Neurobiology of Stress最新文献_第3页

Exposure to early-life stress uncovers shared biological signatures underlying vulnerability in the habenula and insular cortex of male and female adult rats 暴露于早期生活压力揭示了雄性和雌性成年大鼠habenula和岛叶皮层中潜在脆弱性的共同生物学特征

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-16 DOI: 10.1016/j.ynstr.2025.100761

Valentina Zonca , Moira Marizzoni , Samantha Saleri , Monica Mazzelli , Giulia Petrillo , Maria Grazia Di Benedetto , Floriana De Cillis , Marco Andrea Riva , Annamaria Cattaneo

Early-life stress (ELS) is a well-known risk factor for the development of several mental disorders later in life. The effect of ELS can be twofold: resilient individuals adapt by perceiving stress as minimal, while vulnerable ones struggle to cope with it and are predisposed to the onset of psychopathology. Although it is known that different brain regions play a role in determining ELS resilience or vulnerability, the specific mechanisms remain unclear. This preclinical study examines the effects of prenatal stress (PNS) on the functional connectivity of habenula (Hb) and insular cortex (IC) and whether these alterations predispose to stress vulnerability in adulthood. PNS was associated with reduced social interaction in both male and female animals, suggesting the onset of a potentially altered behavioural phenotype. Transcriptomic analysis of vulnerable and resilient animals revealed profound PNS-induced gene expression changes in both Hb and IC, with sex-specific patterns. In vulnerable males, pathway analysis identified a shared molecular signature between Hb and IC primarily involving the activation of inflammation and collagen-related processes. In females, vulnerability was linked to downregulation of serotonin signaling, indicating an alternative pathway to stress susceptibility compared with males. Co-expression network analysis confirmed these findings, highlighting sex-dependent biological mechanisms underlying vulnerability. These results suggest that vulnerability to stress may emerge from functional interactions between Hb and IC, mediated by distinct and sex-specific pathways.

早期生活压力（ELS）是一种众所周知的风险因素，可导致生命后期出现多种精神障碍。ELS的影响可能是双重的：有弹性的个体通过将压力视为最小而适应，而脆弱的个体则努力应对压力，并倾向于精神病理的发作。虽然已知不同的大脑区域在决定ELS的恢复力或脆弱性方面发挥作用，但具体机制尚不清楚。本临床前研究探讨了产前应激（PNS）对habenula （Hb）和岛叶皮质（IC）功能连通性的影响，以及这些改变是否易导致成年后的应激易感性。在雄性和雌性动物中，PNS与社会互动减少有关，这表明一种潜在的改变行为表型的开始。易感动物和复原动物的转录组学分析显示，pns诱导的Hb和IC基因表达都发生了深刻的变化，并具有性别特异性。在易感男性中，通路分析确定了Hb和IC之间共享的分子特征，主要涉及炎症和胶原相关过程的激活。在女性中，脆弱性与血清素信号的下调有关，与男性相比，这表明了应激易感性的另一种途径。共表达网络分析证实了这些发现，强调了脆弱性背后的性别依赖生物学机制。这些结果表明，对应激的脆弱性可能来自Hb和IC之间的功能相互作用，由不同的性别特异性途径介导。

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引用次数: 0

High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression of Cldn5 高强度间歇训练通过缓解同型半胱氨酸诱导的Cldn5转录抑制改善慢性应激小鼠的认知功能障碍

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-15 DOI: 10.1016/j.ynstr.2025.100758

Zhao-Xin Sun , Mao-Yang Zhou , Jin-Shan Li , Yun Zhao , Fang Xie , Xue Wang , Hong Feng , Zhao-Wei Sun , Ling-Jia Qian

