Neurobiology of Stress最新文献

{"title":"Youth mental health crisis: A translational view of the COVID-19 pandemic","authors":"Thorhildur Halldorsdottir","doi":"10.1016/j.ynstr.2025.100738","DOIUrl":"10.1016/j.ynstr.2025.100738","url":null,"abstract":"<div><div>Mental health problems among children and adolescents have increased over the past two decades, a trend that was further exacerbated by the COVID-19 pandemic. To improve prevention and treatment strategies, developmentally informed and data-driven multidisciplinary approaches are urgently needed to clarify the mechanisms underlying youth vulnerability and resilience. Stress and trauma exposure are among the strongest predictors of youth mental health problems; however, most children and adolescents remain resilient despite such exposures. The widespread and heterogeneous challenges posed by the COVID-19 pandemic offer a unique opportunity to examine, at scale, who develops mental health problems under stress and who remains resilient. Integrating emerging findings on pandemic-related risk and protective factors with evidence from animal models can illuminate sensitive developmental periods of heightened susceptibility to environmental influence and biological embedding. This approach can identify when, how, and through what pathways mental health problems emerge, including gene–environment interactions and epigenetic mechanisms. Such knowledge will inform both behavioral and pharmacological interventions, pinpointing not only specific treatment targets but also the optimal timing for intervention to be the most effective.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100738"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313740","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":"Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides","authors":"Katrina Z. Edmond ,&nbsp;Natalie Matosin","doi":"10.1016/j.ynstr.2025.100739","DOIUrl":"10.1016/j.ynstr.2025.100739","url":null,"abstract":"<div><div>Steroid hormones and neurosteroids (collectively neuroactive steroids), alongside neuropeptides, are key modulators of the central nervous system. These signalling molecules integrate environmental cues into neurobiological responses by regulating gene and protein expression in a cell-type-specific manner. Specifically, neuroactive steroids and neuropeptides modulate the hypothalamic-pituitary-adrenal axis to influence excitatory/inhibitory balance in the brain and broadly impact mood, cognition, and memory. Despite their central role in brain function, these signalling systems remain historically understudied, exposing a major gap in our understanding of stress-related psychiatric disorders, and posing a valuable opportunity for therapeutic innovation. Foundational studies using histology, genetic manipulation, and bulk transcriptomic approaches, primarily in rodent models, have provided critical insights into their roles. However, these traditional methods lack the resolution to capture region- and cell-specific mechanisms, which are needed to develop precision medicine approaches. The emergence of single-cell and spatial technologies now offers unprecedented insight into the precise cellular, molecular and spatial context in which neuroactive steroid and neuropeptide signalling occurs. By moving beyond cell-type-averaged measures, these tools enable detailed mapping of transcriptional and proteomic changes across specific brain areas and cell-types, helping to identify the microenvironments in which these systems become dysregulated. This review synthesises current knowledge of neuroactive steroids and neuropeptides in stress biology and psychiatric illness and discusses how cutting-edge molecular profiling technologies are beginning to transform our ability to study, and therapeutically target, this complex and dynamic neuroendocrine network.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100739"},"PeriodicalIF":4.3,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144240277","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":"Mechanisms of childhood trauma: an integrative review of a multimodal, transdiagnostic pathway","authors":"J.M. Pasteuning ,&nbsp;C. Broeder ,&nbsp;T.A.A. Broeders ,&nbsp;R.G.G. Busby ,&nbsp;A.W. Gathier ,&nbsp;E. Kuzminskaite ,&nbsp;F. Linsen ,&nbsp;C.P. Souama ,&nbsp;J.E. Verhoeven ,&nbsp;M.S.C. Sep ,&nbsp;C.H. Vinkers","doi":"10.1016/j.ynstr.2025.100737","DOIUrl":"10.1016/j.ynstr.2025.100737","url":null,"abstract":"<div><div>Childhood trauma (CT), conceptualized as emotional, physical or sexual abuse or emotional or physical neglect before the age of 18, is a risk factor for the emergence and poorer course of many mental and somatic disorders. The mechanisms underlying the impact of CT range from (neuro)biological changes (e.g., epigenetics, hypothalamic–pituitary–adrenal axis, and brain structure/function) to psychosocial mechanisms (e.g., personality, attachment, emotion regulation, and coping), and behavioral factors (e.g., smoking and exercise). Given the interrelatedness of mechanisms, there is a need for research that integrates the effects of CT across modalities. We aim to integrate (neuro)biological, psychosocial and behavioral mechanisms of CT in health and across mental and somatic disorders. The multimodal impact of CT requires more recognition in research and clinical practice and should be considered independent of current health status and diagnostic categories. Additionally, research should incorporate the impact of (daily life) stress to provide a more comprehensive understanding of the impact of CT. These recommendations may improve understanding, treatment and eventually prevention of CT-related health problems.