Acute Stress Research Articles

Efficacy of Nigella sativa seed oil against psychophysical stress induced irritable bowel syndrome and anxiety-like symptoms in Wistar rats.

Stressors play a critical role in the progression of irritable bowel syndrome (IBS). Heterogenous stress causes alterations in our bowel movements which can further cause anxiety and depression-like symptoms, decreasing the ability of individuals worldwide to function in social, academic, and employment settings. This study was aimed to investigate the effect of orally administered Nigella sativa (0.2mL/kg b.wt.) seed oil (NSSO) on stress-induced IBS, anxiety, and depression-like symptoms in Wistar rats. In the present study, modelling IBS induced anxiety and depression-like symptoms in rodents have been employed to correlate the pathophysiological mechanisms behind this disorder. Moreover, evaluation of ameliorative potential of traditionally used NSSO in IBS was also carried out. Present investigation indicated that acute stress of 1.5h daily for 20days induced hyper cortisol, gastrointestinal (GI) hypermotility, diarrhoea, altered levels of short chain fatty acids (SCFAs), and inflammation which are common symptoms of IBS. Furthermore, depression and anxiety-like symptoms were validated in test groups by various behavioral tests and decreased levels of 5-HT-Transporter mRNA gene expression, which are clear indicators of cognitive impairment. It is possible that these IBS-like symptoms may have contributed to the pathogenesis of cognitive deficits and depression. However, the anti-oxidative, anti-inflammatory, anti-spasmodic, and possibly the anti-anxiolytic properties of NSSO helped in the mitigation of altered gut-brain axis. Because the concurrent treatment of NSSO alleviated the symptoms of modified GI function and consequently, the anxious & depressive behavior of the animals. Overall, this research explored the protective efficacy of NSSO against stress-induced IBS and depression-like symptoms, shedding light on the potential of this natural compound as a therapeutic option in the field of gastroenterology and psychiatry.

Associative memory cells of encoding fear signals and anxiety are recruited by neuroligin-3-mediated synapse formation

Acute severe stress may induce fear memory and anxiety. Their mechanisms are expectedly revealed to explore therapeutic strategies. We have investigated the recruitment of associative memory cells that encode stress signals to cause fear memory and anxiety by multidisciplinary approaches. In addition to fear memory and anxiety, the social stress by the resident/intruder paradigm leads to synapse interconnections between somatosensory S1-Tr and auditory cortical neurons in intruder mice. These S1-Tr cortical neurons become to receive convergent synapse innervations newly from the auditory cortex and innately from the thalamus as well as encode the stress signals including battle sound and somatic pain, i.e., associative memory neurons. Neuroligin-3 mRNA knockdown in the S1-Tr cortex precludes the recruitment of associative memory neurons and the onset of fear memory and anxiety. The stress-induced recruitment of associative memory cells in sensory cortices for stress-relevant fear memory and anxiety is based on neuroligin-3-mediated new synapse formation.

An experimental investigation into the impact of acute stress on alcohol craving.

Drinking to cope is associated with many negative alcohol-related outcomes among college students, such as increased alcohol use, drinking-related problems, and alcohol use disorders. Previous experimental studies have shown that students exposed to a stressor, compared to those not exposed to a stressor, drink more and have stronger urges to drink, presumably to cope with the stressor. However, no such study has tested this effect using a remote-based stressor, which may be more common for students because of the recent increase in online learning. As such, the present study aimed to (a) test the impact of an acute stressor on state anxiety and alcohol craving and (b) investigate trait-level drinking characteristics as potential moderators of the impact of the acute stressor. Participants were 137 (Mage = 19.9, SDage = 2.0; 82.5% female; 41.6% White) college students who consumed alcohol in the past month. Using a between-subjects experimental design, we assigned participants randomly to an experimental (i.e., acute stress) condition or control (i.e., neutral) condition, and they completed a premanipulation battery of alcohol-related attitudes and behaviors and a postmanipulation measure of alcohol craving. On average, participants in the experimental condition reported greater increases in anxiety than those in the control condition, but there were no differences found in alcohol craving. However, for both anxiety and craving, greater increases from pre- to postmanipulation were found when trait-level anxiety and trait-level drinking were high, respectively. Thus, heavier drinking college students may be at greater risk for craving alcohol in response to stress than those who typically drink less. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Older patients affected by COVID-19: investigating the existence of biological phenotypes