Chronic stress-induced blood-brain barrier (BBB) dysfunction contributes to neurological disorders, with homocysteine (HCY) as a key risk factor. Considering pharmacotherapy limitations, non-invasive interventions like high-intensity interval training (HIIT) are promising. To determine whether HIIT improves stress-induced BBB dysfunction and cognitive impairment, we first established a chronic unpredictable mild stress (CUMS) model and assigned mice into four groups: Control (Ctrl), CUMS, HIIT, and HIIT + CUMS. Here, we found that HIIT significantly ameliorated cognitive impairment in male CUMS mice, as evidenced by reduced escape latency in morris water maze and increased memory performance in novel object recognition test. HIIT also preserved BBB integrity by ameliorating the tight junction disruption and BBB hyper-permeability in stressed mice. Subsequently, to clarify the role of HCY in the HIIT-mediated effects, we established an HHCY model and divided mice into four groups: Ctrl, HIIT, HHCY, and HIIT + HHCY. The results showed that HIIT normalized the plasma and hippocampal HCY levels by restoring the expression of related metabolic enzymes including CBS, MTHFR and MS, and alleviated HHCY-induced cognitive decline and BBB damage. Further, HIIT reversed HCY-induced Claudin-5 downregulation by inhibiting H3K27me3 enrichment at the Cldn5 (the encoding gene of Claudin-5) promoter region. In addition, HIIT restored the expression of ETS1, one of the transcriptional activators of Cldn5, to facilitate the transcription of Cldn5 gene and the stabilization of BBB. Collectively, these findings reveal that HIIT improves chronic stress-induced cognitive impairment via eliminating the disruptive effects of HHCY on the BBB integrity, offering a non-pharmacological intervention potential for stress-related cognitive deficits.

慢性应激性血脑屏障（BBB）功能障碍有助于神经系统疾病，同型半胱氨酸（HCY）是一个关键的危险因素。考虑到药物治疗的局限性，像高强度间歇训练（HIIT）这样的非侵入性干预是有希望的。为了确定HIIT是否能改善应激诱导的血脑屏障功能障碍和认知障碍，我们首先建立了慢性不可预测轻度应激（CUMS）模型，并将小鼠分为四组：Control （Ctrl）、CUMS、HIIT和HIIT + CUMS。在此，我们发现HIIT显著改善了雄性CUMS小鼠的认知功能障碍，这可以通过减少morris水迷宫的逃避潜伏期和提高新物体识别测试的记忆表现来证明。HIIT还通过改善应激小鼠的紧密连接破坏和血脑屏障的超通透性来保持血脑屏障的完整性。随后，为了明确HCY在HIIT介导效应中的作用，我们建立了HHCY模型，并将小鼠分为Ctrl、HIIT、HHCY和HIIT + HHCY四组。结果表明，HIIT通过恢复CBS、MTHFR和MS等相关代谢酶的表达，使血浆和海马HCY水平正常化，减轻了hhcy引起的认知能力下降和血脑屏障损伤。此外，HIIT通过抑制Cldn5 （Cldn5的编码基因）启动子区域的H3K27me3富集，逆转了hcy诱导的Claudin-5下调。此外，HIIT恢复了Cldn5的转录激活因子之一ETS1的表达，促进了Cldn5基因的转录和BBB的稳定。总的来说，这些研究结果表明，HIIT通过消除HHCY对血脑屏障完整性的破坏性影响来改善慢性压力诱导的认知障碍，为压力相关的认知缺陷提供了一种非药物干预的可能性。

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引用次数: 0

Virtual stress testing: Analyzing endocrine, metabolic, cardiovascular, and psychological responses to the TSST-VR 虚拟压力测试：分析内分泌、代谢、心血管和心理对TSST-VR的反应

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-13 DOI: 10.1016/j.ynstr.2025.100760

Eva Fellinger , Tom Brandt , Andrea Schittenhelm , Eric Quarg , Matthias Pröll , Gregor Domes , Annette Schmidt

Background

The Trier Social Stress Test (TSST) is a widely used tool for inducing and measuring stress responses in a controlled environment. In this study, we aimed to explore the effectiveness of a virtual TSST (TSST-VR) in eliciting stress responses across multiple physiological and psychological markers.

Methods

A sample of 24 participants underwent the TSST-VR, during which salivary cortisol, alpha-amylase (AA), blood glucose levels, heart rate (HR), root mean square of successive differences (RMSSD) as a measure of heart rate variability (HRV), and subjective stress ratings (NRS) were collected at multiple time points.

