Neurobiology of Stress最新文献_第6页

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 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-06-06 DOI: 10.1016/j.ynstr.2025.100739

Katrina Z. Edmond , Natalie Matosin

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.

类固醇激素和神经类固醇（统称为神经活性类固醇）与神经肽一起是中枢神经系统的关键调节剂。这些信号分子通过以细胞类型特异性的方式调节基因和蛋白质的表达，将环境信号整合到神经生物学反应中。具体来说，神经活性类固醇和神经肽调节下丘脑-垂体-肾上腺轴，从而影响大脑的兴奋/抑制平衡，并广泛影响情绪、认知和记忆。尽管这些信号系统在大脑功能中起着核心作用，但它们在历史上仍未得到充分研究，这暴露了我们对压力相关精神疾病的理解存在重大差距，并为治疗创新提供了宝贵的机会。利用组织学、遗传操作和大量转录组学方法（主要是在啮齿动物模型中）进行的基础研究，为它们的作用提供了重要的见解。然而，这些传统方法缺乏捕捉区域和细胞特异性机制的分辨率，而这正是开发精准医学方法所需要的。单细胞和空间技术的出现现在提供了前所未有的深入了解神经活性类固醇和神经肽信号发生的精确细胞，分子和空间背景。通过超越细胞类型平均测量，这些工具能够详细绘制特定大脑区域和细胞类型的转录和蛋白质组学变化，有助于识别这些系统失调的微环境。这篇综述综合了应激生物学和精神疾病中神经活性类固醇和神经肽的最新知识，并讨论了尖端的分子分析技术如何开始改变我们研究和治疗这个复杂和动态的神经内分泌网络的能力。

{"title":"Expanding our understanding of (mal)adapted stress physiology in psychiatric disorders: achieving single-cell characterisation of steroids and neuropeptides","authors":"Katrina Z. Edmond , 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 Q1 NEUROSCIENCES

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

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.

儿童创伤（CT）的概念是18岁之前的情感、身体或性虐待或情感或身体忽视，是许多精神和身体疾病出现和恶化的一个风险因素。CT影响的潜在机制包括从（神经）生物学变化（如表观遗传学、下丘脑-垂体-肾上腺轴和大脑结构/功能）到社会心理机制（如个性、依恋、情绪调节和应对）和行为因素（如吸烟和锻炼）。鉴于机制的相互关联性，有必要研究整合CT跨模式的影响。我们的目标是整合（神经）生物学，社会心理和行为机制的CT在健康和跨精神和躯体疾病。CT的多模式影响需要在研究和临床实践中得到更多的认可，并且应该独立于当前的健康状况和诊断类别。此外，研究应纳入（日常生活）压力的影响，以便更全面地了解CT的影响。这些建议可能会提高对ct相关健康问题的理解、治疗和最终预防。

{"title":"Mechanisms of childhood trauma: an integrative review of a multimodal, transdiagnostic pathway","authors":"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","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 Q1 NEUROSCIENCES

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

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.

肠道微生物群和神经系统之间的双向交流建立了肠道-微生物群-大脑轴，实质性地影响了身体的许多重要功能。压力，作为身体对压力情况的自然反应，反过来影响各种器官的功能。通过Morris水迷宫的长时程增强（LTP）和空间记忆评估，探讨产前应激对海马依赖空间记忆电生理和行为方面的影响。研究了突触可塑性和学习记忆与下丘脑-垂体-肾上腺（HPA）轴、血脑和肠屏障完整性的关系。实验对象被引入益生菌治疗，以评估补充如何影响与压力相关的变化。产前应激有效地损害了LTP的发生和行为功能。它还会破坏血脑和肠道屏障，增加血清皮质酮水平。补充益生菌对突触可塑性和学习记忆有积极影响。它还改善了屏障的完整性，降低了应激激素皮质酮。尽管压力与海马体依赖的空间记忆、正常应激激素以及肠道和脑屏障的完整性之间存在相反的关系，但益生菌补充剂可以改善所有损伤。我们的结论是，HPA轴加上血脑和肠道屏障在海马体依赖的空间记忆中发挥作用，这在很大程度上受到有益肠道和益生菌的影响。

{"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 , Sayyed Alireza Talaei , Abolfazl Azami Tameh , 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 Q1 NEUROSCIENCES

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

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.

