Acute Stress Induction Research Articles

Acute Stress Improves Concentration Performance

Acute stress can have both detrimental and beneficial effects on cognitive processing, but effects on concentration performance remain unclear. Here, we investigate the effects of acute psychosocial stress on concentration performance and possible underlying physiological and psychological mechanisms. The study sample comprised 47 healthy male participants who were randomly assigned either to a psychosocial stress situation (Trier Social Stress Test) or a neutral control task. Concentration performance was assessed using the d2 Test of Attention before and 30 min after the stress or control task. Salivary cortisol and alpha-amylase were repeatedly measured before and up to 1 hr after stress. We repeatedly assessed state anxiety using the State-Trait Anxiety Inventory and anticipatory cognitive stress appraisal using the Primary Appraisal Secondary Appraisal questionnaire. The stress group showed a significantly stronger improvement of concentration performance compared to the control group (p = .042). Concentration performance improvement was predicted by increased state anxiety (p = .020) and lower cortisol (stress) changes (p = .043). Neither changes in alpha-amylase nor cognitive stress appraisal did relate to concentration performance. Our results show improved concentration performance after acute psychosocial stress induction that was predicted by higher state anxiety increases and lower cortisol increases. This points to a potential modulating role of specific psycho-emotional and physiological factors with opposite effects.

An investigation of the relations between stress and prospective memory

ABSTRACT Prospective memory (PM), or remembering to perform intentions in the future, has important implications for one’s daily functioning and quality of life. Another common human experience is stress. Despite the significance and ubiquity of both PM and stress, our understanding of the relations between them is limited. The aim of the current study was to further delineate the relations between acute stress, chronic stress, non-focal event-based PM, and time-based PM. The results of the study revealed that acute stress induction after PM intention formation did not contribute to differences in non-focal event-based PM performance or time-based PM performance. However, self-reported chronic stress was significantly correlated with enhanced monitoring and time-based PM. In the present study, participants may have had optimal levels of enduring stress that contributed to enhanced monitoring behaviour (i.e. the prospective component of PM) and the ability to complete time-based intentions.

Acute stress alters neural patterns of value representation for others

Acute stress is often evoked during social interactions, by feelings of threat or negative evaluation by other people. We also constantly interact with others while under stress – in the workplace or in private alike. However, it is not clear how stress affects social interactions. For one, individuals could become more selfish and focused on their own goals. On the other hand, individuals might also become more focused on affiliating with potential social partners, in order to secure their support. There is, indeed, accumulating behavioral evidence that prosocial behaviors increase rather than decrease under stress. Here, we tested the underlying brain processes of such findings, by assessing the effects of stress on the neural representations of (monetary) value for self and other. Participants (N ​= ​30; male, 18–40 years) played a gambling task for themselves and for another participant while undergoing functional magnetic resonance imaging (fMRI). Each participant played the gambling task twice: once immediately following acute stress induction, and once in a control session. We compared neural patterns of value representation in the dorsomedial prefrontal cortex (dmPFC), ventromedial prefrontal cortex (vmPFC) and striatum using representational similarity analysis (RSA). We found that under stress, dmPFC and striatum showed higher dissimilarity between neural patterns underlying high and low value for the other. Dissimilarity of neural patterns underlying high and low value for the self was unaffected by stress. These findings suggest that participants track the magnitude of possible rewards for others more under stress, suggesting increased prosocial orientation.

The effects of psychosocial stress on dopaminergic function and the acute stress response.

