Neurobiology of Stress最新文献

{"title":"Editorial: Expanding horizons in stress research—innovative paradigms and new directions in 2025","authors":"Mathias V. Schmidt , Lawrence Reagan","doi":"10.1016/j.ynstr.2026.100803","DOIUrl":"10.1016/j.ynstr.2026.100803","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"42 ","pages":"Article 100803"},"PeriodicalIF":3.6,"publicationDate":"2026-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148231435","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":"The adrenal is doing what it’s supposed to do, you just don't understand it","authors":"Christina Y. Cantave,&nbsp;Megan Gunnar","doi":"10.1016/j.ynstr.2026.100792","DOIUrl":"10.1016/j.ynstr.2026.100792","url":null,"abstract":"<div><div>Exposure to early life adversity is thought to induce long-term alterations in the hypothalamic-pituitary-adrenal (HPA) axis activity and regulation, particularly when such experiences occur during periods of rapid neurodevelopment in early childhood. Although this hypothesis is well supported in animal research, evidence in humans remains comparatively limited and less well understood. The present review synthesizes current evidence on the immediate and long-term impact of adversity experienced roughly in the first 5 years of life, focusing on two forms of severe adverse caregiving: early institutional care and child maltreatment. Across studies, children exposed to early adverse care show persistent alterations in HPA axis activity under both basal and stress-related conditions, extending from infancy to adulthood. We examine how the developmental timing, duration and severity of exposure, as well as the caregiving context, affect these outcomes, and highlight emerging evidence of potential recalibration of the HPA axis during puberty following marked changes (for good or bad) in caregiving quality. We conclude by outlining the implications of this body of work for understanding the programming effects of early adversity and by identifying key methodological limitations and priorities for future research. In particular, longitudinal designs with repeated assessments, combined with integrative multisystem resilience-oriented approaches, are essential. This should be integrated with and neurobiological grounded by, mechanistic animal studies. Together, these efforts will help elucidate how and when early adversity becomes biologically embedded across child development.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100792"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399975","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":"Decoding the cellular landscape of biological stress in the human brain","authors":"Natalie Matosin","doi":"10.1016/j.ynstr.2026.100782","DOIUrl":"10.1016/j.ynstr.2026.100782","url":null,"abstract":"<div><div>Adversity exposure leading to a dysfunctional biological stress response represents a significant risk factor underlying psychiatric disorder aetiology for many individuals. Yet our understanding of how different cell types within stress-responsive brain circuits differentially contribute to psychiatric risk remains limited, particularly in the human brain. Our lab, the Mental Illness, Neurobiology and Disorders of Stress (MINDS) Laboratory, has been addressing this knowledge gap through large-scale analyses of postmortem human brain specimens from individuals with major psychiatric disorders who experienced high levels of adversity in their lives. We have a focus on examining targets and pathways involved in HPA axis and glucocorticoid-mediated signalling in the human brain at single-cell resolution. Through integration of single-cell and spatial molecular data with advanced histological approaches to evaluate cellular morphology, we have identified cell-type-specific vulnerability patterns to the biological consequences of adversity exposure. Our findings demonstrate how different populations respond to adversity through coordinated molecular and morphological changes that affect synaptic function and stability. This approach exemplifies the potential for combining new spatial omics and traditional histological approaches to achieve precision medicine in psychiatry, by revealing specific cellular targets for therapeutic intervention. Our work facilitates a shift from broad neurotransmitter-based interventions towards targeted therapeutic strategies for stress-related psychiatric disorders. These advances provide a foundation for developing more effective treatments tailored to the underlying cellular pathology in individual patients with stress-related mental illness.