Neurobiology of Stress最新文献

{"title":"Increased salivary oxytocin correlates with lower self-reported interoceptive accuracy in functional neurological disorders","authors":"Natascha Stoffel ,&nbsp;Laure von der Weid ,&nbsp;Josef Gross ,&nbsp;Cristina Concetti ,&nbsp;Rupert Bruckmaier ,&nbsp;Selma Aybek","doi":"10.1016/j.ynstr.2025.100765","DOIUrl":"10.1016/j.ynstr.2025.100765","url":null,"abstract":"<div><h3>Introduction</h3><div>Functional Neurological Disorder (FND) is shaped by psychosocial stress, early adversity, and neuroendocrine dysregulation. Oxytocin (OXT), a hormone central to stress regulation and interoception, remains largely unexplored in FND.</div></div><div><h3>Methods</h3><div>In this cross-sectional study, salivary OXT was assessed at four timepoints across 87 participants (42 FND and 45 sex-age-matched healthy controls), including appetite and satiety and hormonal factors (intake of hormonal contraception or menstrual cycle phases) as covariates. Self-reported interoception, attachment style, childhood trauma and sexual functioning were assessed allowing analysis for association.</div></div><div><h3>Results</h3><div>Patients with FND exhibited higher OXT concentrations (averaged across four timepoints: d = 0.55, p = 0.031), which remained when controlling for covariates. Appetite and satiety specifically modulated OXT levels at different timepoints, underlying the group difference after lunch (p = 0.006) and at the end of the study visit (p = 0.035). Self-reported interoceptive accuracy was negatively correlated with OXT (r = −0.31, p = 0.014) and insecure attachment was positively correlated with OXT in controls (r = 0.42, p = 0.005), but not in FND. No associations of OXT and childhood trauma or sexual functioning reports were found.</div></div><div><h3>Discussion</h3><div>The elevated salivary OXT levels observed in patients with FND may reflect a dysregulated or compensatory neuroendocrine response. The combination of higher OXT and lower self-reported interoceptive accuracy suggests that OXT may be upregulated as an attempt to modulate bodily stress or restore homeostatic balance. The absent association of OXT with attachment style in FND specifically supports its role in dealing with socio-affiliative stress.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100765"},"PeriodicalIF":3.6,"publicationDate":"2025-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic state shapes cortisol reactivity to acute stress: A systematic review and meta-analysis of metabolic and hormonal modulators","authors":"Madeleine Kördel ,&nbsp;Maria Meier ,&nbsp;Anne Kühnel ,&nbsp;Nils B. Kroemer","doi":"10.1016/j.ynstr.2025.100764","DOIUrl":"10.1016/j.ynstr.2025.100764","url":null,"abstract":"<div><div>Individual variability in cortisol stress responses is shaped by multiple physiological factors. Yet the interaction with metabolic and hormonal states remains poorly understood. Therefore, we conducted a systematic review and meta-analysis to examine how metabolic factors (particularly glucose) and sex hormone levels (progesterone and estradiol) influence cortisol reactivity to acute stress. We identified 21 studies (<em>N</em> = 1216 participants) and conducted random-effects meta-analyses for metabolic and hormonal states. Across studies, glucose administration was associated with a significant increase in cortisol responses to acute stress compared to fasting or non-glucose control conditions (<em>d</em> = 0.30, 95 % CI = [0.05, 0.60], BF₁₀ = 2.42, NNT = 10.63). In contrast, the effects of sex hormones on cortisol responses were smaller and more variable, with both progesterone and estradiol showing weak and inconsistent associations. Our results highlight a robust modulatory role of metabolic state, specifically glucose availability, on HPA axis reactivity, while evidence for sex hormone effects remains inconclusive. Future research should focus on better harmonization of designs concerning sex hormones and systematically examine interactions between metabolic and hormonal states to better explain sex differences in the prevalences of metabolic and stress-related disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100764"},"PeriodicalIF":3.6,"publicationDate":"2025-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Potential vulnerability and resilience to accelerated brain aging in women exposed to stressful life events: insights from the brain age prediction model","authors":"Hyeonseok Jeong ,&nbsp;Yoonji Joo ,&nbsp;Youngeun Shim ,&nbsp;Yejin Kim ,&nbsp;Hyeonji Lee ,&nbsp;Yunjung Jin ,&nbsp;Seog Ju Kim ,&nbsp;Sujung Yoon ,&nbsp;In Kyoon Lyoo","doi":"10.1016/j.ynstr.2025.100763","DOIUrl":"10.1016/j.ynstr.2025.100763","url":null,"abstract":"<div><div>Brain age prediction models consistently reveal accelerated brain aging in psychiatric disorders, yet associations with stress, independent of formal psychiatric diagnoses, remain uncertain. This study investigated the relationships of emotional and alcohol-use symptoms, common and often comorbid stress-related symptoms, and resilience with brain aging using high-resolution structural MRI data from 520 women who experienced stressful life events. Participants were divided into four groups based on the presence of emotional and alcohol-use symptoms: no symptoms (n = 287), emotional symptoms only (n = 93), alcohol-use symptoms only (n = 79), or both symptoms (n = 61). Individual brain age gap (BAG)—the difference between predicted brain age and chronological age—was calculated using a deep learning-based brain age prediction model. Individual and interactive associations of the presence of two symptoms with BAG were assessed using two-way ANCOVA. Relationships of a continuous composite symptom score integrating both symptoms and resilience with BAG were evaluated. Participants with both symptoms exhibited significantly larger BAG than the other groups, with a statistically significant interaction between two symptom domains (p = 0.017). Across the full sample, composite symptom scores were positively associated with BAG (β = 0.16, p = 0.004), with an even stronger association within individuals with both symptoms (β = 0.34, p &lt; 0.001). Conversely, higher resilience was linked to smaller BAG across all participants (β = −0.10, p = 0.046). The negative association between resilience and BAG was statistically mediated by the composite symptom score (b = −0.011, p = 0.010). These findings may suggest a synergistic, more-than-additive association between stress-related symptoms and accelerated brain aging, as well as a potentially buffering association of resilience.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100763"},"PeriodicalIF":3.6,"publicationDate":"2025-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145156205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FKBP5/FKBP51-mediated signaling pathways in neuropsychiatric diseases: Insights for biomarker development and targeted therapies","authors":"Yinglong Liu,&nbsp;Jiahe Lian,&nbsp;Youli Fu,&nbsp;Shishan Wang,&nbsp;Yongxin Liu,&nbsp;Rui Zhang,&nbsp;Huirong Han","doi":"10.1016/j.ynstr.2025.100762","DOIUrl":"10.1016/j.ynstr.2025.100762","url":null,"abstract":"<div><div>The FK506-binding protein 5 gene encodes FKBP51, a molecular chaperone linked to the pathogenesis of neuropsychiatric diseases. Recent evidence shows that FKBP51 modulates activity of the HPA axis and GR-mediated feedback via dynamic interactions with GR, thereby influencing stress adaptation, inflammatory responses, and neuronal survival. This review systematically analyzes the mechanisms by which <em>FKBP5</em> (and its encoded FKBP51) contributes to neuropsychiatric diseases and identifies shared pathways across these conditions. We further highlight key factors mediating disease variability and susceptibility: sex-, region-, and cell type-specific expression patterns of <em>FKBP5</em>/FKBP51, their temporal dynamics, genetic variants, epigenetic regulation, and gene–environment interactions. Additionally, we propose a “biphasic stress-response model” to conceptualize the temporal dynamics of <em>FKBP5</em>/FKBP51 expression during disease progression. Finally, we explore the translational potential of targeting FKBP51 signaling, and outline pharmacological strategies to modulate chaperone-dependent protein folding and stress pathways as novel therapeutic interventions.