Chronic psychosocial adversity induces vulnerability to mental illnesses. Animal studies demonstrate that this may be mediated by dopaminergic dysfunction. We therefore investigated whether long-term exposure to psychosocial adversity was associated with dopamine dysfunction and its relationship to psychological and physiological responses to acute stress. Using 3,4-dihydroxy-6-[18F]-fluoro-l-phenylalanine ([18F]-DOPA) positron emission tomography (PET), we compared dopamine synthesis capacity in n = 17 human participants with high cumulative exposure to psychosocial adversity with n = 17 age- and sex-matched participants with low cumulative exposure. The PET scan took place 2 hr after the induction of acute psychosocial stress using the Montréal Imaging Stress Task to induce acute psychosocial stress. We found that dopamine synthesis correlated with subjective threat and physiological response to acute psychosocial stress in the low exposure group. Long-term exposure to psychosocial adversity was associated with dampened striatal dopaminergic function (p=0.03, d = 0.80) and that psychosocial adversity blunted physiological yet potentiated subjective responses to acute psychosocial stress. Future studies should investigate the roles of these changes in vulnerability to mental illnesses.

Kinetics and Interrelations of the Renin Aldosterone Response to Acute Psychosocial Stress: A Neglected Stress System.

ContextThe renin-angiotensin-aldosterone system (RAAS) plays an important role in cardiovascular homeostasis and its dysfunction relates to negative health consequences. Acute psychosocial stress seems to activate the RAAS in humans, but stress kinetics and interrelations of RAAS parameters compared with a nonstress control group remain inconclusive.ObjectiveWe systematically investigated in a randomized placebo-controlled design stress kinetics and interrelations of the reactivity of RAAS parameters measured in plasma and saliva to standardized acute psychosocial stress induction.Methods58 healthy young men were assigned to either a stress or a placebo control group. The stress group underwent the Trier Social Stress Test (TSST), while the control group underwent the placebo TSST. We repeatedly assessed plasma renin, and plasma and salivary aldosterone before and up to 3 hours after stress/placebo. We simultaneously assessed salivary cortisol to validate successful stress induction and to test for interrelations.ResultsAcute psychosocial stress induced significant increases in all endocrine measures compared with placebo-stress (all P ≤ .041). Highest renin levels were observed 1 minute after stress, and highest aldosterone and cortisol levels 10 and 20 minutes after stress, with salivary aldosterone starting earlier at 1 minute after stress. Renin completed recovery at 10 minutes, cortisol at 60 minutes, salivary aldosterone at 90 minutes, and plasma aldosterone at 180 minutes after stress. Stress increase scores of all endocrine measures related to each other, as did renin and cortisol areas under the curve with respect to increase (AUCi) and salivary and plasma aldosterone AUCi (all P ≤ .047).ConclusionsOur findings suggest that in humans acute psychosocial stress induces a differential and interrelated RAAS parameter activation pattern. Potential implications for stress-related cardiovascular risk remain to be elucidated.

Reduction of acute mild stress corticosterone response and changes in stress-responsive gene expression in male Balb/c mice after repeated administration of a Rhodiola rosea L. root extract.

Rhodiola rosea L. (R. rosea) is an adaptogenic plant increasing body resistance to stress. Its efficacy has been evidenced mainly in chronic stress models, data concerning its effect in acute stress and underlying mechanisms being scarce. The objective was to investigate the effect of repeated doses of a R. rosea hydroethanolic root extract (HRE) on hypothalamic pituitary adrenal response in a murine model of acute mild stress and also the mechanisms involved. Stress response was measured in Balb/c mice having received by gavage HRE (5 g/kg) or vehicle daily for 2 weeks before being submitted to an acute mild stress protocol (open‐field test then elevated plus maze). Corticosterone was measured in plasma from mandibular vein blood drawn before and 30, 60, and 90 min after initiation of the stress protocol. Mice were sacrificed at 90 min, and the hippocampus, prefrontal cortex, and amygdala were excised for high‐frequency RT‐PCR gene expression analysis. At 30 min after acute mild stress induction, corticosterone level in mice having received the HRE was lower than in control mice and comparable to that in nonstressed mice in the HRE group. HRE administration induced brain structure‐dependent changes in expression of several stress‐responsive genes implicated in neuronal structure, HPA axis activation, and circadian rhythm. In the acute mild stress model used, R. rosea HRE decreased corticosterone level and increased expression of stress‐responsive genes, especially in the hippocampus and prefrontal cortex. These findings suggest that R. rosea HRE could be of value for modulating reactivity to acute mild stress.