创伤后应激障碍（PTSD）是一种使人衰弱的疾病，在这种疾病中，创伤经历会引发与重新体验、逃避、觉醒和情绪失调相关的症状。创伤后应激障碍对6%的人产生负面影响，女性受到的影响不成比例，表现出不同的、比男性更严重的症状。尽管有这种广泛的影响，但PTSD的分子机制及其性别差异仍然知之甚少。垂体腺苷酸环化酶激活多肽（PACAP）是一种参与整个大脑微调回路的神经肽，与人类，特别是女性的创伤后应激障碍有关。本研究利用创伤后应激障碍（PTSD）动物模型单一延长应激（SPS），探讨PACAP和性别在PTSD样行为中的作用。具体来说，在雄性和雌性大鼠SPS之前，将PACAP激动剂或拮抗剂注入边缘下（IL）前额皮质，这是调节恐惧和焦虑相关行为的关键区域。然后对大鼠进行开阔场地/新奇物体、高架+迷宫和社会互动测试。利用行为索引方法，我们能够发现男性和女性在创伤后应激相关行为领域中受到PACAP操作差异影响的SPS效应。在SPS之后，两性都表现出了更高的威胁规避能力和更低的威胁评估能力，但女性的社交能力增强了，而男性的社交能力减弱了。IL - PACAP拮抗剂对雄性也有保护作用，而IL - PACAP拮抗剂则加剧了雌性SPS表型。此外，RNAscope显示，男性和女性前额叶皮层的PACAP对SPS的反应不同。总之，这些发现提示了SPS、性别和IL - PACAP之间的复杂关系，这可能对治疗男性和女性创伤后应激障碍具有重要意义。

{"title":"Regulation of behavioral responses to single prolonged stress in male and female rats: Role of PACAP","authors":"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","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 Q1 NEUROSCIENCES

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

Despite the extensive use of c-fos 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 c-fos by measuring the heteronuclear (hn)RNA and mature (m)RNA expression by double fluorescent in situ hybridization as well as the c-Fos protein using immunofluorescence (FOS). We quantified in three different experiments the number of c-fos 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 c-fos 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 c-fos expression and underscore the importance of examining multiple molecular components when using c-fos as a proxy of neuronal activation.

尽管c-fos被广泛用作应激诱导神经元激活的标记物，但其表达动力学的关键方面仍然缺乏表征。在本研究中，我们通过双荧光原位杂交检测异核（hn）RNA和成熟(m)RNA的表达，以及免疫荧光（FOS）检测c-fos蛋白的表达，评估了成年雄性大鼠前边缘皮层c-fos的即时转录反应。在三个不同的实验中，我们量化了基础条件下、不同时期固定应激（IMO）后和恢复期后c-fos hnRNA+、mRNA+和FOS+神经元的数量。我们的研究结果表明，应激诱导所有标记的阳性神经元数量大量增加，每个标记显示不同的时间过程。此外，我们的研究结果表明，测量每个神经元的信号强度也提供了相关信息。此外，我们报告了IMO仅8-15分钟后FOS+神经元数量的增加，这表明蛋白质翻译的启动速度惊人。最后，从c-fos hnRNA+到mRNA+的成熟可能取决于应激诱导激活的持续时间和/或强度。我们的研究结果有助于更好地理解应激诱导的c-fos表达的动力学，并强调了在使用c-fos作为神经元激活的代理时检查多种分子成分的重要性。

{"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 , Xavier Belda , Sandra Beriain , Sara Serrano , Gentzane Compte , Raül Andero , 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 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-05-01 DOI: 10.1016/j.ynstr.2025.100731

Kwanghoon Park, Hoyong Park, ChiHye Chung

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 Q1 NEUROSCIENCES

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

Background

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.

Methods

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.

Results

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.

Conclusions

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.

儿童虐待严重影响心理健康和认知能力，其影响因虐待类型而异。父母言语虐待（PVA）是一种普遍存在但却经常被忽视的儿童虐待形式，与对语言至关重要的大脑结构的显著变化有关。这项研究调查了PVA对行为、大脑结构和语言相关功能的影响，并研究了这些影响在女性和男性之间的差异。方法：我们招募了142名在童年时期经历过不同程度PVA的成年人。参与者完成了问卷调查，以评估他们对PVA、非语言虐待和忽视的暴露程度，并进行了认知测试，以评估他们的语言相关技能。采用弥散张量成像和功能磁共振成像技术，探讨PVA对句子理解任务中弓形束结构特征和脑激活模式的影响。结果分层回归显示PVA对房颤侧化的影响具有性别依赖性。在女性中，PVA暴露与房颤前段左偏侧化减少和句子理解过程中额侧化减少有关。相反，在男性中，PVA与同一节段向左偏侧化增加有关，但这种结构变化对功能偏侧化或语言表现没有显著影响。结论本研究强调了房颤前段和额叶活化对PVA的易感性，并在女性和男性之间显示出不同的模式。这些发现强调了未来研究解决这些性别差异的必要性，并制定有针对性的干预措施，以应对女性和男性可能面临的不同挑战。

{"title":"Sex-dependent impact of parental verbal abuse on brain lateralization of language","authors":"Xingzhen Wang , Jiaojian Wang , Zhenglong Lin , Yang Yang , 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 Q1 NEUROSCIENCES

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

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.