IntroductionCOVID-19 provides an opportunity to examine biological phenotypes (observable morphological, functional and biological characteristics) in individuals who experience the same acute condition, potentially revealing differences in response to acute external stressors. The aim our study was to investigate biological phenotypes in older patients hospitalized for COVID-19, exploiting a panel of aging biomarkers.MethodsData were gathered from the FRACOVID Project, an observational multicenter study, aimed to evaluate the impact of frailty on health-related outcomes in patients 60 + with COVID-19 in Northern Italy. A hierarchical cluster analysis was run using log-transformed and scaled values of TNF-a, IL-1 beta, IL-6, PAI-1, GDF-15, NT-proBNP, and Cystatin C evaluated at admission.ResultsEighty-one participants (mean age 75.3 years; 60.5% male) were evaluated. Frailty was identified in 42% of the sample and 27.2% were unable to ambulate outdoors. The mean hospital stay was 24.7 days, with an in-hospital mortality rate of 18.5%. Three biological phenotypes were found: (1) ‘inflammatory’, with high inflammatory biomarkers; (2) ‘organ dysfunction’, characterized by elevated cystatin C and NT-proBNP, and lower inflammatory markers; and (3) ‘unspecific’, with lower NT-proBNP and GDF-15 levels, and intermediate concentrations of other biomarkers. The ’organ dysfunction’ phenotype showed the highest mean age and prevalence of frailty, disability, and chronic diseases. The ‘inflammatory‘ phenotype showed the highest burden of respiratory and systemic signs and symptoms of infection.ConclusionBiological phenotypes might be used to identify different clinical and functional phenotypes in individuals affected by COVID-19.

Prospective stability of memory for peritraumatic dissociation and anxiety: Replication and extension examining PTSD treatment modality and response.

Retrospective memory for peritraumatic reactions occurring during or immediately after trauma exposure may decrease in intensity for some over treatment. This may be due to psychotherapy-specific memory processes, such as repeated accessing of the trauma memory. Additionally, it may be that recovery drives changes in memory for these experiences. Critical to examining these hypotheses is an effective control treatment that reduces symptoms but does not directly involve repeated retrieval of the trauma memory, such as pharmacotherapy. In a sample of 200 individuals with posttraumatic stress disorder, retrospective memory for dissociation and anxiety occurring around the index traumatic event (Peritraumatic Dissociative Experiences Questionnaire, Marmar et al., 1997; Stanford Acute Stress Reaction Questionnaire, Cardeña et al., 2000) was assessed before and after treatment in a randomized clinical trial (NCT00127673) comparing prolonged exposure and sertraline. Participants reported that their memory for dissociation and anxiety at the time of the trauma was less intense at posttreatment (d = 0.26-0.64). There was no difference between prolonged exposure and sertraline on these memory indices. However, treatment responders, using a clinically meaningful change cutoff score, remembered their reactions at the time of the trauma as less dissociative (d = 0.66) and less anxious (d = 1.19) at posttreatment than nonresponders. Retrospective memory for the intensity of reactions experienced at the time of the traumatic event decreased from pre- to posttreatment, with effects most pronounced for those who made clinically meaningful gains in treatment. Inclusion of a nonpsychotherapy intervention control argues that recovery processes may explain these shifts and point to potential mood-dependent memory effects. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cardiovascular reactivity during conversations about discrimination is buffered by social support among U.S. Latines

Racial discrimination is conceptualized as an acute and chronic stressor. Like other acute stressors, lab-based studies demonstrate acute effects of discrimination-related stressors on stress-related cardiovascular outcomes, including total cardiac output, blood pressure, and indices of sympathetic and parasympathetic nervous system activity. Critically, it is important to understand how individual and social factors buffer the experience of race-related acute stress. The current study extends existing work by measuring cardiovascular indices of stress during conversations about racial/ethnic discrimination and examines the moderating role of social support. Latine/Hispanic participants (N = 97) talked about personal discrimination experiences with either a close other or a research assistant they had never previously met. Participants in both conditions exhibited cardiovascular reactivity indicative of stress during the conversation. Additionally, patterns of reactivity reflected a more adaptive stress response and recovery profile when participants talked about discriminatory experiences with a close other relative to a stranger (less parasympathetic withdrawal during the stressor and more parasympathetic rebound during recovery). These patterns are consistent with a stress buffering account of social support, which suggests social bonds and community-level support are critical to consider in interventions to mitigate the harms of experiencing discrimination and prevent chronic health disparities.