Hypothalamic-pituitary-adrenal axis responsivity to an acute novel stress in female rats subjected to the chronic mild stress paradigm

The chronic mild stress (CMS) paradigm is the most frequently investigated animal model for major depression. The hypothalamic-pituitary-adrenal (HPA) axis participates in the generation of depressive symptomatology. We examined whether the depression-like state induced by CMS is associated with immediate changes in HPA axis activation in response to a novel acute stress and whether this response could be modified by hormonal status. Adult female Wistar rats were ovariectomized and received estrogen or vehicle pellets. After 2 weeks, rats were subjected to CMS (or control) conditions for 2.5 or 4.5 weeks. Rats were subsequently subjected to restraint stress for 1 h, and plasma corticosterone (CT) levels were determined before (2:00 p.m.) and after acute stress induction (3:00 and 4:00 p.m.). CT levels and FOS expression were measured in the medial parvocellular subdivision of the PVN (PaMP), central (CeA) and medial amygdala (MeA) and ventral subiculum of the hippocampus (vSub). Plasma CT levels in animals treated with 6.5 weeks of estrogen were elevated before and 1 h after restraint stress induction. Results indicate that the estrogen chronicity and CMS exposure impacted CT secretion. Neuronal PaMP, CeA, MeA and vSub activity decreased after 4.5 weeks of CMS in all groups. No differences were detected between CMS and non-CMS groups. These data suggest that the HPA central hyporesponsiveness observed in the experimental groups subjected to a longer protocol period was independent to CMS paradigm and estrogen treatment restored partially its activity. These data suggest that additional stressors could be responsible for the observed alterations of the HPA axis.

Oxidative Stress Impairs Fatty Acid Oxidation and Mitochondrial Function in the Term Placenta.

Placental fatty acid oxidation (FAO) is impaired and lipid storage is increased in pregnancy states associated with chronic oxidative stress. The effect of acute oxidative stress, as seen in pregnancies complicated with asthma, on placental lipid metabolism is unknown. We hypothesized that induction of acute oxidative stress would decrease FAO and increase esterification. We assessed [3H]-palmitate oxidation and esterification in term placental explants from lean women after exposure to hydrogen peroxide (H2O2) for 4 hours. Fatty acid oxidation decreased 16% and 24% in placental explants exposed to 200 (P = .02) and 400 µM H2O2 (P = .01), respectively. Esterification was not altered with H2O2 exposure. Neither messenger RNA nor protein expression of key genes involved in FAO (eg, peroxisome proliferator-activated receptor α, carnitine palmitoyl transferase 1b) were altered. Adenosine triphosphate (ATP) levels decreased with induction of oxidative stress, without increasing cytotoxicity. Acute oxidative stress decreased FAO and ATP production in the term placenta without altering fatty acid esterification. As decreases in placental FAO and ATP production are associated with impaired fetal growth, pregnancies exposed to acute oxidative stress may be at risk for fetal growth restriction.

Evaluating the effects of dietary resistant starch on growth, digestion, metabolism, immunity and resistance to ammonia stress in Litopenaeus vannamei

Resistant starch (RS) is considered to be a good alternative to antibiotics. A 56‐day feeding trial was followed by induction of acute ammonia stress to evaluate the effects of dietary RS on growth, digestion, metabolism, immunity and resistance to ammonia stress in Litopenaeus vannamei. The four diets used differed only in RS content: 0 g/kg (Control), 10 g/kg (RS1), 30 g/kg (RS2) and 50 g/kg (RS3). The results showed that dietary RS improved the growth and the survival rates of shrimp exposed to ammonia stress. At 56 days, the activity of digestive and metabolic enzymes (amylase, lipase, pepsin, hexokinase and pyruvate kinase) was increased in the three RS groups, while trypsin activity only increased in the RS1 and RS2 groups; immune‐related parameters (the total antioxidant capacity; the activity of superoxide dismutase, total nitric oxide synthase and phenoloxidase; and the expression of heat‐shock protein 70, thioredoxin, prophenoloxidase, lysozyme and toll gene) were increased in the three RS groups. After exposure to ammonia stress, all the selected immune parameters of the three RS groups were higher than those of the control group at 24 hr. Therefore, dietary RS improved the growth, digestion, metabolism, immunity and resistance to ammonia stress in L. vannamei.

