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

Suffering the stress of others (termed empathic stress or stress contagion) may affect an individual's health and well-being. To understand the underlying hormonal processes of empathic stress, N = 108 opposite-sex dyads were tested, with one dyad partner passively observing the other undergoing a standardized psychosocial laboratory stressor. A positive link between oxytocin release and empathic stress response was hypothesized, while a negative relationship was expected for testosterone release. Associations of observer oxytocin and testosterone levels with two components of empathic stress were examined: stress resonance (i.e. synchronized observer-target responses) and vicarious stress (observer responses independent of target stress). During the passive observation of a stressed target, salivary oxytocin and testosterone levels increased by 16.64% and 23.00%, respectively, followed by a drop back to baseline levels. Supporting our hypotheses, increased observer oxytocin reactivity was linked to greater stress resonance in HF-HRV reactivity. This association was reversed in low oxytocin responders. Further, testosterone reactivity was negatively associated with stress resonance in heart rate activity. However, testosterone also showed a positive association with vicarious cortisol activity, which resembles the response pattern seen in first-hand stress exposure. We conclude that stress resonance may be the more empathy-dependent component of the empathic stress construct, aligning with previous work on the involvement of oxytocin and testosterone in empathy. To draw further conclusions about the role of oxytocin and testosterone in empathic stress response, future studies including a control group and hormone stimulation are needed.

The freeze-like response is a fundamental defensive mechanism that remains poorly understood despite its potential to impair functioning under acute threat. We examined its biological correlates using untargeted serum proteomics in participants exposed to ecologically valid simulated armed attacks, comparing untrained individuals (n = 20) with experienced police rapid response personnel (n = 20). Freeze-like responses, characterized by unresponsiveness to attack, were assessed via expert video analysis of participant performance during the scenarios. Serum samples collected before and after threat exposure were analyzed via LC‒MS/MS, identifying 1,238 protein groups. Experienced personnel demonstrated markedly greater resistance to freeze-like responses. No significant proteomic changes were observed from pre- to post-exposure in either group, suggesting that freeze-resistance may be associated with stable, trait-like signatures rather than acute stress-responsive processes. Weighted gene co-expression network analysis identified a module strongly correlated with freeze-resistance (r = 0.75, p = 4 × 10^-9) and training status (r = 0.71, p = 6 × 10^-8), which also correlated with skeletal muscle mass (r = 0.57, p = 8 × 10^-5). This module was enriched for processes including extracellular matrix organization, muscle development, carbohydrate metabolism, and antioxidant activity. These molecular patterns may reflect the downstream effects of comprehensive training that integrates physical conditioning, operational experience, and psychological preparation. This study provides the first proteomic characterization of freeze-like response resistance under realistic threat conditions, supporting the view that resilience involves stable physiological adaptations rather than solely reactive stress mechanisms.

Adolescence is a sensitive window for the maturation of hypothalamic-pituitary-adrenal (HPA) axis function; however, the timing and mechanisms underlying this transition remain unclear, particularly in females and in response to repeated homotypic stress. We measured corticosterone (CORT) release and glucocorticoid-related gene expression in postpubertal (P45) and adult (P75) male and female rats after acute or repeated restraint. In males, adolescents elicited higher CORT responses than adults did after acute stress, although both ages showed habituation to repeated restraint. In contrast, females exhibited adult-like CORT responses by P45 and no evidence of habituation. At the molecular level, adolescents of both sexes displayed distinct medial prefrontal cortex and ventral hippocampus expression profiles of glucocorticoid receptor (Nr3c1) and co-chaperones (Fkbp4, Fkbp5) relative to adults, though these effects were more pronounced in females, for whom there were also age- and stress-dependent changes in mineralocorticoid receptor (Nr3c2) expression. These findings suggest that while hormonal stress responses mature earlier in females than in males, sex-specific trajectories of molecular regulation continue to develop into late adolescence, potentially shaping long-term vulnerability to stress-related disorders.

Adolescence is an important developmental period during which heightened stress reactivity and responsiveness increase susceptibility to psychiatric conditions like anxiety and depression. Studies with rodent models have primarily tested the effects of chronic, rather than acute, stress on the development of anxiety- and depression-like behaviors, and many have not included female subjects. The current study examined whether a single acute stress exposure in female rats can induce anxiety-like and depression-like behaviors, and whether the timing of the stress, early (postnatal day 28) versus mid-adolescence (postnatal day 36), influences these outcomes. We used a PTSD-relevant stress paradigm that paired acute immobilization with fox-urine predator odor. Female Sprague-Dawley rats completed a battery of behavioral assays to characterize anxiety-like (elevated plus maze, open field test) and depression-like behaviors (sucrose preference test, forced swim test) between 12 and 16 days postexposure. Acute stress during adolescence caused an increase in anxiety-like behavior, regardless of whether stress occurred in early or mid-adolescence. No increase in depression-like behaviors was observed. Our findings suggest that a single exposure to a predator odor when paired with immobilization is sufficient to increase anxiety-like but not depression-like behaviors in female adolescent rats.