Hematopoietic stem cell metabolism within the bone marrow niche - insights and opportunities.

Hematopoiesis unfolds within the bone marrow niche where hematopoietic stem cells (HSCs) play a central role in continually replenishing blood cells. The hypoxic bone marrow environment imparts peculiar metabolic characteristics to hematopoietic processes. Here, we discuss the internal metabolism of HSCs and describe external influences exerted on HSC metabolism by the bone marrow niche environment. Importantly, we suggest that the metabolic environment and metabolic cues are intertwined with HSC cell fate, and are crucial for hematopoietic processes. Metabolic dysregulation within the bone marrow niche during acute stress, inflammation, and chronic inflammatory conditions can lead to reduced HSC vitality. Additionally, we raise questions regarding metabolic stresses imposed on HSCs during implementation of stem cell protocols such as allo-SCT and gene therapy, and the potential ramifications. Enhancing our comprehension of metabolic influences on HSCs will expand our understanding of pathophysiology in the bone marrow and improve the application of stem cell therapies.

The Impact of Acute Ammonia Nitrogen Stress on the Gill Tissue Structure and Antioxidant Ability of Gills and Red and White Muscle in Juvenile Yellowfin Tuna (Thunnus albacares)

To explore the impacts of acute ammonia nitrogen (NH3-N) stress on gill structure and the antioxidant ability of red and white muscles in juvenile yellowfin tuna (Thunnus albacares), this study used natural seawater as a control, establishing two experimental NH3-N groups at 5 and 10 mg/L. Gills and red and white muscle were taken at 6, 24, and 36 h for the determination of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GHS-PX) levels, and to observe gill structure. The results indicated that, with increasing time, the MDA concentration and CAT activity in the gills of the 5 mg/L group showed a trend of first increasing and then decreasing, while SOD activity exhibited a downward trend. In the 10 mg/L group, MDA concentration showed an increasing trend, while SOD, CAT, and GSH-PX activities demonstrated a trend of first increasing and then decreasing. In the 5 mg/L group, the MDA concentration and GSH-PX activity in the red muscle showed an increasing trend. In the 10 mg/L group, MDA concentration and SOD and CAT activities exhibited a downward trend. In the 5 mg/L group, the MDA concentration and SOD activity in the white muscle showed a downward trend, while CAT activity exhibited an increasing trend. In the 10 mg/L group, MDA concentration and CAT activity demonstrated a trend of first increasing and then decreasing, while SOD activity showed a downward trend. Ammonia nitrogen can lead to necrosis and shedding of gill epithelial cells, cell vacuolation, edema, as well as proliferation, hypertrophy, and fusion of secondary lamellae. This study demonstrates that NH3-N can alter gill structure and reduce the antioxidant ability of gills and red–white muscle. The findings provide scientific data that can support the aquaculture and recirculating aquaculture systems of juvenile tuna.

Behavioural profiling following acute stress uncovers associations with future stress sensitivity and past childhood abuse.