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100762"},"PeriodicalIF":3.6,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exposure to early-life stress uncovers shared biological signatures underlying vulnerability in the habenula and insular cortex of male and female adult rats","authors":"Valentina Zonca ,&nbsp;Moira Marizzoni ,&nbsp;Samantha Saleri ,&nbsp;Monica Mazzelli ,&nbsp;Giulia Petrillo ,&nbsp;Maria Grazia Di Benedetto ,&nbsp;Floriana De Cillis ,&nbsp;Marco Andrea Riva ,&nbsp;Annamaria Cattaneo","doi":"10.1016/j.ynstr.2025.100761","DOIUrl":"10.1016/j.ynstr.2025.100761","url":null,"abstract":"<div><div>Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioural phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100761"},"PeriodicalIF":3.6,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145119557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression of Cldn5","authors":"Zhao-Xin Sun ,&nbsp;Mao-Yang Zhou ,&nbsp;Jin-Shan Li ,&nbsp;Yun Zhao ,&nbsp;Fang Xie ,&nbsp;Xue Wang ,&nbsp;Hong Feng ,&nbsp;Zhao-Wei Sun ,&nbsp;Ling-Jia Qian","doi":"10.1016/j.ynstr.2025.100758","DOIUrl":"10.1016/j.ynstr.2025.100758","url":null,"abstract":"<div><div>Chronic stress-induced blood-brain barrier (BBB) dysfunction contributes to neurological disorders, with homocysteine (HCY) as a key risk factor. Considering pharmacotherapy limitations, non-invasive interventions like high-intensity interval training (HIIT) are promising. To determine whether HIIT improves stress-induced BBB dysfunction and cognitive impairment, we first established a chronic unpredictable mild stress (CUMS) model and assigned mice into four groups: Control (Ctrl), CUMS, HIIT, and HIIT + CUMS. Here, we found that HIIT significantly ameliorated cognitive impairment in male CUMS mice, as evidenced by reduced escape latency in morris water maze and increased memory performance in novel object recognition test. HIIT also preserved BBB integrity by ameliorating the tight junction disruption and BBB hyper-permeability in stressed mice. Subsequently, to clarify the role of HCY in the HIIT-mediated effects, we established an HHCY model and divided mice into four groups: Ctrl, HIIT, HHCY, and HIIT + HHCY. The results showed that HIIT normalized the plasma and hippocampal HCY levels by restoring the expression of related metabolic enzymes including CBS, MTHFR and MS, and alleviated HHCY-induced cognitive decline and BBB damage. Further, HIIT reversed HCY-induced Claudin-5 downregulation by inhibiting H3K27me3 enrichment at the Cldn5 (the encoding gene of Claudin-5) promoter region. In addition, HIIT restored the expression of ETS1, one of the transcriptional activators of Cldn5, to facilitate the transcription of Cldn5 gene and the stabilization of BBB. Collectively, these findings reveal that HIIT improves chronic stress-induced cognitive impairment via eliminating the disruptive effects of HHCY on the BBB integrity, offering a non-pharmacological intervention potential for stress-related cognitive deficits.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100758"},"PeriodicalIF":3.6,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Virtual stress testing: Analyzing endocrine, metabolic, cardiovascular, and psychological responses to the TSST-VR","authors":"Eva Fellinger ,&nbsp;Tom Brandt ,&nbsp;Andrea Schittenhelm ,&nbsp;Eric Quarg ,&nbsp;Matthias Pröll ,&nbsp;Gregor Domes ,&nbsp;Annette Schmidt","doi":"10.1016/j.ynstr.2025.100760","DOIUrl":"10.1016/j.ynstr.2025.100760","url":null,"abstract":"<div><h3>Background</h3><div>The Trier Social Stress Test (TSST) is a widely used tool for inducing and measuring stress responses in a controlled environment. In this study, we aimed to explore the effectiveness of a virtual TSST (TSST-VR) in eliciting stress responses across multiple physiological and psychological markers.</div></div><div><h3>Methods</h3><div>A sample of 24 participants underwent the TSST-VR, during which salivary cortisol, alpha-amylase (AA), blood glucose levels, heart rate (HR), root mean square of successive differences (RMSSD) as a measure of heart rate variability (HRV), and subjective stress ratings (NRS) were collected at multiple time points.