Neurobiology of Stress最新文献_第5页

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。

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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。

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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。

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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。

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引用次数: 0

Building a social brain: Cells, circuits and behavior across the lifespan 构建社会性大脑：生命周期中的细胞、回路和行为

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-04-08 DOI: 10.1016/j.ynstr.2025.100725

Maya Opendak

Disrupted social behavior is a fundamental indicator of compromised mental health, such as anxiety and depression, and serves as an early diagnostic marker for disorders that can develop later in life. However, our understanding of how the neural circuits for social behavior develop and how environmental disturbances at various developmental stages affect infant behavior is limited. Through my research with rats, I have established a foundation for identifying specific neuroanatomical circuits in infants that produce age-appropriate social behavior and how these systems may change in response to adversity. Overall, these studies have helped generate technical and conceptual advances in our understanding of social development and early life stress. These studies have employed multiple levels of analysis and functional brain dissection to identify novel targets of early social stress and measure how the infant brain responds to social information in typical and perturbed development.

社交行为紊乱是焦虑和抑郁等心理健康受损的基本指标，也是可能在以后生活中出现的疾病的早期诊断标志。然而，我们对社会行为的神经回路如何发展以及不同发育阶段的环境干扰如何影响婴儿行为的理解是有限的。通过我对老鼠的研究，我已经建立了一个基础，可以识别婴儿体内产生与年龄相适应的社会行为的特定神经解剖学回路，以及这些系统如何在逆境中发生变化。总的来说，这些研究帮助我们在理解社会发展和早期生活压力方面取得了技术和概念上的进步。这些研究采用多层次的分析和功能性脑解剖来确定早期社会压力的新目标，并测量婴儿大脑如何在典型和紊乱的发展中对社会信息作出反应。

引用次数: 0

An inverted U-shaped relationship between chronic stress and the motivation to expend effort for reward 长期压力与为回报而付出努力的动机之间呈倒u型关系

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-04-05 DOI: 10.1016/j.ynstr.2025.100724

Wei Yi , Xin Li , Wangxiao Chen , Linlin Yan , Fei Xin , Tony W. Buchanan , Jianhui Wu

Dysfunction in the motivation to expend effort for reward is considered a crucial symptom of stress-related mental illness. Few studies have explored the relationship between chronic stress and the motivation to exert effort for reward, along with its underlying neural mechanisms. We investigated this relationship in ninety undergraduates who were undergoing a chronic stressor: preparing for the National Postgraduate Entrance Examination (NPEE). Students engaged in an effort-reward task while EEG signals were recorded, wherein they could accept or reject an offer to expend effort for another opportunity to obtain the reward. Participants’ chronic stress levels were assessed using the Perceived Stress Scale (PSS) and their decision was further captured by a drift-diffusion model (DDM). Compared to reward omission, reward delivery led to increased amplitude of the reward positivity (RewP) ERP waveform, particularly in extra reward trials relative to regular trials. Importantly, the PSS score showed an inverted U-shaped relationship with the motivation indicators, including offer acceptance rate (behavioral index), drift rate (model parameter), and ΔRewP (i.e., the difference in RewP in response to reward delivery compared to reward omission, ERP component). These findings suggest an inverted U-shaped relationship between chronic stress and motivation, suggesting that individuals display diminished motivation when exposed to low or high levels, relative to moderate levels, of chronic stress. Our study holds significant implications for understanding both vulnerability and resilience to stress-related mental disorders.

为获得奖励而付出努力的动机障碍被认为是与压力有关的精神疾病的一个重要症状。很少有研究探索慢性压力与努力获得奖励的动机之间的关系，以及其潜在的神经机制。本研究以90名正经历慢性压力源的大学生为研究对象，调查了这一关系。在记录脑电图信号的同时，学生们参与了一项努力-奖励任务，其中他们可以接受或拒绝为另一个获得奖励的机会而付出努力的提议。采用感知压力量表（PSS）评估参与者的慢性压力水平，并通过漂移-扩散模型（DDM）进一步捕捉他们的决策。与不给予奖励相比，给予奖励导致奖励积极性（RewP） ERP波形的振幅增加，特别是在额外奖励试验中。重要的是，PSS得分与动机指标呈倒u型关系，包括提供接受率（行为指标）、漂移率（模型参数）和ΔRewP（即奖励交付与奖励遗漏的RewP差异，ERP成分）。这些发现表明，慢性压力和动机之间呈倒u型关系，表明个体在暴露于低水平或高水平（相对于中等水平）的慢性压力时，其动机会减弱。我们的研究对理解与压力相关的精神障碍的脆弱性和恢复力具有重要意义。

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引用次数: 0

The insular cortex-nucleus tractus solitarius glutamatergic pathway involved in acute stress-induced gastric mucosal damage in rats 大鼠脑岛皮层-孤束核谷氨酸能通路参与急性应激性胃粘膜损伤