Background: Individuals greatly differ in their responses to acute stress, ranging from resilience to vulnerability that may yield stress-related psychopathology. Stress-related psychopathologies involve, by definition, substantial modifications across multiple behavioural domains, including impaired cognitive, affective and social functioning. Nevertheless, and despite extensive investigation of individual variability in stress responsivity, no study to date simultaneously assessed the impact of acute stress across multiple behavioural domains within a given individual.Objective: To address this critical gap, 84 healthy female participants (mean age 24.45 ± 3.02, range 19-35) underwent an established acute stress induction procedure and completed three behavioural tasks, probing the functional domains of positive, cognitive and social processing, both before and after the acute stress procedure.Method: A novel behavioural profiling algorithm was implemented to identify individuals whose performance was substantially impacted by stress across all three functional domains.Results: Approximately 30% of participants exhibited substantial deviation in their performance from before to after stress in all three tasks, hereon defined as stress-affected. Stress-affected participants did not differ in their psychological and physiological responses to the acute stress procedure from the other stress-unaffected 70% of the sample. However, follow-up assessments in 66 of these participants revealed higher levels of stress six months following the procedure among the stress-affected compared to the stress-unaffected group. Stress-affected individuals also reported more aversive childhood experiences, such that the odds of participants who were sexually abused at an early age to be affected behaviourally by acute stress later in life increased by more than five-fold.Conclusions: Taken together, these findings suggest that being affected by acute stress across multiple functional domains is associated with future stress sensitivity and past childhood sexual abuse. Probing individual differences in the impact of acute stress across domains of functionality may better align with the multi-dimensional nature of stress responsivity, uncovering latent vulnerability.

Olfactory stimulation with multiple odorants prevents stress-induced cognitive and psychological alterations

Abstract Acute and chronic stress markedly affects behavior by triggering sympathetic nervous system activation and several hypothalamus-pituitary-adrenal-dependent responses. Brain regions of the limbic system are responsible for the regulation of stress response, and different reports have demonstrated that their activity can be influenced by olfactory stimuli. Here we report that, in mice exposed to acute restraint stress, olfactory stimulation employing a combination of three odorants, i.e., vanillin, limonene and green odor (trans-2-hexenal and cis-3-hexenol) decreased anxiety behavior, assessed in the elevated plus maze, and halted recognition and spatial memory deficits, as appraised in two different object recognition tasks. Of note, when applied singularly, the same odorants were unable to block the detrimental effects of stress. We also found that the multiple odorants stimulation prevented the development of depressive symptoms assessed by the sucrose splash test and forced swim test in an experimental model of depression, i.e., mice exposed to a chronic unpredictable stress paradigm, and reduced interleukin 1β levels in the prefrontal cortex of depressed mice. Collectively, our data indicate that olfactory stimulation counteracts the detrimental effects of acute and chronic stress on mood regulation and cognitive functions, thus representing a potential tool for the treatment of stress-induced disorders.

Music’s Influence on Cardiovascular Parameters During Cognitive Testing

BackgroundMozart’s music has been found to decrease stress and anxiety by decreasing blood pressure and heart rate in diverse populations. However, the influence on Mozart during cognitive tests remains unclear. Due to its proven anti-stress effects, Mozart’s music may be an effective tool for decreasing cardiovascular parameters during cognitive testing. MethodsThe cognitive test chosen was an untimed pattern-recognition Mensa test. The chosen song was Mozart’s Sonata K448. We included 10 adult participants who met the inclusion criteria. A matched pair study design was incorporated. All participants completed a diagnostic test that assessed relative cardiovascular sensitivities to the acute stress produced by the Mensa test. Participants were matched based on cardiovascular sensitivities, rating of momentary stress, and sex. Pairs were then randomly allocated to take the test again; one took the test while listening to Mozart’s Sonata K448, the other took it in silence. Post-test evaluations were then completed. ResultsIn both groups, the intervention did not induce significant changes in BP or HR, except for a significant decrease in SBP in the no music group (p=0.043). When comparing the difference in relative blood pressure and heart rate changes between the two groups, none were significantly different. There were significant decreases in perceived stress and increases in perceived relaxation in the music group (p=0.024 and p=0.039, respectively). ConclusionOur findings suggest that Mozart’s music does not decrease cardiovascular responses during cognitive testing. Additionally, perceived stress is independent of cardiovascular indicators of stress which has unknown implications.