</div></div><div><h3>Results</h3><div>In a baseline-to-peak analysis, significant increases were observed in HR (M_Diff = 13.04, 95 %-CI [8.19–17.90], p &lt; .001), RMSSD (M_Diff = 17.75, 95 %-CI [3.28–32.22], p &lt; .001), AA (p &lt; .001, r = 1.07), and NRS (p &lt; .001, r = 1.31) measures following the TSST-VR. While no significant changes in cortisol levels were found in the baseline-to-peak analysis across all participants, a secondary cluster analysis identified distinct cortisol responders (baseline-to-peak rise &gt;1.5 mmol/l). Within this group, high cortisol responders (HCR) showed significantly higher cortisol (Wald χ²(7) = 118.03, p &lt; .001), HR (Wald χ²(8) = 17.91, p = .022), and AA levels (Wald χ²(7) = 17.13, p = .017) compared to low cortisol responders (LCR). Area-under-the-curve analysis further confirmed a more robust cortisol stress response in HCR.</div></div><div><h3>Conclusion</h3><div>These findings suggest that the TSST-VR can effectively induce measurable stress responses and may provide insights into individual differences in physiological and metabolic stress reactions. The study highlights the potential of virtual stress paradigms in stress research and underscores the advantages of a virtual setting in terms of standardization and economic considerations.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100760"},"PeriodicalIF":3.6,"publicationDate":"2025-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145057059","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Default mode network connectivity contributes the augment effect stress recovery by natural viewing","authors":"Zini Chen ,&nbsp;Chanyu Wang ,&nbsp;Timothea Toulopoulou ,&nbsp;Xiayan Chen ,&nbsp;Lijing Niu ,&nbsp;Haowei Dai ,&nbsp;Qingzi Zhu ,&nbsp;Yuanyuan Zeng ,&nbsp;Ruibin Zhang","doi":"10.1016/j.ynstr.2025.100759","DOIUrl":"10.1016/j.ynstr.2025.100759","url":null,"abstract":"<div><div>The psychological benefits of exposure to natural environments are well established. However, whether simply viewing nature images produce similar restorative effects and the brain mechanisms involved remain unclear. For study purposes, we recruited 131 healthy university students and randomly assigned them to a nature image viewing group (NG) or a city image viewing group (CG), with 49 participants further selected (NG = 26, CG = 23) to undergo functional magnetic resonance imaging while performing behavioral tasks. First, we compared changes in subjective ratings and salivary cortisol levels, related to affect and stress between the NG and CG after stress induction and image viewing. Next, we examined differences in functional connectivity (FC) patterns of the default mode network (DMN) between the groups during image viewing. Finally, we explored correlations between the recovery effects observed after viewing nature images, along with alterations in FC. Under stress, NG participants reported greater changes in subjective ratings of positive affect (<em>t</em> = 2.610, <em>p</em> = 0.010), lower negative affect (<em>t</em> = −3.008, <em>p</em> = 0.003), and less state rumination (<em>t</em> = −2.103, <em>p</em> = 0.037). Neural data also suggest that connectivity of the DMN subsystems with attentional and executive regions plays a crucial role in modulating stress-related responses during natural experiences. Increased FC between the medial DMN subsystem and other networks was significantly correlated with behavioral recovery scores for both affect and state rumination. These findings indicate that viewing images of natural scenes can aid in stress recovery, highlighting the potential for indoor nature viewing to help mitigate psychological challenges faced in urban environments.