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-04-01 DOI: 10.1016/j.ynstr.2025.100723

Zepeng Wang , Xinyu Li , Yuanyuan Li , Xuehan Sun , Yuxue Wang , Tong Lu , Dongqin Zhao , Xiaoli Ma , Haiji Sun

Previous studies have shown that acute stress-induced gastric mucosal damage is linked to excessive activation of parasympathetic nervous system. The Insular Cortex (IC), the higher centers of the parasympathetic nervous system, serves as both the integration site of gastric sensory information and play a crucial role in the regulation of gastric function. However, whether the IC is involved in Restraint water-immersion stress (RWIS)-induced gastric mucosal damage has not been reported. In this study, we examined the expression of neuronal c-Fos, PSD95 and SYN-1 protein expression in IC during RWIS by immunofluorescence and western blot techniques, as well as assessed IC blood oxygenation level dependant (BOLD) through functional MRI. Chemical genetics techniques specifically modulate the activity of IC glutamatergic neurons and IC-nucleus tractus solitary (NTS) glutamatergic pathway to elucidate their contributions to RWIS-induced gastric mucosal damage. The results showed that the expression of c-Fos, PSD95, and SYN-1 protein in IC increased significantly after RWIS, along with a noticeable enhancement in fMRI signal intensity. Furthermore, inhibiting IC glutamatergic neurons and the IC-NTS glutamatergic neural pathway resulted in a significant reduction in gastric mucosal damage, an increase in the expression of Occludin, Claudin-1, and PCNA in the gastric wall, while the expression of nNOS decreased and CHAT increased. These findings suggest that during RWIS, IC glutaminergic neurons are activated, promoting stress-induced gastric mucosal damage through the IC-NTS-vagal nerve pathway.

以往的研究表明，急性应激性胃黏膜损伤与副交感神经系统过度激活有关。岛叶皮层（Insular Cortex， IC）是副交感神经系统的高级中枢，既是胃感觉信息的整合部位，又在胃功能的调节中起着至关重要的作用。然而，IC是否参与克制水浸应激（RWIS）诱导的胃粘膜损伤尚未见报道。在本研究中，我们通过免疫荧光和western blot技术检测了RWIS期间IC中神经元c-Fos、PSD95和SYN-1蛋白的表达，并通过功能MRI评估了IC血氧水平依赖性（BOLD）。化学遗传学技术特异性调节IC谷氨酸能神经元和IC核孤立束（NTS）谷氨酸能通路的活性，以阐明它们在rwi诱导的胃粘膜损伤中的作用。结果显示，RWIS后IC中c-Fos、PSD95、SYN-1蛋白的表达显著升高，fMRI信号强度明显增强。此外，抑制IC谷氨酸能神经元和IC- nts谷氨酸能神经通路导致胃粘膜损伤明显减轻，胃壁Occludin、Claudin-1和PCNA表达增加，nNOS表达减少，CHAT表达增加。这些结果表明，在RWIS期间，IC谷氨酰胺能神经元被激活，通过IC- nts -迷走神经通路促进应激诱导的胃粘膜损伤。

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引用次数: 0

Dynamic changes of serotonin transporter expression in the prefrontal cortex evoked by aggressive social interactions 攻击性社会互动诱发前额叶皮层血清素转运体表达的动态变化

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-03-26 DOI: 10.1016/j.ynstr.2025.100722

Huba Szebik , Christina Miskolczi , Bíborka Bruzsik , Gyula Balla , Soma Szabó , László Biró , Éva Mikics

Aggression is a complex behavior influenced by developmental experiences, internal state, and social context, yet its neurobiological underpinnings remain insufficiently understood. The serotonergic system, particularly the serotonin transporter (SERT), plays a crucial role in aggression regulation. Here, we investigated region-specific, dynamic changes in SERT expression following aggressive interactions and in mice subjected to early-life social adversity. We found that aggressive encounters (resident-intruder test) triggered a significant, rapid increase in SERT immunoreactivity within 90 min, accompanied by neuronal activation in aggression-related brain regions, including the medial prefrontal cortex (mPFC), lateral septum (LS), medial amygdala (MeA), ventromedial hypothalamus (VMHvl), lateral habenula (LH), and dorsal raphe (DR), but not in the paraventricular thalamus (PVT). Notably, this SERT upregulation occurred across the aggression circuitry but was accompanied by a significant increase in 5-HT levels only in the mPFC, a key region in top-down regulation of social and aggressive behavior. This SERT upregulation was not observed following exposure to a non-social challenge, suggesting that it may be more specifically associated with social contexts. Using super-resolution microscopy, we identified an increased density of SERT localization points within serotonergic mPFC axons after an aggressive encounter. Social isolation during adolescence, a model of early social neglect, impaired this rapid SERT response, particularly in the ventral and medial orbitofrontal regions, and altered the relationship between SERT levels and aggression-related behaviors. These findings demonstrate that SERT expression undergoes rapid, experience-dependent plasticity in response to social aggression, and that early-life adversity disrupts this adaptive mechanism, providing new insights into the serotonergic regulation of aggression and its potential relevance for stress-related social dysfunctions.