Comparative transcriptome analysis of low- and high-latitude populations of Charybdis japonica under temperature stress

Global climate change has caused rapid temperature changes in marine environments. Understanding how marine organisms respond to temperature changes can help predict their richness of future biodiversity. In this study, we examined the gene expression levels and the difference in the pathways that are responsive to acute temperature stress in low- and high-latitude populations of the shore swimming crab, Charybdis japonica. The two populations of C. japonica were exposed to low- and high-temperature stresses (15°C and 28°C) and used for transcriptome sequencing. Genetic regulatory ability changes were compared to determine the diverse response of the two crab populations to temperature change. The gene expression levels and functional enrichment analysis showed that the low-latitude crab regulated more genes (938) that were mainly enriched in DNA replication and metabolic pathways, whereas the high-latitude crab regulated less genes (309) that were mainly enriched in genetic information processing at low-temperature stress. Furthermore, the low-latitude crab regulated less genes (33) that were mainly enriched in genetic information processing, whereas the high-latitude crab regulated more genes (280) that were mainly enriched in signal transduction and cellular process at high-temperature stress. These results implied that the low-latitude population was more resilient to high-temperature stress, while the high-latitude population was more resilient to low-temperature stress. This study enhances our understanding of how different geographic C. japonica populations respond to varying temperature environments in their living zone, which could be helpful for predicting future biodiversity trends of intertidal crustaceans under global climate change.

Effects of cold stress on the blood-brain barrier in Plectropomus leopardus

BackgroundThe leopard coral grouper (Plectropomus leopardus) is a commercially valuable tropical marine fish species known to be sensitive to low temperatures. A comprehensive understanding of the molecular mechanisms governing its response to acute cold stress is of great importance. However, there is a relative scarcity of fundamental research on low-temperature tolerance in the leopard coral grouper.MethodsIn this study, a cooling and rewarming experiment was conducted on 6-month-old leopard coral groupers. Within 24 h, we decreased the ambient temperature from 25 °C to 13 °C and subsequently allowed it to naturally return to 25 °C. During this process, a comprehensive investigation of serum hormone levels, enzyme activity, and brain transcriptome analysis was performed.ResultsP. leopardus displayed a noticeable adaptive response to the initial temperature decrease by temporarily reducing its life activities. Our transcriptome analysis revealed that the differentially expressed genes (DEGs) were primarily concentrated in crucial pathways including the blood-brain barrier (BBB), inflammatory response, and coagulation cascade. In situ hybridization of claudin 15a (cldn15a), a key gene for BBB maintaining, further confirmed that exposure to low temperatures led to the disruption of the blood-brain barrier and stimulated a pronounced inflammatory reaction within the brain. Upon rewarming, there was a recovery of BBB integrity accompanied by the persistence of inflammation within the brain tissue.ConclusionsOur study reveals the complex interactions between blood-brain barrier function, inflammation, and recovery in P. leopardus during short-term temperature drops and rewarming. These findings provide valuable insights into the physiological responses of this species under cold stress conditions.

A Prospective Cohort Study on the Effects of Repeated Acute Stress on Cortisol Awakening Response and Immune Function in Military Medical Students

Background: The cortisol awakening response (CAR) is a pivotal component of the body’s stress response, yet its dynamics under repeated acute stress and its interplay with immune biomarkers remain inadequately understood. Methods: This study examined 80 second-year military medical students undergoing a 5-day intensive surgical simulation designed to elicit stress responses. Salivary samples were collected daily upon waking and 30 min thereafter to measure cortisol and a panel of cytokines using bead-based multiplex ELISA. Results: Analysis revealed a significant blunting of the CAR on the third day of training (p = 0.00006), followed by a recovery on the fourth day (p = 0.0005). Concurrently, specific cytokines such as CXCL1 (r = 0.2, p = 0.0005), IL-6 (r = 0.13, p = 0.02), IL-10 (r = 0.14, p = 0.02), and VEGF-A (r = 0.17, p = 0.003) displayed patterns correlating with the CAR, with increased strength of associations observed when assessing cytokine levels against the CAR of the preceding day (CXCL1 r = 0.41, p = 0.0002. IL-6 r = 0.38, p = 0.0006. IL-10 r = 0.3, p = 0.008. VEGF-A r = 0.41, p = 0.0002). Conclusions: These results suggest a temporal relationship between stress-induced cortisol dynamics and immune regulation. The CAR pattern demonstrated in this study may represent induction of and recovery from psychological burnout. Moreover, the observed cytokine associations provide insight into the mechanisms by which stress can influence immune function. The results may have broader implications for managing stress in high-performance environments, such as military and medical professions, and for identifying individuals at risk of stress-related immune suppression.