Stress hormone effects on accuracy and generalization of memory

Following an aversive experience, fears often generalize across contexts. Contextual fear generalization is modeled in a laboratory paradigm in which one context (CTX+) is paired with an aversive unconditional stimulus (US), while the other context (CTX-) is not. The current study sought to validate a novel paradigm assessing contextual fear generalization, and to determine the extent to which stress and anxiety symptoms enhanced contextual fear generalization.Fifty-nine participants were randomized to a stress induction or control arithmetic test, followed by a differential context fear conditioning paradigm. One to three days later, participants completed a generalization gradient test with CTX+, CTX, and four generalization contexts.We found successful contextual fear conditioning on measures of US expectancy, self-report fear and valence, and startle reflex, and linear generalization across the contextual gradient on expectancies and self-report measures. Acute stress induction impaired learning of the US-CTX + association during context fear acquisition. Anxiety significantly predicted greater contextual fear generalization as measured by US expectancy.Our study provides pilot data introducing a novel fear conditioning paradigm to assess contextual generalization of fear. There is a need for further replication to validate its utility.Findings suggest that individuals high in anxiety show greater contextual fear generalization as measured by US expectancy. Results are discussed in terms of potential mechanisms that contribute to pervasive anxiety.

Mood Disorders: Protection of the Hyper-Excited Brain, or a Risk Factor?

Emotional disturbances such as anxiety, fear, depression and aggression are often experienced by patients with temporal lobe epilepsy. These psychiatric symptoms may occur during or just after (postictal) a seizure; however, in some patients, they occur interictally (i.e. between seizures) and may profoundly change the individual’s personality. Aside from confirming that a significant proportion of temporal lobe epileptics do suffer from interictal abnormal emotionality, there has been little progress to date in identifying the fundamental nature of these disturbances. There is a lack of evidences regarding the influence of activation of emotiogenic structures and emotional behavior on development of seizures. Kindling is a commonly used animal model for study of interictal emotionality and the effects of kindling and human epilepsy on emotional behavior are the primary focus of investigators and not vice versa. Respectively, the interrelation between emotional and seizure reactions was studied in Wistar albino rats. In our study we tried to elucidate: can emotional behavior evoked by stimulation of the emotiogenic zones of the hypothalamus or of induction of acute pain stress modify manifestations of generalized seizures within the period where a “full” epileptic syndrom has been stable formed earlier? Our leading hypothesis is as follow: the emotional disturbances can be considered as the emergence of instinctive behavior with an adaptive significance of defense and as a by-product of the inhibitory processes that build up to protect against the future occurrence of seizures.

Acute Stress Attenuates Cognitive Flexibility in Males Only: An fNIRS Examination.

Cognitive processes that afford us the ability to control thoughts and achieve goal-directed behavior are known as executive functions. Empirical evidence in the past few years has demonstrated that executive functions can be influenced by acute stress. The impact of acute stress on cognitive flexibility, a key aspect of executive functions, has received little attention in the literature. We present the results of two experiments conducted to examine the effect of acute stress on cognitive flexibility. Acute stress was induced using the cold pressor task. Cognitive flexibility was assessed using the Wisconsin Card Sorting Test (WCST). Across both experiments acute stress had an attenuating effect on task switching on the WCST. Our findings also indicate that this effect was moderated by the participant’s gender. In Study 1, we observed that following stress exposure male participants in the stress condition made more perseverative errors than participants in the control group. In Study 2, we examined the bilateral hemodynamics in the prefrontal cortex (PFC) during acute stress induction using functional near infrared spectroscopy (fNIRS). Our analysis indicated that functional oxyHb signals fluctuated with greater amplitude than systemic components for participants in the stress group relative to those in the control group. In addition, oxyHb levels post stress induction were correlated with performance on the WCST for the male participants in the stress group only. Concordant with previous reports, our findings indicate that acute stress impacts cognitive flexibility in males and females differentially. Our work also demonstrates the feasibility of using fNIRS as a practical and objective technique for the examination of hemodynamics in the PFC during acute stress.

