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

Mary Dallman has left a legacy in neuroendocrinology, not only as the scientist who elaborated on new concepts such as rapid corticosteroid feedback pathways, but also as a role model, particularly for women who followed in her footsteps. In this contribution, I compare (i) the remarkable journey she made toward her position as the first female faculty member ever at the physiology department at USCF with that of generations after her; (ii) the contribution of our labs on rapid corticosteroid actions; and, (iii) finally, our experiences with unexpected findings for which one should always keep an open mind, a standpoint that was fervently advocated by Mary Dallman.

Stress is a normal response to situational pressures or demands. Exposure to stress activates the hypothalamic-pituitary-adrenal (HPA) axis and leads to the release of corticosteroids, which act in the brain via two distinct receptors: mineralocorticoid receptors (MR) and glucocorticoid receptors (GR). Persistent HPA axis overactivation or dysregulation can disrupt an individual's homeostasis, thereby contributing to an increased risk for mental illness. On the other hand, successful coping with stressful events involves adaptive and cognitive processes in the brain that render individuals more resilient to similar stressors in the future. Here we review the role of the MR in these processes, starting with an overview of the physiological structure, ligand binding, and expression of MR, and further summarizing its role in the brain, its relevance to psychiatric disorders, and related rodent studies. Given the central role of MR in cognitive and emotional functioning, and its importance as a target for promoting resilience, future research should investigate how MR modulation can be used to alleviate disturbances in emotion and behavior, as well as cognitive impairment, in patients with stress-related psychiatric disorders.

Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Shirom-Melamed Burnout Questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which could go unnoticed in cognitive testing but still be reflected in the experience of deficits in everyday cognitive functioning.

Bombesin receptor-activated protein (BRAP) and its homologous protein in mice, which is encoded by bc004004 gene, were expressed abundantly in brain tissues with unknown functions. We treated bc004004^-/- mice with chronic unpredictable mild stress (CUMS) to test whether those mice were more vulnerable to stress-related disorders. The results of forced swimming test, sucrose preference test, and open field test showed that after being treated with CUMS for 28 days or 35 days both bc004004^-/- and bc004004^+/+ mice exhibited behavioural changes and there was no significant difference between bc004004^+/+ and bc004004^-/-. However, behavioural changes were observed only in bc004004^-/- mice after being exposed to CUMS for 21 days, but not in bc004004^+/+ after 21-day CUMS exposure, indicating that lack of BRAP homologous protein may cause vulnerability to stress-related disorders in mice. In addition, bc004004^-/- mice showed a reduction in recognition memory as revealed by novel object recognition test. Since memory changes and stress related behavioural changes are all closely related to the hippocampus function we further analyzed the changes of dendrites and synapses of hippocampal neurons as well as expression levels of some proteins closely related to synaptic function. bc004004^-/- mice exhibited decreased dendritic lengths and increased amount of immature spines, as well as altered expression pattern of synaptic related proteins including GluN2A, synaptophysin and BDNF in the hippocampus. Those findings suggest that BRAP homologous protein may have a protective effect on the behavioural response to stress via regulating dendritic spine formation and synaptic plasticity in the hippocampus.

Acute stress can impair human working memory. Little is known, however, about the effects of acute stress on working memory strategies. The goal of this research was to investigate the effects of acute stress on use of a systematic spatial working memory search strategy. Participants (28 females and 20 males per group) completed the Trier Social Stress Test (TSST) or control tasks. Use of a systematic spatial working memory search strategy was measured through performance on the spatial working memory subtest of the Cambridge Neuropsychological Test Automated Battery (CANTAB). The TSST was effective at producing subjective and cortisol stress responses, but there was no significant stress effect on use of a systematic search strategy or working memory search errors. There were also no significant relationships between subjective and cortisol stress responses and use of a systematic search strategy or working memory search errors within the stress group. These results suggest that acute stress does not impair the self-generation or execution of a systematic spatial working memory search strategy.

Greater cortisol reactivity to stress is often assumed to lead to heightened negative affective reactivity to stress. Conversely, a growing body of evidence demonstrates mood-protective effects of cortisol elevations in the context of acute stress. We administered a laboratory-based stressor, the Trier Social Stress Test (TSST), and measured cortisol and emotional reactivity in 68 adults (48 women) between the ages of 25 and 65. In accordance with our pre-registered hypothesis (https://osf.io/t8r3w) and prior research, negative affective reactivity was inversely related to cortisol reactivity assessed immediately after the stressor. We found that greater cortisol response to acute stress is associated with smaller increases in negative affect, consistent with mood-protective effects of cortisol elevations in response to acute stress.

