. These findings provide implications for female participants in research dealing with these biomarkers.

The experience of adversity in childhood can have life-long consequences on health outcomes. In search of mediators of this relationship, alterations of bio-behavioral and cellular regulatory systems came into focus, including those dealing with basic gene regulatory processes. System biology oriented approaches have been proposed to gain a more comprehensive understanding of the complex multiple interrelations between and within layers of analysis. Here, we used co-expression based, supervised and unsupervised single and multi-omics systems approaches to investigate the association between childhood adversity and gene expression, protein expression and DNA methylation in CD14⁺ monocytes in the context of psychosocial stress exposure, in a sample of healthy adults with (n = 29) or without (n = 27) a history of childhood adversity. Childhood adversity explained some variance at the single analyte level and within gene and protein co-expression structures. A single-omics, post-stress gene expression model differentiated best between participants with a history of childhood adversity and control participants in supervised analyses. In unsupervised analyses, a multi-omics based model showed best performance but separated participants based on sex only. Multi-omics analyses are a promising concept but might yield different results based on the specific approach taken and the omics-datasets supplied. We found that stress associated gene-expression pattern were most strongly associated with childhood adversity, and integrating multiple cellular layers did not results in better discriminatory performance in our rather small sample. The capacity and yield of different omics-profiling methods might currently limit the full potential of integrative approaches.

Situations characterized by uncontrollability and critical social evaluation frustrate basic psychological needs, as outlined in Self-Determination Theory (SDT). Uncontrollability and social evaluation are central elements of the Trier Social Stress Test (TSST), leading to the hypothesis that the TSST, in addition to increasing self-reported stress and cortisol responses, also frustrates the needs for autonomy, competence, and social relatedness. Participants (N = 195) reported elevated stress and reduced need satisfaction, and increased cortisol responses during the TSST. The roles of assessed physical activity and experimentally-induced social support were also examined. Indeed, in time-sensitive and specific manner, the TSST frustrated basic psychological needs. Social support however mitigated frustration of social relatedness. Physical activity buffered against self-reported stress, the frustration of competence and the cortisol response. Further research is recommended to explore more differentiated interventions that can counteract the negative effects of psychosocial stressors.

Identifying children at risk for respiratory disorders involves understanding early risk factors. This study prospectively examines how specific types of early adversity influence childhood wheeze and how these vary by race and ethnicity. Analyses included N = 746 mother-infant dyads from an urban pregnancy cohort. Mothers completed the Lifetime Stressor Checklist-Revised (LSC-R), Edinburgh Postnatal Depression Scale (EPDS), Spielberger State-Trait Anxiety Inventory (STAI), Posttraumatic stress disorder Checklist-Civilian version (PCL-C), and Traumatic Events Screening Inventory (TESI) when infants were 6 months old to assess adverse childhood experiences (ACEs). Mothers reported child wheeze at 4-month intervals to index wheezing episodes from age 6-30 months. We first assessed independent associations between ACE measures and wheeze frequency using Poisson regression. We then used weighted quantile sum (WQS) regression to derive an ACEs mixture index to estimate joint associations with wheeze frequency in the overall sample and stratified by maternal race and ethnicity adjusting for child sex, maternal asthma and education. There was a 2.05 increase (95% CI = 1.21, 3.49) in wheeze frequency with each quintile increase of the ACEs index in Black/Black Hispanics; the TESI (72%) contributed most strongly to the mixture. In non-Black Hispanics, there was a 1.33 (95% CI = 1.05, 1.67) increase in wheeze frequency with each ACEs quintile increase with EPDS (76%) contributing most strongly. Findings support the need to move the ACEs paradigm beyond a simple cumulative score when examining effects on early respiratory disease risk. Results also highlight how the impact of early life ACEs varies by ethnoracial identity.

Atopic dermatitis (AD) is a widely recognized chronic inflammatory skin disease influenced by dietary habits, stress, genetic factors, and environmental factors. This study aimed to explore the impact of stress on AD exacerbation, as well as the associated changes in the gut microbiota. We utilized a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model subjected to chronic restraint stress (CRS). The animals were divided into four groups: normal, sham control (sham), AD, and AD+CRS. Scratching behavior was significantly increased in the AD+CRS group compared to the AD group on day 28, indicating that stress exacerbates pruritus in AD. Relative abundance analysis of the gut microbiota at the phylum level revealed an increased relative abundance of Bacteroidota in both the AD and AD+CRS groups. Principal coordinate analysis revealed distinct patterns between the AD and AD+CRS groups. The relative abundance of Heminiphilus was negatively correlated with immunoglobulin E (IgE) levels, while the relative abundance of Ruminococcus exhibited significant and negative correlations with both corticosterone and IgE levels. Alistipes, which is known to aggravate AD, was notably elevated in the AD+CRS group. These findings confirm that stress-related changes in the gut microbiota composition may contribute to the exacerbation of AD, highlighting the connection among stress, immune response, and microbiome dynamics in AD progression.