Elevated blood pressure is commonly linked to diminished pain perception, a phenomenon known as blood pressure-related hypoalgesia. Interoception, the ability to perceive and interpret internal bodily signals, has been previously linked to both blood pressure and pain perception, although findings in the literature remain mixed. We investigated the relationship between blood pressure, pain perception, and interoception under both non-stressful (Pilot Study) and stressful (Main Study) conditions. In the Pilot Study, resting measures of blood pressure, pain thresholds and interoception were assessed in 26 healthy participants. Regression analysis revealed that higher systolic blood pressure was associated with increased pain thresholds, in line with previous findings. In the Main Study, the same variables were assessed in 46 healthy participants at rest and when a stress condition was induced by a validated virtual reality stress paradigm (i.e. the IMVEST). The effectiveness of the stress induction was confirmed through physiological measures (heart rate, heart rate variability, cortisol) and psychological assessments (perceived stress). No significant changes in blood pressure or pain threshold were observed following stress exposure. However, moderation analyses revealed that systolic blood pressure moderated the relationship between interoceptive beliefs (measured via the MAIA questionnaire) and pain perception: a positive association between the tendency to notice internal bodily sensations and pain threshold emerged only in individuals with high systolic blood pressure. This relationship was not observed in individuals with average or low systolic blood pressure. Taken together, these findings suggest that individual differences in cardiovascular physiology and interoceptive processes may shape pain perception.

Depression is one of the most common health concerns all around the globe. Valproic acid (VPA) is an anticonvulsant agent, with neuroprotective, anti-apoptotic, anti-inflammatory, and antidepressant effects in animal models. We carried out a systematic review of articles that reported the effect of VPA on stress-related depression in animal models. A search of databases was conducted with keywords related to valproic acid (VPA) and stress-induced depression. Data from the Forced Swimming Test (FST), Open Field Test (OFT), Novel Object Recognition (NOR), and Sucrose Preference Test (SPT) were extracted. Meta-analysis was conducted using Stata 14, and standardized mean differences (SMD) were calculated. Quality control and subgroup analysis were carried out. Meta-analysis of FST results obtained from 16 separate experiments showed that VPA had a strong effect in reducing the percentage immobility, signifying lower stress compared to the untreated group (SMD = -0.93; 95% CI = -1.66 to -0.21; p = 0.012). When administered via injection for four consecutive weeks, VPA at a dosage of 300 mg/kg/day significantly decreased depressive symptoms. Results from the vertical OFT in seven studies and the horizontal OFT in six studies indicated that VPA increased movement scores. SPT results in nine separate experiments showed that VPA significantly increased the animals' desire to drink sucrose water. Analysis of the NOR test demonstrated that VPA had no significant effects on the ability of animals to identify a new object. Our findings suggest that VPA can exert antidepressant-like effects in rat models of stress-induced depression, but heterogeneity and potential publication bias suggests caution is required.

Stress and anxiety are prevalent mental health conditions that often coexist with cardiovascular comorbidities, resulting in a complex interplay between psychological and physiological processes, partly mediated through activation of the hypothalamic-pituitary-adrenal (HPA) axis. Ashwagen®, a standardized extract of Withania somnifera (Ashwagandha), has demonstrated adaptogenic and anxiolytic properties in preclinical and clinical studies. This study aimed to evaluate the safety and efficacy of Ashwagen® in managing stress and anxiety in patients with pre-existing hypertension and associated cardiometabolic risk factors. A randomized, double-blind, placebo-controlled Phase III clinical trial was conducted over 60 days in 60 patients diagnosed with stress, anxiety, and pre-existing hypertension with cardiometabolic risk profiles. Participants received either Ashwagen® (300 mg capsule) or placebo twice daily. Efficacy assessments included validated psychological scales-Hamilton Anxiety Rating Scale (HAM-A), Generalized Anxiety Disorder-7 (GAD-7), Perceived Stress Scale (PSS), Clinical Global Impression-Improvement (CGI-I), Epworth Sleepiness Scale (ESS), and Fatigue Severity Scale (FSS)-along with serum cortisol, triglycerides, LDL, and blood pressure measurements. Ashwagen® significantly reduced anxiety and stress markers compared with placebo. HAM-A, GAD-7, and PSS scores decreased by 26.94%, 50.77%, and 30.47%, respectively, in the Ashwagen® group. Cortisol levels declined by 28.99% and triglycerides by 13.00%, with favorable trends in LDL and blood pressure. No serious adverse events were reported. Ashwagen® was found to be a safe and effective adjunctive integrative intervention for stress and anxiety management in patients with pre-existing hypertension.