Dissecting the dynamics of cell death pathways in Hirschsprung’s disease: a comparative analysis of viable and non-viable cells under proinflammatory conditions

PurposeThe present study explores the dynamics of cell death in Hirschsprung’s disease (HSCR) and control (CO) groups under inflammatory stress conditions.MethodsUsing flow cytometry, we analyzed intestinal colonic organoid cultures derived from the ganglionic segment of the HSCR and CO groups. Our analysis focused on the quantification of RIPK1-independent and RIPK1-dependent apoptosis, as well as necroptosis in both viable and non-viable cells under acute and chronic inflammatory stress.ResultsOur findings indicate that HSCR cells are particularly vulnerable to inflammation during acute proinflammatory stress, as evidenced by an increase in dead cells (Zombie +). Under chronic conditions, adaptive changes are observed in both HSCR and CO groups, indicating survival mechanisms. These adaptations are uniquely altered in HSCR, suggesting an impaired response to chronic inflammation. HSCR cells show significantly decreased RIPK1-dependent apoptosis in acute scenarios compared to chronic ones, unlike the CO group, implying varied responses to different inflammatory stresses. In non-viable cells, considerable changes in RIPK1-dependent apoptosis under chronic conditions in HSCR indicate a heightened inflammatory response compared to CO.ConclusionThis research provides insights into cell death regulation in HSCR under inflammatory stress by using patient-derived organoids, underscoring the complexity of its inflammatory response.

Assessing Mental Health During an Extreme Weather Event in Southern Brazil.

This study aimed to evaluate mental health factors in individuals affected by the floods in Rio Grande do Sul from May 10 to June 6, 2024. A real-time survey was conducted with 1,552 participants. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Acute Stress Disorder (ASD) symptom checklist were used to assess mental health outcomes. Sociodemographic factors, trauma exposure, rescue participation, and psychological support were evaluated. Statistical analyses included t-tests, ANOVA, linear regression, and MANCOVA. High rates of depressive and anxious symptoms were found, with over half of the individuals with moderate to severe symptoms reporting no prior history of these conditions. Participants directly affected by the floods, and those with close ones affected, had higher PHQ-9, GAD-7, and ASD scores compared to the unaffected group. Moreover, younger age, female sex, lower family income, participation in rescues, and unmet psychological support needs were correlated with worse mental health outcomes. Individuals who participated in rescues had significantly higher rates of suicide ideation. Notably, psychological support had the largest effect size in mitigating mental health symptoms, regardless of trauma exposure status, when controlled for age, sex, and income according to MANCOVA. The findings highlight the critical role of psychological support in disaster response and the importance of community resilience. Real-time data collection during crises can inform targeted interventions, emphasizing the need for robust mental health services and community support networks. These efforts are essential to reduce long-term psychological morbidity and foster recovery in vulnerable populations.

Rivaroxaban as a protector of Oxidative Stress-induced Vascular Endothelial Glycocalyx Damage via The IQGAP1/PAR1-2/PI3K/Akt Pathway.

The vascular endothelial glycocalyx, crucial for blood vessel integrity and homeostasis, is vulnerable to oxidative stress, leading to endothelial dysfunction, which strongly correlates with cardiovascular disease (CVD). This study investigates the protective effects of rivaroxaban, a FXa inhibitor, on the glycocalyx under oxidative stress condition. We examined the impact of rivaroxaban on human umbilical vein endothelial cells (HUVECs) exposed to acute and chronic H₂O₂-induced oxidative stress. Rivaroxaban dose-dependently suppressed syndecan-1, a key component of the glycocalyx, shedding from cell surface, and enhanced protease-activated receptor (PAR)1-PAR2/ phosphatidylinositol-3-kinase (PI3K)-dependent cell viability after acute induction of H2O2. This protective effect was linked to the translocation of IQGAP1, a scaffold protein that modulates the actin cytoskeleton, to the perinucleus from the cell membrane. Under chronic H2O2 treatments, rivaroxaban improves cell viability accompanied by an increase in hyaluronidase activities, aiding the turnover and remodeling of hyaluronic acid within the glycocalyx. We identify that rivaroxaban protects against oxidative stress-induced endothelial glycocalyx damage and cell viability through IQGAP1/PAR1-2/PI3K/Akt pathway, offering a potential to be a therapeutic target for CVD prevention.