Present study was aimed to elucidate the role of corticotropin releasing hormone (CRH) neurons located in the paraventricular nucleus of the hypothalamus (PVN) in the mechanisms of stress-induced insomnia. Experiments were done in the rodent model of traumatic stress, mice exposure to the predator (rat) odor. Sleep changes associated with this model of stress were first assessed in adult male C57BL/6J wild-type mice (n = 12). The effect of chemogenetic silencing of CRH neurons within the PVN on traumatic stress-induced insomnia was examined in adult male CRH-ires-Cre mice using designer receptors exclusively activated by designer drugs (DREADD) technology. Animals received bilateral injections of inhibitory DREADD vector AAV-hSyn-DIO-hM4Di-mCherry (n = 10) or control AAV-hSyn-DIO-mCherry virus (n = 10) into the PVN during surgery. The DREADD was activated by intraperitoneal injection of clozapine-N-oxide (CNO) prior to the induction of traumatic stress. The exposure of mice to rat odor induced strong long-lasting suppression of both non-rapid eye movement (NREM) and rapid eye movement (REM) sleep stages in both experiments. Selective suppression of CRH neurons within the PVN alleviated acute insomnia by significantly increasing the time spent in NREM sleep but it did not counteract the stress-induced deficit in REM sleep. These findings suggest a specific role for CRH-secreting neurons within the PVN in the suppression of NREM sleep during acute insomnia caused by predator odor stress, whereas REM sleep suppression is controlled by a different mechanism.

Chronic stress and stress-related mental illnesses such as major depressive disorder (MDD) constitute some of the leading causes of disability worldwide with a higher prevalence in women compared to men. However, preclinical research into stress and MDD is heavily biased toward using male animals only. Aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis has been linked to the development of MDD and several animal models of MDD have been established based on HPA axis dysregulation. In the present study, we compared stress biomarkers and behavior of male and female mice after acute and chronic restraint stress to investigate potential effects of sex differences in the stress response. Further, the validity of the interrupted repeated restraint stress (IRRS) model as an animal model for the HPA axis disturbances seen in MDD was assessed. After acute stress, female mice showed increased corticosterone secretion and changes in molecular markers suggesting increased HPA axis feedback sensitivity. Acute stress-induced signs of anxiety-like behavior were observed in male mice only suggesting that female mice may be more resilient to the anxiogenic effects of acute stress. Males and females responded similarly to IRRS with no sustained perturbations in HPA axis biomarkers. The IRRS model did not adequately translate to the changes reported in MDD with HPA axis overactivity and more severe perturbation models are likely needed. However, in alignment with previous studies, these data support that there are important sex differences in the HPA axis and that these may contribute to the etiology of stress-related psychiatric disorders.

Post-traumatic stress disorder (PTSD) affects approximately one in 11 people throughout their lifetime yet current treatment options, such as behavioral therapies or pharmaceuticals, suffer from low medical adherence and often fail to fully address all the symptoms. Therefore, it is necessary to better understand maladaptive behaviors in PTSD to guide new treatments. Single-prolonged stress (SPS) is a rodent model of stress that parallels certain human neurophysiological and neurobehavioral changes occurring in PTSD. SPS is a single-day sequential stressor exposure-restraint stress, group forced swim, predator odor exposure, and isoflurane until loss of consciousness-followed by 7 days of stress incubation. Here, we investigated multiple cohorts of male C57BL/6J mice early after SPS and stress incubation (8-10 days) on behavioral tasks (elevated plus maze (EPM), three-chamber sociability, cost-benefit conflict (CBC), home cage behavior, scent avoidance and defensive burying tasks) that test multiple PTSD-related symptoms. Behavioral assessment included efforts to replicate published findings (i.e., EPM) and introducing newer tasks (i.e., CBC) that have not yet been tested in the SPS mouse model. While most of these tasks and standardized metrics failed to capture behavioral differences in SPS-treated male C57BL/6J mice, we did observe deficits in social novelty preference in the stressed mice. These studies add to a growing literature on inconsistencies in behavioral outcomes produced by the mouse SPS paradigm that could be potentially explained by mouse strain or procedural differences. Overall, this study demonstrated that behavior in male C57BL/6J mice were not affected after SPS apart from social novelty preference.