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100759"},"PeriodicalIF":3.6,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100088","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From intracellular sensors to systemic resilience: Reframing the biology of stress","authors":"Jakob Hartmann","doi":"10.1016/j.ynstr.2025.100755","DOIUrl":"10.1016/j.ynstr.2025.100755","url":null,"abstract":"<div><div>The biological consequences of chronic stress and trauma are complex, influencing multiple systems and contributing to the development of psychiatric disorders such as MDD and PTSD. Yet, the underlying molecular mechanisms that confer susceptibility in some individuals but resilience in others remain incompletely understood. To help close these knowledge gaps, my work centers on glucocorticoid signaling as a core mechanism underlying stress-related adaptations. This includes the glucocorticoid receptor (GR), its co-chaperones FKBP5 and FKBP4, and regulatory partners such as SKA2. Through a combination of genetic, viral, pharmacological, and transcriptomic approaches, my lab has delineated how these molecules influence HPA axis feedback, fear-related learning, and stress recovery. Recently, we identified a novel, GR-independent role for SKA2 in regulating secretory autophagy, a non-lytic autophagy pathway involved in vesicular cargo release, including cytokine secretion in microglia. These findings established a mechanistic link between intracellular stress signaling and neuroinflammatory responses. In a parallel line of research, we are investigating how chronic stress alters the gut microbiome composition and function, and how these changes impact behavior. Our aim is to harness dietary and probiotic interventions to restore homeostatic balance and enhance stress resilience. By integrating molecular neuroscience with immune and microbiome research, my long-term goal is to build a comprehensive, systems-level model of stress vulnerability and resilience. This approach holds promise for identifying novel biomarkers and therapeutic targets that support mental health and resilience across the lifespan.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"39 ","pages":"Article 100755"},"PeriodicalIF":3.6,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145100034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transcriptomic profiles of susceptibility and resilience to stress in the amygdala and hippocampus of male rats","authors":"Kimberly L.P. Long ,&nbsp;Sandra E. Muroy ,&nbsp;Siamak K. Sorooshyari ,&nbsp;Mee Jung Ko ,&nbsp;Yanabah Jaques ,&nbsp;Kishant Mohan ,&nbsp;Peter Sudmant ,&nbsp;Daniela Kaufer","doi":"10.1016/j.ynstr.2025.100754","DOIUrl":"10.1016/j.ynstr.2025.100754","url":null,"abstract":"<div><div>Traumatic experiences elicit a wide range of cognitive responses in both humans and animals, leading to diverse outcomes such as enhanced performance, cognitive impairment, or the development of mood and anxiety disorders like posttraumatic stress disorder (PTSD). A key challenge in understanding these varied responses is to decipher the underlying biological mechanisms that contribute to individual variability in trauma resilience or susceptibility. The purpose of this study was to elucidate the molecular bases for these differences, focusing on the amygdala and hippocampus—brain regions integral to stress responses. We exposed adult, male rats to an acute, severe stressor and profiled persistent anxiety-like behavior outcomes 7 days later. We investigated the transcriptional signatures in the basolateral amygdala and hippocampal dentate gyrus via bulk RNA sequencing from animals with behavioral outcomes indicative of stress resilience or vulnerability. Our results suggest that the basolateral amygdala and dentate gyrus display distinct transcriptomic changes following acute, severe stress. Furthermore, we identified specific region-dependent genes related to insulin signaling, neural plasticity, and stress responses that correlate with resilient and vulnerable phenotypes. Notably, a larger number of genes separated stress-resilient animals from both control and stress-susceptible animals, underscoring that an active molecular response, particularly in the hippocampus, facilitates protection from the long-term consequences of severe stress. These findings provide novel insight into the mechanisms that engender individual variability in the behavioral responses to stress and offer new targets for the advancement of therapies for stress-induced neuropsychiatric disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"38 ","pages":"Article 100754"},"PeriodicalIF":3.6,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932711","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}