Neurobiology of Stress最新文献

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Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides 扩大我们对精神疾病(不良)适应性应激生理学的理解:实现类固醇和神经肽的单细胞特征
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-06-06 DOI: 10.1016/j.ynstr.2025.100739
Katrina Z. Edmond , Natalie Matosin
{"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}
引用次数: 0
Mechanisms of childhood trauma: an integrative review of a multimodal, transdiagnostic pathway 儿童创伤的机制:多模式、跨诊断途径的综合回顾
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-06-03 DOI: 10.1016/j.ynstr.2025.100737
J.M. Pasteuning , C. Broeder , T.A.A. Broeders , R.G.G. Busby , A.W. Gathier , E. Kuzminskaite , F. Linsen , C.P. Souama , J.E. Verhoeven , M.S.C. Sep , C.H. Vinkers
{"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}
引用次数: 0
Probiotics restore impaired spatial cognition and synaptic plasticity of prenatally-stressed male rats: focus on hippocampal and intestinal tight junctions 益生菌恢复产前应激雄性大鼠空间认知和突触可塑性受损:关注海马和肠道紧密连接
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-06-01 DOI: 10.1016/j.ynstr.2025.100736
Fatemeh Aghighi Bidgoli , Sayyed Alireza Talaei , Abolfazl Azami Tameh , Mahmoud Salami
{"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}
引用次数: 0
Regulation of behavioral responses to single prolonged stress in male and female rats: Role of PACAP 单次长时间应激对雌雄大鼠行为反应的调节:PACAP的作用
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100727
Marissa A. Smail , Evelin M. Cotella , Susan E. Martelle , James B. Chambers , Ria K. Parikh , Christine E. Moore , Ben A. Packard , Nawshaba Nawreen , Rachel D. Moloney , James P. Herman
{"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}
引用次数: 0
Dynamics of stress-induced c-fos expression in the rat prelimbic cortex: lessons from intronic and mature RNA and protein analyses 应激诱导大鼠前边缘皮层c-fos表达的动态:内含子和成熟RNA和蛋白质分析的教训
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100729
Patricia Molina , Xavier Belda , Sandra Beriain , Sara Serrano , Gentzane Compte , Raül Andero , Antonio Armario
{"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}
引用次数: 0
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 “创伤后应激障碍动物模型中,恐惧条件反射和消退显著改变杏仁核内双向突触可塑性”,《应激神经生物学》,2024年1月12日:29 - 100606
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100731
Kwanghoon Park, Hoyong Park, ChiHye Chung
{"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}
引用次数: 0
Sex-dependent impact of parental verbal abuse on brain lateralization of language 父母言语虐待对语言脑侧化的性别依赖性影响
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100730
Xingzhen Wang , Jiaojian Wang , Zhenglong Lin , Yang Yang , Min Xu
{"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}
引用次数: 0
Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress? 肠脑轴能让我们深入了解裸盖菇素在减轻压力方面的治疗价值吗?
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100732
Alanna Kit , Kate Conway , Savannah Makarowski , Grace O'Regan , Josh Allen , Sandy R. Shultz , Tamara S. Bodnar , Brian R. Christie
{"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}
引用次数: 0
Aggression as a contributing factor to social defeat and stress vulnerability 攻击性是导致社会失败和压力脆弱性的一个因素
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-04-23 DOI: 10.1016/j.ynstr.2025.100728
Megan M. John , Melissa A. Pratt , Jazmine D.W. Yaeger , Renée A. Brummels , Leighton J. Ledesma , Lauren S. Meyer , RaeAnn L. Hartwig , Gabriel L. Legner , Nathan G. Gilbertson , Patrick J. Ronan , Cliff H. Summers
{"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 (Orx<sub>1</sub>, Orx<sub>2</sub>), 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><sub><em>1</em></sub> mRNA/cell was elevated in Stay mice, as were the mRNA/cell numbers for <em>Mtor</em>. However, the increase of <em>Akt</em><sub><em>2</em></sub> and <em>Mtor</em> mRNA/cell was not evident specifically in <em>Hcrtr</em><sub><em>1</em></sub> expressing cells, suggesting these molecular markers of neuroplasticity are not being activated by Orx<sub>1</sub> 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}
引用次数: 0
Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2 在雄性和雌性小鼠中,早期的逆境影响了CNTNAP2杂合的行为发育
IF 4.3 2区 医学
Neurobiology of Stress Pub Date : 2025-04-22 DOI: 10.1016/j.ynstr.2025.100726
Gabriele Chelini , Tommaso Fortunato-Asquini , Enrica Cerilli , Katia Monsorno , Benedetta Catena , Ginevra Matilde Dall’O’ , Rosa Chiara Paolicelli , Yuri Bozzi
{"title":"Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2","authors":"Gabriele Chelini ,&nbsp;Tommaso Fortunato-Asquini ,&nbsp;Enrica Cerilli ,&nbsp;Katia Monsorno ,&nbsp;Benedetta Catena ,&nbsp;Ginevra Matilde Dall’O’ ,&nbsp;Rosa Chiara Paolicelli ,&nbsp;Yuri Bozzi","doi":"10.1016/j.ynstr.2025.100726","DOIUrl":"10.1016/j.ynstr.2025.100726","url":null,"abstract":"<div><div>The etiological complexity of psychiatric disorders arises from the dynamic interplay between genetic and environmental vulnerabilities. Among the environmental components, early-life adversities are a major risk factor for developing a psychiatric condition. Yet, the interaction between adversities early in life and genetic vulnerability contributing to psychopathology is poorly understood. To fill this gap, we took advantage of the ideally controlled conditions of a pre-clinical approach. We raised a mouse model with genetic predisposition for multiple psychiatric disorders (autism spectrum, schizophrenia, bipolar disorder), the <em>Cntnap2</em><sup><em>+/−</em></sup> mouse, with limited bedding and nesting (LBN), a well-established paradigm to induce early-life stress in rodents. These mice were compared to LBN-raised <em>Cntnap2</em><sup><em>+/+</em></sup> littermates, as well as parallel groups of <em>Cntnap2</em><sup><em>+/+</em></sup> and <em>Cntnap2</em><sup><em>+/−</em></sup> raised in standard conditions. Using a battery for behavioral phenotyping we show that early-life adverse experience shapes non-overlapping phenotypic landscapes based on genetic predisposition. Specifically, LBN-raised <em>Cntnap2</em><sup><em>+/−</em></sup> mice displayed a perseverative risk-taking behavior in the elevated plus maze. Interestingly, this trait was highly predictive of their success in social interaction, suggesting that the intrusion of anxiety into the social behavioral domain may contribute to extreme gain- or loss-of function in sociability. Finally, we show that LBN promotes hypertrophy of post-synaptic densities in the basolateral nucleus of the amygdala (BLA), but only in <em>Cntnap2</em><sup><em>+/−</em></sup> raised in LBN this is associated with microglia abnormalities. We conclude that the interplay between early-life adversities and <em>Cntnap2</em> haploinsufficiency alters emotion regulation in mice, putatively as a consequence of deficient synaptic scaling in the BLA.</div></div>","PeriodicalId":19125,"journal":{"name":"Neurobiology of Stress","volume":"36 ","pages":"Article 100726"},"PeriodicalIF":4.3,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143876793","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}
引用次数: 0
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