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100737"},"PeriodicalIF":4.3,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230688","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":"Probiotics restore impaired spatial cognition and synaptic plasticity of prenatally-stressed male rats: focus on hippocampal and intestinal tight junctions","authors":"Fatemeh Aghighi Bidgoli ,&nbsp;Sayyed Alireza Talaei ,&nbsp;Abolfazl Azami Tameh ,&nbsp;Mahmoud Salami","doi":"10.1016/j.ynstr.2025.100736","DOIUrl":"10.1016/j.ynstr.2025.100736","url":null,"abstract":"<div><div>Bidirectional communication between the gut microbiota and the nervous system founded the gut-microbiota-brain axis, substantially affects numerous vital functions of the body. Stress, as the body's natural reaction to stressful situations, in turn, affects the functioning of various organs. Through evaluating long-term potentiation (LTP) and spatial memory assessment using the Morris water maze, we aimed to examine the effect of prenatal stress on the electrophysiological and behavioral aspects of hippocampus-dependent spatial memory. The relationship of the synaptic plasticity and learning and memory with the hypothalamus-pituitary-adrenal (HPA) axis and the integrity of blood-brain and intestinal barriers were also examined. The experimental subjects were introduced to probiotic treatment to assess how the supplementation influences stress-related alterations. The prenatal stress effectively impaired both LTP occurrence and behavioral function. It also led to disruption of blood-brain and gut barriers and increased serum level of corticosterone. The probiotic supplementation positively affected the synaptic plasticity and learning and memory. It also improved the integrity of both barriers and reduced the stress hormone corticosterone. Whereas there is a reverse relationship between stress and the hippocampus-dependent spatial memory, normal stress hormone, and the integrity of intestinal and brain barriers, the probiotic supplements improve all impairments. We conclude that the HPA axis plus the blood-brain and intestinal barriers play a role in hippocampus-dependent spatial memory that are substantially affected by the beneficial gut and probiotic bacteria.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"37 ","pages":"Article 100736"},"PeriodicalIF":4.3,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144230689","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":"Regulation of behavioral responses to single prolonged stress in male and female rats: Role of PACAP","authors":"Marissa A. Smail ,&nbsp;Evelin M. Cotella ,&nbsp;Susan E. Martelle ,&nbsp;James B. Chambers ,&nbsp;Ria K. Parikh ,&nbsp;Christine E. Moore ,&nbsp;Ben A. Packard ,&nbsp;Nawshaba Nawreen ,&nbsp;Rachel D. Moloney ,&nbsp;James P. Herman","doi":"10.1016/j.ynstr.2025.100727","DOIUrl":"10.1016/j.ynstr.2025.100727","url":null,"abstract":"<div><div>Post-Traumatic Stress Disorder (PTSD) is a debilitating condition in which a traumatic experience triggers symptoms related to re-experiencing, avoidance, arousal, and mood dysregulation. PTSD negatively impacts 6 % of people during their lifetime, with women being disproportionally affected and exhibiting different, more severe symptoms than men. Despite this widespread impact, the molecular mechanisms underlying PTSD and its sex differences remain poorly understood. Pituitary Adenylate Cyclase-Activating Polypeptide (PACAP) is a neuropeptide which participates in fine-tuning circuitry throughout the brain and has been associated with PTSD in humans, especially in women. Here, we use Single Prolonged Stress (SPS), an animal model of PTSD, to explore the roles of PACAP and sex in PTSD-like behaviors. Specifically, a PACAP agonist or antagonist was infused into the infralimbic (IL) prefrontal cortex, a region key to regulating fear- and anxiety-related behaviors, prior to SPS in male and female rats. Rats were then tested in open field/novel object, elevated plus maze, and social interaction. Utilizing a behavioral indexing method, we were able to uncover SPS effects in PTSD-related behavioral domains that were differentially impacted by PACAP manipulations in males and females. While both sexes exhibited increased threat avoidance and decreased threat assessment following SPS, females increased sociability while males decreased sociability. Males also appeared to be protected by IL PACAP antagonism while female SPS phenotypes were exacerbated by IL PACAP agonism. Furthermore, RNAscope revealed that PACAP in the prefrontal cortex responds differently to SPS in males and females. Together, these findings suggest complex relationships between SPS, sex, and IL PACAP which may have important implications for treating PTSD in men and women.