A Neural Circuit For Bergamot Essential Oil-Induced Anxiolytic Effects.

Aromatic essential oils have been shown to relieve anxiety and enhance relaxation, although the neural circuits underlying these effects have remained unknown. Here, it is found that treatment with 1.0% bergamot essential oil (BEO) exerts anxiolytic-like effects through a neural circuit projecting from the anterior olfactory nucleus (AON) to the anterior cingulate cortex (ACC) in acute restraint stress model mice. Collectively, in vivo two-photon calcium imaging, viral tracing, and whole-cell patch clamp recordings show that inhalation exposure to 1.0% BEO can activate glutamatergic projections from the AON to GABAergic neurons in the ACC, which drives inhibition of local glutamatergic neurons (AONGlu→ACCGABA→Glu). Optogenetic or chemogenetic manipulation of this pathway can recapitulate or abolish the BEO-induced anxiolytic-like behavioral effects in mice with ARS. Beyond depicting a previously unrecognized pathway involved in stress response, this study provides a circuit mechanism for the effects of BEO and suggests a potential target for anxiety treatment.

Stress-induced cortisol response predicts empathy for pain: The role of task-based connectivity between the insula and sensorimotor cortex during acute stress

Empathy for pain is a key driver of prosocial behavior and is influenced by acute psychosocial stress. However, the role of task-based brain connectivity during acute stress have been neglected. Hence, we aimed to explore the relationship between the magnitude of cortisol response to acute stress and empathy for pain, as well as the neural connectivity mechanisms involved. In this study, 80 healthy participants (37 women and 43 men) were exposed to the acute psychosocial stress paradigm (ScanSTRESS) and were scanned by functional magnetic resonance imaging. Saliva samples were collected to measure the magnitude of cortisol stress response. Subsequently, the participants took part in a pain-video task to assess their empathy for pain. Six participants were excluded because of physical discomfort or excessive head movement in all runs during the task-dependent fMRI scan. Therefore, 33 women and 41 men were included in data analysis. We found that empathy for pain was negatively correlated with the magnitude of cortisol stress response (r = -0.268, p = 0.018) and that the task-based connectivity between the salience network and sensorimotor network, including its sub-network and sub-region, was negatively correlated with the magnitude of cortisol stress response, and positively correlated with empathy for pain. Furthermore, task-based connectivity between the insula and the paracentral lobule mediates the effect of the stress-induced cortisol response on empathy for pain (indirect effect = -0.0152, 95% CI = [- 0.036, -0.001], p = 0.036). Our research suggests that empathy is not only correlated with stress-induced glucocorticoids but also tied to the stress-induced reduced communication between basic and higher brain regions.

Transcriptome dynamics in mouse amygdala under acute and chronic stress revealed by thiol-labeled RNA sequencing

Both acute and chronic stress have significant impact on brain functions. The amygdala is essential in mediating stress responses, but how its transcriptomic dynamics change under stress remains elusive. To overcome the difficulties in detecting subtle stress-induced changes by evaluating total RNA using classic RNA sequencing, we conducted thiol-labeled RNA sequencing (SLAM-seq). We injected 4-thiouridine (4sU) into mouse amygdala followed by SLAM-seq to detect nascent mRNA induced by acute and chronic restraint stress, and found that SLAM-seq could label actively transcribed genes in the major neuronal and glial subtypes. Using SLAM-seq, we found that chronic stress led to higher turnover of a group of genes associated with myelination, and this finding is confirmed by immunostaining which showed increased myelination in the chronically stressed amygdala. Additionally, genes detected by SLAM-seq and RNA-seq only partially overlapped, suggesting that SLAM-seq and RNA-seq are complementary in identifying stress-responsive genes. By applying SLAM-seq in vivo, we obtained a rich dataset of genes with higher turnover in the amygdala under stress.