人们对探索裸盖菇素治疗压力相关神经精神疾病的潜力和作用机制越来越感兴趣，包括抑郁症、广泛性焦虑症（GAD）、创伤后应激障碍（PTSD）、强迫症（OCD）、成瘾和饮食失调。尽管在临床前和临床研究中取得了有希望的进展，裸盖菇素治疗效果的神经生物学和生理机制仍然很复杂，涉及多个系统，体内有许多稳态反馈信号通路。本文综述了裸盖菇素与肠道微生物群、肠道神经系统、下丘脑-垂体轴的相互作用机制，以及裸盖菇素如何影响外周系统和神经系统之间的双向通讯。转向一个更综合的范式来揭示裸盖菇素影响双向肠-脑轴的机制，有望显著推进我们对基于裸盖菇素的疗法的理解，从治疗的准备、给药到进行长期整合。这样的理解可以扩展到精神疾病的治疗之外，进一步涵盖更广泛的炎症相关疾病。

{"title":"Can the gut-brain axis provide insight into psilocybin's therapeutic value in reducing stress?","authors":"Alanna Kit , Kate Conway , Savannah Makarowski , Grace O'Regan , Josh Allen , Sandy R. Shultz , Tamara S. Bodnar , 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 Q1 NEUROSCIENCES

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

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 Hcrtr₁ mRNA/cell was elevated in Stay mice, as were the mRNA/cell numbers for Mtor. However, the increase of Akt₂ and Mtor mRNA/cell was not evident specifically in Hcrtr₁ expressing cells, suggesting these molecular markers of neuroplasticity are not being activated by Orx₁ receptors.

压力替代模型（SAM）是我们实验室开发的一种社会失败/回避范式，揭示了鱼、仓鼠、大鼠和小鼠在进化上保守的逃避反应。在中性竞技场的社会互动中，小型实验动物专用的逃生路线可以避免社会攻击者。这项为期4天的社会互动方案每天将C57BL/6N测试小鼠和一只更大的、新颖的、具有攻击性的CD1小鼠配对。虽然逃逸通道是可用的，并且CD1侵略者是持续拮抗的，但只有一半的小鼠利用了逃逸通道，而逃逸的小鼠的逃逸潜伏期随着时间的推移显着减少。我们试图确定攻击性是否触发了由SAM产生的两种与压力相关的表型。结果表明，由第一次攻击决定的攻击威胁对于表型的发展是必要的，但随着时间的推移，攻击的强度并不能决定选择哪种表型。表型是由反应性和促进应激恢复或脆弱性的平衡神经回路决定的。这些应激神经回路由食欲素调节，通过食欲素1和2受体（Orx1, Orx2），促进促应激行为。在aBLA的主要前应激神经回路中，我们检测了应激复原（Escape）和应激脆弱（Stay）小鼠中Akt和mToR基因的表达。Stay小鼠的Hcrtr1 mRNA/细胞数量升高，Mtor的mRNA/细胞数量也升高。然而，在表达Hcrtr1的细胞中，Akt2和Mtor mRNA/cell的增加并不明显，这表明这些神经可塑性的分子标记并未被Orx1受体激活。

{"title":"Aggression as a contributing factor to social defeat and stress vulnerability","authors":"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","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 Q1 NEUROSCIENCES

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

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 Cntnap2^+/− 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 Cntnap2^+/+ littermates, as well as parallel groups of Cntnap2^+/+ and Cntnap2^+/− 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 Cntnap2^+/− 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 Cntnap2^+/− raised in LBN this is associated with microglia abnormalities. We conclude that the interplay between early-life adversities and Cntnap2 haploinsufficiency alters emotion regulation in mice, putatively as a consequence of deficient synaptic scaling in the BLA.

精神疾病的病因复杂性源于遗传和环境脆弱性之间的动态相互作用。在环境因素中，早期生活的逆境是发展成精神疾病的主要危险因素。然而，生命早期的逆境与遗传易感性之间的相互作用对精神病理的影响却知之甚少。为了填补这一空白，我们利用了临床前方法的理想控制条件。我们建立了一个具有多种精神疾病遗传易感性（自闭症谱系、精神分裂症、双相情感障碍）的小鼠模型，Cntnap2+/−小鼠，具有有限的床上和筑巢（LBN），这是一种在啮齿动物中诱导早期生活压力的成熟范例。将这些小鼠与lbn饲养的Cntnap2+/+幼鼠，以及在标准条件下饲养的Cntnap2+/+和Cntnap2+/−平行组进行比较。使用行为表型电池，我们表明，早期生活中的不良经历塑造了基于遗传易感性的非重叠表型景观。具体来说，lbn饲养的Cntnap2+/−小鼠在升高+迷宫中表现出持久性的冒险行为。有趣的是，这一特征高度预测了他们在社会交往中的成功，这表明焦虑对社会行为领域的入侵可能会导致社交功能的极端增益或丧失。最后，我们发现LBN促进杏仁核基底外侧核（BLA）突触后密度的肥大，但仅在LBN中Cntnap2+/−升高的情况下，这与小胶质细胞异常有关。我们得出结论，幼年逆境和cnnap2单倍不足之间的相互作用改变了小鼠的情绪调节，推测这是由于BLA突触缩放缺陷造成的。

{"title":"Early-life adversities compromise behavioral development in male and female mice heterozygous for CNTNAP2","authors":"Gabriele Chelini , Tommaso Fortunato-Asquini , Enrica Cerilli , Katia Monsorno , Benedetta Catena , Ginevra Matilde Dall’O’ , Rosa Chiara Paolicelli , 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