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

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.

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.

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.

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.

Recent years brought considerable attention to the connection between chronic stress and the development of autoimmune diseases. However, little is still known about the impact of prolonged stress reactions on the onset and course of primary Sjögren Syndrome (pSS). This study aimed to seek for associations between chronic stress, resulting from stressful life events, and pSS. In the study, 50 patients with diagnosed pSS, as well as 50 control patients with osteoarthritis underwent an assessment. Modified Holmes-Rahe (H-R) stress scale was used in order to evaluate the impact of stressful events within 12 months prior to the diagnosis. Patients with pSS had a significantly higher total score on H-R stress scale within one-year preceding the disease diagnosis (152 ± 66.3 vs 50 ± 54.6; p $<$ 0.001). Additionally, the pSS patients more commonly than the controls reported a subjectively perceived correlation between stressful events and the occurrence of disease symptoms (50% vs 12%; p $<$ 0.001). Moreover, the H-R score at the time of the assessment correlated with the disease activity. The results support the view that pSS belongs to the group of diseases which pathogenesis is closely related to stressful life events. The novelty of this work lies in focus on both the correlation of stress on the onset of autoimmune disease as well as the activity of previously diagnosed disorder. Our data contributes to finding evidence-based medicine (EBM) arguments to what has until recently been merely a thematic observation-the harmfulness of negative stress on individual's health status.

Women are twice as likely than men to develop an anxiety disorder after stress exposure stress, a sex-specific vulnerability that arises after puberty. This suggests that pubertal hormones could contribute to the central changes induced by stress and leading to behavioral deregulations. The main brain regions involved in stress-induced psychopathologies are part of the limbic system, including the prefrontal cortex (PFC), the basolateral amygdala (BLA) and the ventral hippocampus (vHipp). Changes in their activity are often reported after stress, contributing to appearance of behavioral symptoms. We aimed at determining whether female pubertal hormones modulate the effects of chronic stress on activity of these limbic regions to identify a potential mechanism underlying the female vulnerability to stress-induced pathologies. Prepubertal adolescent female mice underwent ovariectomy (OVX) or sham surgery. In late adolescence, they started 4 weeks of unpredictable chronic mild stress (UCMS). We used immunohistochemistry to quantify FosB/ΔFosB, a marker of chronic activity, in the PFC, BLA, and vHipp. Prepubertal OVX increased activity of the PFC and decreased activity of the BLA and vHipp, while UCMS had little impact. The PFC was more significantly impacted by both OVX and UCMS, with each of these manipulations increasing number of FosB/ΔFosB+ cells, however without interactive effects. Correlation analyses indicate that level of activity in the PFC and vHipp correlates with measures of anxiety. However, the gonadal status influences strongly these relationships. Our data indicate that pubertal hormones could play a role in the regulation of anxiety through their long-lasting impact on the limbic system.

Sleep deprivation (SD) is known to induce neurocognitive dysfunction, with hippocampal inflammation emerging as a critical mediator. Electroacupuncture has shown efficacy in modulating inflammation in neurological disorders, but its potential in mitigating SD-induced cognitive impairment remains underexplored. Using a murine model, we investigated the effects of electroacupuncture on hippocampal inflammation and cognitive function following SD treatment. BALB/c mice underwent sleep disruption using a multiple-platform apparatus and were subsequently treated with electroacupuncture. Cognitive function was assessed using the Morris Water Maze and Y-maze tests. Electroacupuncture treatment significantly ameliorated SD-induced cognitive impairment, as evidenced by improved performance in spatial memory tasks. Additionally, electroacupuncture attenuated hippocampal inflammation, characterized by reduced levels of pro-inflammatory cytokines (IL-1β, MCP-1 and TNF-α) and increased expression of the anti-inflammatory cytokine IL-10. Mechanistically, electroacupuncture suppressed microglial activation and inhibited the TLR4/NF-κB signaling pathway within the hippocampus. Electroacupuncture has therapeutic potential in mitigating SD-induced cognitive dysfunction by modulating hippocampal inflammation, which offers a promising non-pharmacological approach for preserving cognitive function in sleep-deprived individuals.

Previous studies have shown that corticosterone rapidly alters extracellular serotonin (5-hydroxytryptamine; 5-HT) concentrations in the dorsomedial hypothalamus (DMH) of adult male rats, suggesting a role for corticosterone actions in the DMH in regulation of physiological and behavioral responses. Whether or not corticosterone also rapidly alters extracellular serotonin concentrations in the DMH of female rats, and the dependence of this effect on ovarian hormones, is not known. To determine the effects of 17β-estradiol (E₂), progesterone (P), and corticosterone on extracellular concentrations of serotonin in the DMH, corticosterone and/or P were delivered into the DMH of ovariectomized rats via reverse microdialysis in E₂-primed rats. Combined, but not separate, delivery of corticosterone and P into the DMH rapidly and transiently increased extracellular 5-HT concentrations, a result that was dependent upon circulating E₂. This effect of corticosterone on DMH 5-HT was replicated by local perfusion of the organic cation transporter 3 (OCT3) competitive inhibitor normetanephrine. Intra-DMH infusions of either corticosterone or normetanephrine also reversibly suppressed lordosis responses in E₂ + P-primed females. These results suggest that ovarian hormones in combination with corticosterone modulate OCT3-mediated 5-HT clearance in the DMH, potentially representing an adaptive mechanism that allows sexually receptive females to respond rapidly to acute stressors.

Chronic stress leads to hypofunction of the medial prefrontal cortex (mPFC), mechanisms of which remain to be determined. Enhanced activation of GABAergic of parvalbumin (PV) expressing interneurons (INs) is thought to play a role in stress-induced prefrontal inhibition. In this study, we tested whether chemogenetic inhibition of mPFC PV INs after chronic stress can rescue chronic stress-related behavioral and physiological phenotypes. Mice underwent 2 weeks of chronic variable stress (CVS) followed by a battery of behavioral tests known to be affected by chronic stress exposure, e.g. an open field (OF), novel object recognition (NOR), tail suspension test (TST), sucrose preference test (SPT), and light dark (LD) box. Inhibitory DREADDs were actuated by 3 mg/kg CNO administered 30 min prior to each behavioral test. CVS caused hyperactivity in the OF, reduced sucrose preference in the SPT (indicative of enhanced anhedonia), and increased anxiety-like behavior in the LD box. Inhibition of PV IN after stress mitigated these effects. In addition, CVS also resulted in reduced thymus weight and body weight loss, which were also mitigated by PV IN inhibition. Our results indicate that chronic stress leads to plastic changes in PV INs that may be mitigated by chemogenetic inhibition. Our findings implicate cortical GABAergic INs as a therapeutic target in stress-related diseases.