Heat stress is a condition that develops when the body absorbs more heat than it can dissipate, leading to hyperthermia and problems such as gastrointestinal dysfunction. Past research suggests that gut dysfunction is highly temperature sensitive, and hyperthermia that alters the gut myoelectric activity should be studied properly through electrogastrography. Ten rats, 5 as controls and 5 as hyperthermic, were used in the experiment. For control conditions, a real-time electrogastrogram (EGG) recording was performed at room temperature, and for the induction of hyperthermia, a 42 ± 1 °C temperature was maintained in a closed incubator for 60 min. The rectal temperature was also taken before and after the exposure. The FFT of a full-length recording and five segments, each of 15 min, were analyzed; the wave shift and total time of occurrence of each wave were closely observed. As per the experiment, more spike pattern waves were observed in the hyperthermic rat model (p < 0.01) compared to the control rat, as the heat stress triggers changes in autonomic nervous activity, particularly through the parasympathetic and sympathetic pathways. This imbalance could lead to increased or irregular gastric electrical activity, converting slow waves to spikes. More spike patterns in EGG were observed due to exposure to hyperthermic conditions, which may have occurred due to gut inflammation, altered gastric motility, as well as ion channel dysregulation.

Chronic stress induces neurobiological alterations within limbic circuits. The contribution of hippocampal histaminergic signaling to stress-related behavioral dysfunction remains insufficiently characterized. This study examined the comparative and combined effects of fluoxetine and treadmill exercise on anxiety- and depression-like behaviors and ventral hippocampal histamine H1 and H2 receptor expression in a chronic unpredictable mild stress (CUMS) rat model. Male Wistar rats were exposed to four weeks of CUMS and allocated to seven groups: Control, CUMS, Exercise (EXC), Fluoxetine (FLX), CUMS+EXC, CUMS+FLX, and CUMS+FLX+EXC. Anxiety-like behavior was assessed using the elevated plus maze (EPM) and open field test (OFT), while depressive-like behavior was evaluated using the forced swim test (FST). Hippocampal H1 and H2 receptor mRNA levels were quantified by real-time PCR. CUMS induced significant anxiety- and depression-like behaviors, evidenced by reduced central zone exploration and increased FST immobility. Fluoxetine significantly attenuated depressive-like behavior, while combined fluoxetine and exercise increased open-arm exploration in the EPM. CUMS significantly upregulated hippocampal H1 and H2 receptor mRNA expression relative to controls. Neither fluoxetine nor exercise alone significantly reversed these stress-induced elevations. Combined treatment produced partial attenuation of H1 receptor upregulation, whereas H2 receptor expression remained elevated across treatment conditions. These findings demonstrate that chronic stress induces robust hippocampal histaminergic remodeling that persists despite behavioral improvement, suggesting that histaminergic signaling is a stress-responsive molecular substrate only partially sensitive to conventional antidepressant strategies. The dissociation between behavioral recovery and receptor normalization identifies the hippocampal histaminergic system as a potential target for future therapeutic intervention in stress-related disorders.

Synthetic predator scents such as trimethylthiazoline (TMT) evoke innate fear responses in rodents, reflecting evolutionarily conserved defense mechanisms. Previous studies have shown that after repeated exposure to innate fear stimuli would induce adaptive processes, including habituation and desensitization, which may involve additional neural circuits apart from the amygdala, particularly the hippocampus, which is involved in various forms of learning and memory. To elucidate whether the habituation induced by repeated exposure to innate fear stress is associated with plasticity in the hippocampus, the present study examined whether repeated exposure to TMT (i) attenuates innate fear responses and (ii) affects hippocampal neurogenesis. Twenty male Sprague Dawley rats were randomly assigned to the control (distilled water) or TMT-exposed groups for 14 days. Behavioral assays on anxiety- and depression-like behaviors were assessed after the exposure period. Serum samples were collected 2-3 days following the exposure, while neurogenesis and cell differentiation in brain tissues were analyzed. The results demonstrated that repeated TMT exposure facilitated fear habituation. Interestingly, no significant changes in anxiety- or depression-like behaviors were found even when exposure to TMT is regarded as a stressful stimulation. Additionally, hippocampal cell proliferation increased, and the total number of immature neurons decreased after repeated exposure to TMT. Instead of neurons, there is a significant increase in the proportion of new cells that adopt an astrocytic fate. The current results support that stress due to predator odor promotes hippocampal proliferation, inhibits neurogenesis, and alters glial cell fate adoption, which reveals a complex structural remodeling under repeated TMT exposure and fear habituation.