攻击是一种复杂的行为，受发育经历、内部状态和社会环境的影响，但其神经生物学基础仍未得到充分的了解。血清素能系统，特别是血清素转运体（SERT），在攻击调节中起着至关重要的作用。在这里，我们研究了SERT表达在攻击性相互作用后以及在幼年遭受社会逆境的小鼠中的区域特异性动态变化。我们发现，攻击性遭遇（驻地-入侵者测试）在90分钟内触发SERT免疫反应性显著、快速增加，并伴有与攻击相关的大脑区域的神经元激活，包括内侧前额叶皮层（mPFC）、外侧隔（LS）、内侧杏仁核（MeA）、下丘脑腹内侧（VMHvl）、外侧缰核（LH）和中叶背（DR），但室旁丘脑（PVT）没有神经元激活。值得注意的是，这种SERT上调发生在整个攻击回路中，但仅在mPFC（自上而下调节社交和攻击行为的关键区域）中伴随着5-HT水平的显著增加。这种SERT上调在暴露于非社会挑战后未被观察到，这表明它可能与社会环境更具体地相关。使用超分辨率显微镜，我们发现在侵袭性遭遇后，SERT定位点密度增加。青少年时期的社会孤立是早期社会忽视的一种模式，它损害了这种快速的SERT反应，特别是在腹侧和内侧眶额区，并改变了SERT水平与攻击相关行为之间的关系。这些发现表明，SERT的表达经历了快速的、经验依赖的可塑性，以应对社会攻击，而早期生活中的逆境破坏了这种适应机制，为5 -羟色胺对攻击的调节及其与压力相关的社会功能障碍的潜在相关性提供了新的见解。

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引用次数: 0

Sex-specific regulation of microglial MyD88 in HMGB1-Induced anxiety phenotype in mice hmgb1诱导小鼠焦虑表型中小胶质细胞MyD88的性别特异性调控

IF 4.3 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-03-23 DOI: 10.1016/j.ynstr.2025.100721

Ashleigh Rawls , Julia Dziabis , Dang Nguyen , Dilara Anbarci , Madeline Clark , Grace Zhang , Kafui Dzirasa , Staci D. Bilbo

Stress is a significant risk factor for the development and recurrence of anxiety disorders. Stress can profoundly impact the immune system, and lead to microglial functional alterations in the medial prefrontal cortex (mPFC), a brain region involved in the pathogenesis of anxiety. High mobility group box 1 protein (HMGB1) is a potent pro-inflammatory stimulus and danger-associated molecular pattern (DAMP) released from neuronal and non-neuronal cells following stress. HMGB1 provokes pro-inflammatory responses in the brain and, when administered locally, alters behavior in the absence of other stressors. In this study, we administered dsHMGB1 into the mPFC of male and female mice for 5 days to investigate the cellular and molecular mechanisms underlying HMGB1-induced behavioral dysfunction, with a focus on cell-type specificity and potential sex differences. Here, we demonstrate that dsHMGB1 infusion into the mPFC elicited behavior changes in both sexes but only altered microglial morphology robustly in female mice. Moreover, preventing microglial changes with cell-specific ablation of the MyD88 pathway prevented anxiety-like behaviors only in females. These results support the hypothesis that microglial MyD88 signaling is a critical mediator of HMGB1-induced stress responses, particularly in adult female mice.

压力是焦虑障碍发生和复发的重要危险因素。压力可以深刻地影响免疫系统，并导致内侧前额叶皮层（mPFC）的小胶质细胞功能改变，mPFC是一个参与焦虑发病机制的大脑区域。高迁移率组框1蛋白（HMGB1）是神经细胞和非神经细胞在应激后释放的一种有效的促炎刺激和危险相关分子模式（DAMP）。HMGB1在大脑中引起促炎反应，当局部使用时，在没有其他压力源的情况下改变行为。在这项研究中，我们将dsHMGB1注入雄性和雌性小鼠的mPFC 5天，研究hmgb1诱导行为功能障碍的细胞和分子机制，重点研究细胞类型特异性和潜在的性别差异。在这里，我们证明dsHMGB1输注到mPFC引起了两性的行为改变，但只在雌性小鼠中强烈地改变了小胶质细胞的形态。此外，通过细胞特异性消融MyD88通路来预防小胶质细胞的变化，仅在女性中阻止了焦虑样行为。这些结果支持了小胶质细胞MyD88信号是hmgb1诱导的应激反应的关键介质的假设，特别是在成年雌性小鼠中。

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引用次数: 0