Results

In a baseline-to-peak analysis, significant increases were observed in HR (M_Diff = 13.04, 95 %-CI [8.19–17.90], p < .001), RMSSD (M_Diff = 17.75, 95 %-CI [3.28–32.22], p < .001), AA (p < .001, r = 1.07), and NRS (p < .001, r = 1.31) measures following the TSST-VR. While no significant changes in cortisol levels were found in the baseline-to-peak analysis across all participants, a secondary cluster analysis identified distinct cortisol responders (baseline-to-peak rise >1.5 mmol/l). Within this group, high cortisol responders (HCR) showed significantly higher cortisol (Wald χ²(7) = 118.03, p < .001), HR (Wald χ²(8) = 17.91, p = .022), and AA levels (Wald χ²(7) = 17.13, p = .017) compared to low cortisol responders (LCR). Area-under-the-curve analysis further confirmed a more robust cortisol stress response in HCR.

Conclusion

These findings suggest that the TSST-VR can effectively induce measurable stress responses and may provide insights into individual differences in physiological and metabolic stress reactions. The study highlights the potential of virtual stress paradigms in stress research and underscores the advantages of a virtual setting in terms of standardization and economic considerations.

Trier社会压力测试（TSST）是一种在受控环境中诱导和测量压力反应的广泛使用的工具。在这项研究中，我们的目的是探讨虚拟TSST （TSST- vr）在多种生理和心理标记中引发应激反应的有效性。方法对24名参与者进行TSST-VR，在此期间，在多个时间点收集唾液皮质醇、α -淀粉酶（AA）、血糖水平、心率（HR）、连续差异均方根（RMSSD）作为心率变异性（HRV）的测量指标，以及主观应激评分（NRS）。结果基线-峰值分析显示，TSST-VR后患者的HR （MDiff = 13.04, 95% -CI [8.19-17.90], p < 0.001）、RMSSD （MDiff = 17.75, 95% -CI [3.28-32.22], p < 0.001）、AA （p < 0.001, r = 1.07）和NRS （p < 0.001, r = 1.31）指标均显著升高。虽然在所有参与者的基线-峰值分析中没有发现皮质醇水平的显著变化，但二次聚类分析确定了不同的皮质醇应答者（基线-峰值升高>；1.5 mmol/l）。在该组中，高皮质醇应答者（HCR）的皮质醇（Wald χ2(7) = 118.03, p < 0.001）、HR （Wald χ2(8) = 17.91, p = 0.022）和AA水平（Wald χ2(7) = 17.13, p = 0.017）均显著高于低皮质醇应答者（LCR）。曲线下面积分析进一步证实了HCR中更强的皮质醇应激反应。结论TSST-VR可有效诱导可测量的应激反应，为揭示生理和代谢应激反应的个体差异提供依据。该研究强调了虚拟应力范式在应力研究中的潜力，并强调了虚拟环境在标准化和经济考虑方面的优势。

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引用次数: 0

Default mode network connectivity contributes the augment effect stress recovery by natural viewing 默认模式的网络连接有助于自然观察应力恢复的增强效应

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-12 DOI: 10.1016/j.ynstr.2025.100759

Zini Chen , Chanyu Wang , Timothea Toulopoulou , Xiayan Chen , Lijing Niu , Haowei Dai , Qingzi Zhu , Yuanyuan Zeng , Ruibin Zhang

The psychological benefits of exposure to natural environments are well established. However, whether simply viewing nature images produce similar restorative effects and the brain mechanisms involved remain unclear. For study purposes, we recruited 131 healthy university students and randomly assigned them to a nature image viewing group (NG) or a city image viewing group (CG), with 49 participants further selected (NG = 26, CG = 23) to undergo functional magnetic resonance imaging while performing behavioral tasks. First, we compared changes in subjective ratings and salivary cortisol levels, related to affect and stress between the NG and CG after stress induction and image viewing. Next, we examined differences in functional connectivity (FC) patterns of the default mode network (DMN) between the groups during image viewing. Finally, we explored correlations between the recovery effects observed after viewing nature images, along with alterations in FC. Under stress, NG participants reported greater changes in subjective ratings of positive affect (t = 2.610, p = 0.010), lower negative affect (t = −3.008, p = 0.003), and less state rumination (t = −2.103, p = 0.037). Neural data also suggest that connectivity of the DMN subsystems with attentional and executive regions plays a crucial role in modulating stress-related responses during natural experiences. Increased FC between the medial DMN subsystem and other networks was significantly correlated with behavioral recovery scores for both affect and state rumination. These findings indicate that viewing images of natural scenes can aid in stress recovery, highlighting the potential for indoor nature viewing to help mitigate psychological challenges faced in urban environments.