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100782"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146049006","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":"Central medial and paraventricular thalamic afferents to the orbitofrontal cortex have differential effects on reversal learning","authors":"Kathleen M. Tuite ,&nbsp;Megan C. Ouellette ,&nbsp;Milena Girotti ,&nbsp;David A. Morilak","doi":"10.1016/j.ynstr.2026.100789","DOIUrl":"10.1016/j.ynstr.2026.100789","url":null,"abstract":"<div><div>Cognitive impairments are prominent in stress-related psychiatric disorders, such as depression and PTSD. While current therapies may improve mood symptoms, many patients experience persistent deficits in cognitive flexibility. One form of cognitive flexibility disrupted in such conditions is reversal learning, dependent on the orbitofrontal cortex (OFC). Chronic stress causes OFC dysfunction and reversal learning deficits. However, the circuit mechanisms by which this happens are not understood. We hypothesized that two thalamic afferents to the OFC, the central medial (CM) and paraventricular thalamus (PVT), contribute to successful reversal learning and the detrimental effects of stress, respectively. We showed a decrease in activation of lateral OFC, measured by Fos induction, following reversal learning, and increased activation of both CM and PVT. Chronic unpredictable stress (CUS) impaired reversal learning and increased ΔFosB expression in CM and PVT projections to the OFC. Next, we chemogenetically manipulated each pathway to the OFC in non-stressed and stressed rats. Inhibition of the CM to OFC pathway in non-stressed rats disrupted reversal learning, while activation of this pathway restored reversal learning in stressed rats. By contrast, activation of the PVT to OFC pathway disrupted reversal learning in non-stressed male rats. In stressed males, inhibition of the PVT to OFC pathway ameliorated the detrimental effects of CUS. Effects of PVT to OFC manipulations were absent in females. These results indicate that the CM-OFC pathway promotes successful reversal learning in both sexes, and the PVT-OFC pathway contributes to the detrimental effects of stress on reversal learning in a sex-dependent manner.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100789"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399522","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":"Corticotropin releasing hormone-expressing inputs to the thalamic paraventricular nucleus: pathways from mother to memory?","authors":"Jorge M. Mendoza ,&nbsp;Amalia Floriou-Servou ,&nbsp;Yuncai Chen ,&nbsp;Cassandra Kooiker ,&nbsp;Mason Hardy ,&nbsp;Tallie Z. Baram","doi":"10.1016/j.ynstr.2026.100794","DOIUrl":"10.1016/j.ynstr.2026.100794","url":null,"abstract":"<div><div>Thalamic paraventricular nucleus (PVT) neurons expressing the corticotropin releasing hormone receptor 1 (CRHR1) are preferentially activated during early life stress. However, it is unclear how the receptor ligand, the stress-related peptide CRH, reaches receptor-bearing cells. To address this question, we mapped local, proximal and distal sources of CRH, i.e., CRH expressing neurons within, adjacent to and projecting to PVT. The combined use of retrograde and anterograde viral-genetic tracing approaches, validated with immunohistochemistry, identified an array of CRH neurons within PVT, in the adjacent paratenial nucleus as well as projecting to PVT from the parabrachial and Barrington nuclei. The latter are poised to convey to the PVT sensory signals from maternal grooming, as envisioned by Seymour Levine in the 1950s.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100794"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399884","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":"Behavioral phenotype analysis highlights sleep heterogeneity and brain cellular activations in a mouse model of PTSD","authors":"Emma Lardant ,&nbsp;Otilia Kelemen ,&nbsp;Louise Pialoux ,&nbsp;Coline Gervy ,&nbsp;Blake Rea ,&nbsp;Betty Poly ,&nbsp;Damien Claverie ,&nbsp;Frederic Chauveau","doi":"10.1016/j.ynstr.2026.100787","DOIUrl":"10.1016/j.ynstr.2026.100787","url":null,"abstract":"<div><div>Exposure to intense and unavoidable stressor can lead to Post Traumatic Stress Disorder (PTSD) in some individuals. The heterogeneity of symptom expression, including sleep alterations, may explain the high rate of both non-responder and relapse of current treatments. Understanding individual-specific brain activity related to stress behavioral responses seems crucial for developing refined and personalized treatments strategies.</div><div>For this purpose, we evaluated the behavior of outbred mice through multiple tests up to 28 days after two inescapable electrical foot-shocks (FS). A two-step behavioral phenotype analysis successfully identified three phenotypes among FS mice. First, the scoring of behavioral alterations severity, based on PTSD-like symptoms, differentiated susceptible and resilient animals. Second, the specific type of stress-induced defensive behaviors further categorized two susceptible phenotypes: freezers and escapers.</div><div>Sleep patterns specific to phenotype emerged 14 days after the FS exposure. Notably, resilient mice exhibited more time spent in rapid eye movement sleep than susceptible animals, a variable that was negatively correlated to the behavioral alteration severity score.