The influence of the noradrenergic/stress system on perceptual biases for reward.

Previous research has established a role for the norepinephrine (NE)/stress system in individual differences in biases to attend to reward or punishment. Outstanding questions concern its role in the flexibility with which such biases can be changed. The goal of this preregistered study was to examine the role of the NE/stress system in the degree to which biases can be trained along the axis of valence in the direction of reward. Participants genotyped for a common deletion variant of ADRA2b (linked to altered NE availability) experienced either an acute stress induction or a control procedure. Following stress induction, a "bias probe" task was presented before and after training. In the bias probe task, participants made forced choice judgments (happy or angry) on emotional faces with varying degrees of ambiguity. For bias training, participants viewed unambiguously angry faces in a task exploiting visual adaptation effects. The results revealed an overall shift from a slightly positive bias in categorizing faces pretraining to a more positive bias after training. Carriers of the deletion variant overall showed a more positive bias than did the noncarriers. Follow-up analyses showed that pretraining bias was a significant predictor of bias change, with those who showed a more negative bias preadaptation changing more in a positive direction. Critically, this effect was observed under control but not under stress conditions. These results suggest that the NE/stress system plays an important role in influencing trait-like biases as well as short-term changes in the tendency to perceive ambiguous stimuli as being more rewarding than threatening.

Stress-related laboratory eating behavior in adults with obesity and healthy weight

Stress is an important factor in the progression of irregular eating patterns and has an additional exacerbating impact in people with overweight and obesity. Therefore, in this study, the chewing and food intake was observed after standardized acute stress induction, as well as resting, in people with obesity and healthy weight controls. Twenty-eight women and men with obesity (BMI: 32.76 ± 2.25 kg/m2) were matched with regard to sex and age to 28 people with healthy weight (BMI: 22.58 ± 2.04 kg/m2). After two conditions (Trier Social Stress Test vs. resting condition) the chewing frequency and food intake were measured during a standardized laboratory meal on two separate days. Additionally, for manipulation check of stress induction salivary cortisol and two appraisal questionnaires (Primary Appraisal Secondary Appraisal, Visual Analogue Scale) were used. People with obesity showed after stress and resting condition a lower chewing frequency in contrast to healthy weight controls (F(1, 54) = 12.816, p ≤ .001). Thereby, both groups demonstrated a higher chewing frequency after the stress induction than after the resting condition (F(1, 54) = 7.436, p ≤ .01). There was no difference between the healthy weight controls and the people with obesity in food intake. In conclusion, the present data indicate a possible ‘obese eating style’ with regard to chewing performance. Furthermore, the demonstrated higher chewing frequency after stress induction, in people with obesity and people with healthy weight, might be a stress reduction strategy.

Pilot for novel context generalization paradigm

Background and objectivesFollowing an aversive experience, fears often generalize across contexts. Contextual fear generalization is modeled in a laboratory paradigm in which one context (CTX+) is paired with an aversive unconditional stimulus (US), while the other context (CTX-) is not. The current study sought to validate a novel paradigm assessing contextual fear generalization, and to determine the extent to which stress and anxiety symptoms enhanced contextual fear generalization. MethodsFifty-nine participants were randomized to a stress induction or control arithmetic test, followed by a differential context fear conditioning paradigm. One to three days later, participants completed a generalization gradient test with CTX+, CTX, and four generalization contexts. ResultsWe found successful contextual fear conditioning on measures of US expectancy, self-report fear and valence, and startle reflex, and linear generalization across the contextual gradient on expectancies and self-report measures. Acute stress induction impaired learning of the US-CTX + association during context fear acquisition. Anxiety significantly predicted greater contextual fear generalization as measured by US expectancy. LimitationsOur study provides pilot data introducing a novel fear conditioning paradigm to assess contextual generalization of fear. There is a need for further replication to validate its utility. ConclusionsFindings suggest that individuals high in anxiety show greater contextual fear generalization as measured by US expectancy. Results are discussed in terms of potential mechanisms that contribute to pervasive anxiety.