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100727"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143921567","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":"Dynamics of stress-induced c-fos expression in the rat prelimbic cortex: lessons from intronic and mature RNA and protein analyses","authors":"Patricia Molina ,&nbsp;Xavier Belda ,&nbsp;Sandra Beriain ,&nbsp;Sara Serrano ,&nbsp;Gentzane Compte ,&nbsp;Raül Andero ,&nbsp;Antonio Armario","doi":"10.1016/j.ynstr.2025.100729","DOIUrl":"10.1016/j.ynstr.2025.100729","url":null,"abstract":"<div><div>Despite the extensive use of <em>c-fos</em> as a marker of stress-induced neuronal activation, key aspects regarding its dynamics of expression remain poorly characterized. In the present study, we assessed in the prelimbic cortex of adult male rats the immediate transcriptional response of <em>c-fos</em> by measuring the heteronuclear (hn)RNA and mature (m)RNA expression by double fluorescent <em>in situ</em> hybridization as well as the c-Fos protein using immunofluorescence (FOS). We quantified in three different experiments the number of <em>c-fos</em> hnRNA+, mRNA+ and FOS+ neurons under basal conditions, immediately after different periods of immobilization stress (IMO), and after a recovery period. Our results indicate that stress induced a large increase in the number of positive neurons for all markers analyzed, each displaying a different time course. Moreover, our findings indicate that measuring the intensity of signal per neuron also provides relevant information. In addition, we report an increased number of FOS+ neurons after only 8–15 min of IMO, suggesting a surprisingly fast initiation of protein translation. Finally, the maturation from <em>c-fos</em> hnRNA+ to mRNA+ might depend on the duration and/or intensity of stress-induced activation. Our findings contribute to a better understanding of the dynamics of stress-induced <em>c-fos</em> expression and underscore the importance of examining multiple molecular components when using <em>c-fos</em> as a proxy of neuronal activation.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100729"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900049","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":"Corrigendum to ‘Fear conditioning and extinction distinctively alter bidirectional synaptic plasticity within the amygdala of an animal model of post-traumatic stress disorder’, Neurobiology of Stress, Vol 29C, 2024 Jan 12:29:100606","authors":"Kwanghoon Park,&nbsp;Hoyong Park,&nbsp;ChiHye Chung","doi":"10.1016/j.ynstr.2025.100731","DOIUrl":"10.1016/j.ynstr.2025.100731","url":null,"abstract":"","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100731"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184743","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":"Sex-dependent impact of parental verbal abuse on brain lateralization of language","authors":"Xingzhen Wang ,&nbsp;Jiaojian Wang ,&nbsp;Zhenglong Lin ,&nbsp;Yang Yang ,&nbsp;Min Xu","doi":"10.1016/j.ynstr.2025.100730","DOIUrl":"10.1016/j.ynstr.2025.100730","url":null,"abstract":"<div><h3>Background</h3><div>Child maltreatment profoundly impacts mental health and cognitive abilities, with effects varying according to the type of maltreatment. Parental verbal abuse (PVA) is a pervasive yet often overlooked form of child maltreatment linked to significant changes in brain structures crucial for language. This study investigated the impact of PVA on behavior, brain structure, and function related to language, examining how these effects may differ between females and males.</div></div><div><h3>Methods</h3><div>We recruited 142 adults who experienced varying levels of PVA during childhood. Participants completed questionnaires to assess their exposure to PVA, nonverbal abuse and neglect, and underwent cognitive tests to evaluate their language-related skills. We employed diffusion tensor imaging and functional magnetic resonance imaging to explore how PVA affect structural characteristics of the arcuate fasciculus (AF) and brain activation patterns during a sentence comprehension task.</div></div><div><h3>Results</h3><div>Hierarchical regressions revealed sex-dependent effects of PVA on the AF lateralization. In females, PVA exposure was associated with decreased leftward lateralization of the AF’s anterior segment and reduced frontal lateralization during sentence comprehension. Conversely, in males, PVA was related to increased leftward lateralization of the same segment, but this structural change did not correspond with significant effects on functional lateralization or language performance.