Chronic sleep disorders (CSD) comprise a potential risk factor for metabolic and cardiovascular diseases, obesity and stroke. Thus, the identification of biomarkers for CSD is an important step in the early prevention of metabolic dysfunctions induced by sleep dysfunction. Diagnostic saliva samples can be easily and noninvasively collected. Thus, we aimed to identify whole microRNA (miRNA) profiles of saliva in control and psychophysiologically stressed CSD mouse models and compare them at Zeitgeber time (ZT) 0 (lights on) and ZT12 (lights off). The findings of two-way ANOVA revealed that the expression of 342 and 109 salivary miRNAs was affected by CSD and the time of day, respectively. Interactions were found in 122 miRNAs among which, we identified 197 (ZT0) and 62 (ZT12) upregulated, and 40 (ZT0) and seven (ZT12) downregulated miRNAs in CSD mice. We showed that miR-30c-5p, which is elevated in the plasma of patients with hypersomnia, was upregulated in the saliva of CSD mice collected at ZT0. The miRNAs, miR-10a-5p, miR-146b-5p, miR-150-5p, and miR-25-3p are upregulated in the serum of humans with poor sleep quality, and these were also upregulated in the saliva of CSD mice collected at ZT0. The miRNAs miR-30c, miR146b-5p, miR150, and miR-25-5p are associated with cardiovascular diseases, and we found that plasma concentrations of brain natriuretic peptides were significantly increased in CSD mice. The present findings showed that salivary miRNA profiles could serve as useful biomarkers for predicting CSD.

Childhood adversity might impair corticolimbic brain regions, which play a crucial role in emotion processing and the acute stress response. The dimensional model of childhood adversity proposed that deprivation and threat dimensions might associated with individuals' development through different mechanisms. However, few studies have explored the relationship between different dimensions of childhood stress, emotion processing, and acute stress reactivity despite the overlapping brain regions of the last two. With the aid of the event-related potentials technique, we explore whether negative emotion processing, which might be particularly relevant for adaptive stress responding among individuals with adverse childhood experience, mediates the relationship between dimensional childhood stress and acute stress response. Fifty-one young adults completed a free-viewing task to evaluate neural response to negative stimuli measured by late positive potential (LPP) of ERPs (Event-related potentials). On a separate day, heart rate and salivary cortisol were collected during a social-evaluative stress challenge (i.e. TSST, Trier Social Stress Test). After the TSST, the childhood trauma questionnaire was measured to indicate the level of abuse (as a proxy of threat) and neglect (as a proxy of deprivation) dimensions. Multiple linear regression and mediation analysis were used to explore the relationship among childhood stress, emotion processing, and acute stress response. Higher level of childhood abuse (but not neglect) was distinctly related to smaller LPP amplitudes to negative stimuli, as well as smaller heart rate reactivity to acute stress. For these participants, smaller LPP amplitudes were linked with smaller heart rate reactivity to acute stress. Furthermore, decreased LPP amplitudes to negative stimuli mediated the relationship between higher level of childhood abuse and blunted heart rate reactivity to stress. Consistent with the dimensional model of childhood stress, our study showed that childhood abuse is distinctly associated with neural as well as physiological response to threat. Furthermore, the blunted neural response to negative stimuli might be the underlying mechanism in which childhood abuse leads to the blunted acute stress response. Considering that all the participants are healthy in the present study, the blunted processing of negative stimuli might rather reflect adaptation instead of vulnerability, in order to prevent stress overshooting in the face of early-life threatening experiences.

Prolonged or severe stress has been found to inhibit the hypothalamic-pituitary-gonadal axis (HPG) and its testosterone release. In contrast, acute stress, including competition, social evaluation, or physical challenges, shows more inconsistent response patterns. This study examined changes in cortisol and testosterone across different types and durations of stress in the same individuals. We further explored the influence of baseline levels on hormonal stress responses. Sixty-seven male officer cadets in the Swiss Armed Forces (mean age 20.46 years ± 1.33) were assessed during two different acute stressors-the Trier Social Stress Test for Groups (TSST-G) and a brief military field exercise-and in the long-term during the 15-week officer training school. Several saliva samples were collected before and after the acute stressors for cortisol and testosterone. Morning testosterone was assessed four times during officer training school. There were significant increases in cortisol and testosterone during the TSST-G and the field exercise. Baseline levels of testosterone were negatively associated with acute cortisol response during the field exercise but not during the TSST-G. Morning saliva testosterone decreased during the first 12 weeks of officer training school and increased again in week 15, with no differences to baseline levels. The findings suggest that group stress tests such as the TSST-G or field exercises in groups may be particularly challenging for young men. The results also point to an adaptive role of testosterone during acute challenges during prolonged stress.

The sense of agency (SoA) refers to the feeling of being in control of one's actions and the subsequent consequence of these actions. Emotional context seems to alter the strength of sense of agency. The present study explored the influence of acute psychosocial stress on the SoA by means of the Trier Social Stress Test (TSST). Self-assessment manikin (SAM) and objective physiological indicators (e.g. heart rate, electrodermal activity, and salivary cortisol levels) were utilized to evaluate the effect of the TSST. We also employed the temporal binding effect as an implicit assessment of the participant's SoA. The results indicated that the stress level of the experimental group after TSST was significantly higher than the control group, whilst the temporal binding scores of the experimental group decreased after TSST manipulation. In short, acute psychosocial stress with intense emotional arousal weakened the sense of agency.