</div><div>Finally, behavioral profiling highlighted different c-Fos protein expressions in amygdala (AMG) and in the periaqueductal gray matter (PAG) across phenotypes, suggesting region-specific neural responses. Specifically, the severity of PTSD-like behaviors was correlated to the right lateral and central-lateral AMG cellular activations.</div><div>In conclusion, this study emphasizes the relevance of using composite score of multiple behavioral tests to better understand the complexity of stress responses and interindividual variability. Moreover, our findings suggest a role of REM sleep in promoting behavioral resilience to high-intensity stress.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100787"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399521","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":"Impact of adverse postnatal environment on emotional regulation and neuroimmune function in adolescent rats prenatally exposed to alcohol","authors":"Parker J. Holman ,&nbsp;Victoria R. Vella ,&nbsp;Samantha L. Baglot ,&nbsp;Dylan Yeates ,&nbsp;Pushpkiran Ubi ,&nbsp;Joanne Weinberg ,&nbsp;Tamara S. Bodnar ,&nbsp;Charlis Raineki","doi":"10.1016/j.ynstr.2026.100793","DOIUrl":"10.1016/j.ynstr.2026.100793","url":null,"abstract":"<div><div>Individuals with prenatal alcohol exposure (PAE) are at increased risk for experiencing early-life adversity (ELA), which may contribute to their heightened vulnerability to mental health problems. Using rat models, we examined the independent and interactive effects of PAE (liquid ethanol diet) and ELA (limited bedding) on emotional regulation, specifically anxiety- and depressive-like behaviors, and assessed neuroimmune alterations in the amygdala and hypothalamus during early and late adolescence as a potential underlying mechanism. Our results indicate that PAE induced anxiety-like behaviors across multiple tasks. PAE females exhibited anxiety-like behavior in the open field during both stages, whereas PAE males and females showed anxiety-like behavior in the light-dark test during early adolescence. In the forced swim test, depressive-like behavior was reduced in PAE females but increased in PAE males during late adolescence. ELA also produced sex- and age-dependent effects, increasing anxiety-like behavior in females during both stages and in males during early adolescence, and enhancing depressive-like behavior in both sexes during late adolescence. Importantly, ELA did not exacerbate PAE-related behavioral alterations. Neuroimmune analyses revealed age-, sex-, and region-specific cytokine changes: PAE induced a strong proinflammatory bias in the amygdala of females and altered both anti- and proinflammatory cytokines in the hypothalamus of males and females. In contrast, ELA effects were milder, with both the amygdala and hypothalamus similarly affected across sexes. Together, these findings indicate that PAE and ELA independently disrupt neuroimmune signaling and emotional regulation, supporting the hypothesis that cytokine dysregulation contributes to long-term vulnerability to emotional dysregulation.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100793"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147399883","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":"Resilience in motion: emerging perspectives on stress, substance use and youth","authors":"P. Sampedro-Piquero","doi":"10.1016/j.ynstr.2026.100783","DOIUrl":"10.1016/j.ynstr.2026.100783","url":null,"abstract":"<div><div>Adolescence and young adulthood are developmental stages characterized by heightened stress sensitivity and limited cognitive control. The identification of the risk factors of alcohol consumption in these stages is crucial for early interventions focused on reducing harmful alcohol use. This review examines how exercise can modulate stress responses, reduce cravings, and preserve cognitive and emotional functioning. In animal models, it has been well described that exercise is able to reduce craving and protect cognitive and affective domains. Translational studies in young people with risky alcohol use (RAU) revealed comparable benefits. Acute aerobic exercise improved executive functions, such as verbal fluency, whereas stretching induced distinct neural oscillatory changes related to emotion regulation. These findings underscore the heterogeneous yet complementary effects of different exercise modalities, suggesting that tailored interventions may optimize outcomes. Future work will incorporate interoceptive measures to clarify the mechanisms linking stress dysregulation and RAU vulnerability, with particular attention to gender-related differences. Collectively, the evidence suggests that aerobic exercise may constitute a promising, feasible, and transdiagnostic intervention that strengthens stress-response systems, reduces craving, and fosters resilience in young people at risk of alcohol misuse, with women showing interoceptive deficits emerging as a particularly vulnerable subgroup.