</div></div><div><h3>Conclusions</h3><div>This study highlights the susceptibility of AF’s anterior segment and frontal activation to PVA, revealing distinct patterns between females and males. The findings underscore the necessity for future research to address these sex differences and develop targeted interventions to meet the distinct challenges that females and males may face.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100730"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143907874","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":"Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?","authors":"Alanna Kit ,&nbsp;Kate Conway ,&nbsp;Savannah Makarowski ,&nbsp;Grace O'Regan ,&nbsp;Josh Allen ,&nbsp;Sandy R. Shultz ,&nbsp;Tamara S. Bodnar ,&nbsp;Brian R. Christie","doi":"10.1016/j.ynstr.2025.100732","DOIUrl":"10.1016/j.ynstr.2025.100732","url":null,"abstract":"<div><div>There is growing interest in exploring the therapeutic potential and mechanisms of action of psilocybin on stress-related neuropsychiatric disorders, including depression, generalized anxiety disorder (GAD), post-traumatic stress disorder (PTSD), obsessive-compulsive disorder (OCD), addiction, and disordered eating. Despite promising progressions in preclinical and clinical research, the neurobiological and physiological mechanisms underlying the therapeutic effects of psilocybin remain complex, involving multiple systems with numerous homeostatic feedback signaling pathways throughout the body. This review paper explores how psilocybin mechanistically interacts with the gut microbiota, enteric nervous system, hypothalamic-pituitary axis, and how psilocybin influences the bidirectional communication between peripheral and neuronal systems. Shifting towards a more integrated paradigm to unravel the mechanisms through which psilocybin affects the bidirectional gut-brain axis holds the promise of significantly advancing our understanding of psilocybin-based therapies from preparation of treatment, administration, to proceeding long-term integration. Such an understanding can extend beyond the treatment of psychiatric disorders, further encompassing a broader spectrum of inflammatory-related disorders.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100732"},"PeriodicalIF":4.3,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144125196","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":"Aggression as a contributing factor to social defeat and stress vulnerability","authors":"Megan M. John ,&nbsp;Melissa A. Pratt ,&nbsp;Jazmine D.W. Yaeger ,&nbsp;Renée A. Brummels ,&nbsp;Leighton J. Ledesma ,&nbsp;Lauren S. Meyer ,&nbsp;RaeAnn L. Hartwig ,&nbsp;Gabriel L. Legner ,&nbsp;Nathan G. Gilbertson ,&nbsp;Patrick J. Ronan ,&nbsp;Cliff H. Summers","doi":"10.1016/j.ynstr.2025.100728","DOIUrl":"10.1016/j.ynstr.2025.100728","url":null,"abstract":"<div><div>The Stress Alternatives Model (SAM) is a social defeat/avoidance paradigm developed in our lab that reveals evolutionarily conserved escape responses in fish, hamsters, rats, and mice. During social interactions in a neutral arena, available escape routes sized exclusively for smaller test animals allow for avoidance of a social aggressor. This 4-day social interaction protocol pairs C57BL/6N test mice and a larger, novel, aggressive CD1 mouse each day. Although escape portals are available, and the CD1 aggressor is unremittingly antagonistic, only half of the mice tested utilize the escape tunnels, while escape latency dramatically decreases over time in mice that escape. We sought to determine whether aggression provided the trigger of two stress-related phenotypes that are produced by the SAM. The results suggest threat of aggression, determined by the first attack, is necessary for phenotype development, but the intensity of aggression over time does not determine which phenotype is chosen. Phenotypes are determined by responsiveness and counterbalanced neurocircuits that promote stress-resilience or vulnerability. These stress neurocircuits are modulated by orexins, through orexin 1 and 2 receptors (Orx₁, Orx₂), which promote pro-stress behaviors. In the primary pro-stress neurocircuitry of the aBLA, we examined Akt and mToR gene expression in stress-resilient (Escape) and -vulnerable (Stay) mice. The quantity of <em>Hcrtr</em>_<em>1</em> mRNA/cell was elevated in Stay mice, as were the mRNA/cell numbers for <em>Mtor</em>. However, the increase of <em>Akt</em>_<em>2</em> and <em>Mtor</em> mRNA/cell was not evident specifically in <em>Hcrtr</em>_<em>1</em> expressing cells, suggesting these molecular markers of neuroplasticity are not being activated by Orx₁ receptors.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100728"},"PeriodicalIF":4.3,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143881739","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}