Small interfering RNA based knock down of acute heat shock and or GGA inducible bovine heat shock protein 70 may interfere invitro expression pattern of TLR2/4 and NOD1/2

Heat shock protein 70 (Hsp70) is a widely known mammalian stress-inducible protein critical for cytoprotection against different stressors. Despite the chaperone based cytoprotective functions, intracellular Hsp70 also participates in diverse immune modulatory activities. To investigate the immune modulatory effect of inducible bovine Hsp70, we examined the expression profile of four major pattern recognition receptors (PRRs) viz. TLR2/4 and NOD1/2 using two different invitro cell cultured models. We observed that, invitro acute heat stress and Geranylgeranylacetone (GGA) induction increased the level of Hsp70 which upregulated the expression of all the four PRRs in both the cell cultured models. However, the expression level of TLR4 was found to be highest followed by NOD2, TLR2 and NOD1. Conversely, specific siRNA based knockdown of Hsp70 showed a decreased expression level of all the four PRRs. This study may add some references pertaining to the innate immune modulatory effects of bovine heat shock protein 70.

Impact of early life adversity on the stress biobehavioral response during nicotine withdrawal

Exposure to early life adversity (ELA) is associated with increased subsequent risk for addiction and relapse. We examined changes in psychobiological responses to stress in dependent smokers and nonsmoking controls and evaluated how history of early adversity may exacerbate acute changes during nicotine withdrawal and acute stress. Smokers were randomly assigned to one of two conditions; 24 h withdrawal (66 smokers) from smoking and all nicotine-containing products or smoking ad libitum (46 smokers) prior to an acute laboratory stress induction session; and 44 nonsmokers provided normal referencing. The laboratory session included a baseline rest, stress and recovery periods. Plasma and saliva samples for the measurement stress hormones and cardiovascular and self-report mood measures were collected multiple times during the session. Multivariate analysis confirmed that all groups showed stress-related increases in negative mood, cardiovascular measures and stress hormones, particularly smokers in the withdrawal condition. Individuals with high ELA showed greater adrenocorticotropic hormone (ACTH), but lower plasma and salivary cortisol levels, than those with low ELA. Cortisol differences were abolished during tobacco withdrawal. These findings demonstrate that ELA moderates the effects of withdrawal on stress-related biobehavioral changes.

Protein phosphatase 2A stimulates activation of TFEB and TFE3 transcription factors in response to oxidative stress

Adaptations and responses to stress conditions are fundamental processes that all cells must accomplish to maintain or restore cellular homeostasis. Cells have a plethora of response pathways to mitigate the effect of different environmental stressors. The transcriptional regulators transcription factor EB (TFEB) and transcription factor binding to IGHM enhancer 3 (TFE3) play a key role in the control of these stress pathways. Therefore, understanding their regulation under different stress conditions is of great interest. Here, using a range of human and murine cells, we show that TFEB and TFE3 are activated upon induction of acute oxidative stress by sodium arsenite via an mTOR complex 1 (mTORC1)-independent process. We found that the mechanism of arsenite-stimulated TFEB and TFE3 activation instead involves protein phosphatase 2A (PP2A)-mediated dephosphorylation at Ser-211 and Ser-321, respectively. Depletion of either the catalytic (PPP2CA+B) or regulatory (PPP2R2A/B55α) subunits of PP2A, as well as PP2A inactivation with the specific inhibitor okadaic acid, abolished TFEB and TFE3 activation in response to sodium arsenite. Conversely, PP2A activation by ceramide or the sphingosine-like compound FTY720 was sufficient to induce TFE3 nuclear translocation. MS analysis revealed that PP2A dephosphorylates TFEB at several residues, including Ser-109, Ser-114, Ser-122, and Ser-211, thus facilitating TFEB activation. Overall, this work identifies a critical mechanism that activates TFEB and TFE3 without turning off mTORC1 activity. We propose that this mechanism may enable some cell types such as immune or cancer cells that require simultaneous TFEB/TFE3 and mTORC1 signaling to survive and achieve robust cell growth in stressful environments.