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"41 ","pages":"Article 100783"},"PeriodicalIF":3.6,"publicationDate":"2026-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081238","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":"Neuroplacentology of stress: Novel frontiers linking maternal mental health to offspring neurodevelopment","authors":"Cristiana Cruceanu","doi":"10.1016/j.ynstr.2025.100778","DOIUrl":"10.1016/j.ynstr.2025.100778","url":null,"abstract":"<div><div>Neuroplacentology is an emerging interdisciplinary field integrating molecular neuroscience, placental biology, environmental modeling, and single-cell techniques to study stress-related neurodevelopmental programming. The placenta, once considered merely a conduit between mother and fetus, is now recognized as an important regulator of fetal brain development and a mediator of prenatal maternal stress and other exposures. To highlight this important aspect of the neurobiology of stress, this review outlines how maternal stress, genetic susceptibility, and environmental exposures converge at the placenta-brain axis to influence offspring psychiatric vulnerability.</div><div>Risk and resilience for psychiatric conditions are shaped by interactions between genetic predisposition and environmental exposures, including during the highly plastic prenatal period. Prenatal stress exposure can alter neuronal differentiation, transcription factor gene-regulatory networks, and excitation/inhibition neuronal balance. In parallel, maternal metabolic disorders, placental endocrine dysregulation, and psychotropic medication exposure modulate neuroactive pathways critical to brain development. The placenta responds to these exposures and synthesizes key stress molecules such as corticotropin-releasing hormone, serotonin and other neuromodulators, highlighting its neuroregulatory role.</div><div>To exemplify the promising future of neuroplacentology for our understanding of perinatal health and stress research, this review highlights innovative methodological approaches such as human-specific placental organoid systems and single-cell multi-omics. I propose that future research should focus on identifying placental biomarkers predictive of neurodevelopmental outcomes and refining <em>in-vitro</em> models for testing pharmacological interventions in a non-invasive manner. Elucidating the mechanisms at the placenta-brain interface, could lead to a better understanding of the developmental origins of mental illness and inform early intervention strategies.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"40 ","pages":"Article 100778"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145925267","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":"Ventral pallidum GABA neuron inhibition augments context-appropriate defensive responses to learned threat cues","authors":"Erica M. Ramirez ,&nbsp;Maricela X. Martinez ,&nbsp;Ryan K. Rokerya ,&nbsp;Vanessa Alizo Vera ,&nbsp;Christina M. Ruiz ,&nbsp;Mitchell R. Farrell ,&nbsp;Shreeya A. Walawalkar ,&nbsp;Hazael Ramirez-Ramirez ,&nbsp;Grace J. Kollman ,&nbsp;Stephen V. Mahler","doi":"10.1016/j.ynstr.2026.100781","DOIUrl":"10.1016/j.ynstr.2026.100781","url":null,"abstract":"<div><div>The ventral pallidum (VP) is embedded within the brain circuits controlling motivated behavior, which are heavily implicated in addiction and other psychiatric disorders. Prior work showed that VP GABAergic neurons (VP^GABA) promote reward approach and seeking, while the intermixed population of VP glutamate neurons instead promote avoidance and aversion. Some have thus suggested a functional dichotomy between these VP subpopulations in reward versus threat. We test this hypothesis by asking how inhibiting VP^GABA impacts active and passive defensive responses to learned threat cues in the absence of rewards. We taught GAD1:Cre rats with inhibitory VP^GABA DREADDs (or control rats) that a metal probe delivers shock, or that a 20sec auditory cue precedes footshocks. These stimuli thereafter elicit active defensive burying, or passive freezing responses, respectively. We found that VP^GABA inhibition with CNO markedly increased stimulus-appropriate defensive responses to both types of learned threats, but failed to consistently alter new learning about them—suggesting VP^GABA mediates aversive motivation but not memory formation. VP^GABA inhibition also altered threat-related c-Fos expression within VP cell populations, and in their efferent target lateral habenula, but not mediodorsal thalamus—pointing to potential underlying circuit mechanisms of defensive responses. Results indicate that VP^GABA neurons not only promote reward seeking as previously reported, but that they may also actively inhibit defensive responses to threats that might otherwise compete with reward seeking. This refines our understanding of subcortical valanced motivation circuits, and may suggest new targets for intervening in disorders like addiction and depression.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"40 ","pages":"Article 100781"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146022598","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}