Fear of pain and cortisol reactivity predict the strength of stress‐induced hypoalgesia

BackgroundAcute stress can have an effect on pain sensitivity, yet the direction of the effect – whether it is hypoalgesic or hyperalgesic – is mixed across studies. Moreover, which part of the stress response influences pain sensitivity is still unclear. In the current experimental study, we aim to examine the effect of acute stress on heat pain thresholds and pain tolerance levels in healthy participants, while taking into account individual differences in stress responses.MethodsForty‐two healthy participants were randomly assigned to either a well‐validated stress paradigm: the Maastricht Acute Stress Task (MAST; combining physical and psychological stressors) or to a nonstressful version of the task. Heat pain thresholds and tolerance levels were assessed at three times: prior to the MAST, immediately after the MAST during the presumed sympatho‐adrenal medullary (SAM) response, and 15 min after MAST to cover the presumed hypothalamus–pituitary–adrenal (HPA) axis response. Stress responses were assessed both subjectively and physiologically.ResultsWe observed that the acute stress induction led to increased heat pain thresholds, an effect that was present only in participants showing a cortisol response following stress induction and only in the presumed HPA axis time window. The strength of this hypoalgesic effect was further predicted by the change in cortisol and by fear of pain levels.ConclusionsOur findings indicate that the HPA axis – and not the autonomic – stress response specifically underlies this stress‐induced hypoalgesic effect, having important implications for clinical states with HPA axis dysfunctions.SignificanceThis experimental study shows that an acute stress induction – that combines physical and psychological stressors – increases heat pain thresholds, but not tolerance in healthy participants. Furthermore, the magnitude of this stress‐induced hypoalgesic effect is predicted by cortisol reactivity and fear of pain, revealing specific involvement of the HPA axis stress system and interactions with pain‐related psychosocial aspects.

Ectopic expression of S28A-mutated Histone H3 modulates longevity, stress resistance and cardiac function in Drosophila

Histone H3 serine 28 (H3S28) phosphorylation and de-repression of polycomb repressive complex (PRC)-mediated gene regulation is linked to stress conditions in mitotic and post-mitotic cells. To better understand the role of H3S28 phosphorylation in vivo, we studied a Drosophila strain with ectopic expression of constitutively-activated H3S28A, which prevents PRC2 binding at H3S28, thus mimicking H3S28 phosphorylation. H3S28A mutants showed prolonged life span and improved resistance against starvation and paraquat-induced oxidative stress. Morphological and functional analysis of heart tubes revealed smaller luminal areas and thicker walls accompanied by moderately improved cardiac function after acute stress induction. Whole-exome deep gene-sequencing from isolated heart tubes revealed phenotype-corresponding changes in longevity-promoting and myotropic genes. We also found changes in genes controlling mitochondrial biogenesis and respiration. Analysis of mitochondrial respiration from whole flies revealed improved efficacy of ATP production with reduced electron transport-chain activity. Finally, we analyzed posttranslational modification of H3S28 in an experimental heart failure model and observed increased H3S28 phosphorylation levels in HF hearts. Our data establish a critical role of H3S28 phosphorylation in vivo for life span, stress resistance, cardiac and mitochondrial function in Drosophila. These findings may pave the way for H3S28 phosphorylation as a putative target to treat stress-related disorders such as heart failure.