暴露在自然环境中的心理益处是公认的。然而，是否仅仅观看自然图像就能产生类似的恢复效果，以及其中涉及的大脑机制尚不清楚。为了研究目的，我们招募了131名健康的大学生，将他们随机分为自然图像观看组（NG）和城市图像观看组（CG），并进一步选择49名参与者（NG = 26, CG = 23）在执行行为任务时进行功能磁共振成像。首先，我们比较了应激诱导和图像观看后NG和CG之间与情绪和压力相关的主观评分和唾液皮质醇水平的变化。接下来，我们检查了两组在图像观看过程中默认模式网络（DMN）的功能连接（FC）模式的差异。最后，我们探讨了在观看自然图像后观察到的恢复效果与FC变化之间的相关性。在压力下，NG参与者报告了积极情绪主观评分的较大变化（t = 2.610, p = 0.010），消极情绪较低（t = - 3.008, p = 0.003），状态反思较少（t = - 2.103, p = 0.037）。神经数据还表明，DMN子系统与注意和执行区域的连通性在自然体验中调节压力相关反应中起着至关重要的作用。内侧DMN子系统与其他网络之间的FC增加与情绪反刍和状态反刍的行为恢复得分显著相关。这些发现表明，观看自然场景的图像可以帮助压力恢复，强调室内自然观看有助于减轻城市环境中面临的心理挑战的潜力。

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引用次数: 0

From intracellular sensors to systemic resilience: Reframing the biology of stress 从细胞内传感器到系统恢复力：重新构建压力生物学

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-09 DOI: 10.1016/j.ynstr.2025.100755

Jakob Hartmann

The biological consequences of chronic stress and trauma are complex, influencing multiple systems and contributing to the development of psychiatric disorders such as MDD and PTSD. Yet, the underlying molecular mechanisms that confer susceptibility in some individuals but resilience in others remain incompletely understood. To help close these knowledge gaps, my work centers on glucocorticoid signaling as a core mechanism underlying stress-related adaptations. This includes the glucocorticoid receptor (GR), its co-chaperones FKBP5 and FKBP4, and regulatory partners such as SKA2. Through a combination of genetic, viral, pharmacological, and transcriptomic approaches, my lab has delineated how these molecules influence HPA axis feedback, fear-related learning, and stress recovery. Recently, we identified a novel, GR-independent role for SKA2 in regulating secretory autophagy, a non-lytic autophagy pathway involved in vesicular cargo release, including cytokine secretion in microglia. These findings established a mechanistic link between intracellular stress signaling and neuroinflammatory responses. In a parallel line of research, we are investigating how chronic stress alters the gut microbiome composition and function, and how these changes impact behavior. Our aim is to harness dietary and probiotic interventions to restore homeostatic balance and enhance stress resilience. By integrating molecular neuroscience with immune and microbiome research, my long-term goal is to build a comprehensive, systems-level model of stress vulnerability and resilience. This approach holds promise for identifying novel biomarkers and therapeutic targets that support mental health and resilience across the lifespan.

慢性应激和创伤的生物学后果是复杂的，影响多个系统，并有助于精神疾病的发展，如重度抑郁症和创伤后应激障碍。然而，在某些个体中赋予易感性而在另一些个体中赋予弹性的潜在分子机制仍然不完全清楚。为了帮助缩小这些知识差距，我的工作集中在糖皮质激素信号作为压力相关适应的核心机制上。这包括糖皮质激素受体（GR），其共同伴侣FKBP5和FKBP4，以及调控伙伴如SKA2。通过基因、病毒、药理学和转录组学方法的结合，我的实验室已经描绘了这些分子如何影响HPA轴反馈、恐惧相关的学习和压力恢复。最近，我们发现了SKA2在调节分泌性自噬中的一种新的、不依赖于gr的作用，这是一种参与小胶质细胞囊泡货物释放的非溶解性自噬途径，包括细胞因子的分泌。这些发现建立了细胞内应激信号和神经炎症反应之间的机制联系。在平行研究中，我们正在研究慢性压力如何改变肠道微生物组的组成和功能，以及这些变化如何影响行为。我们的目标是利用饮食和益生菌干预来恢复体内平衡和增强应激恢复能力。通过将分子神经科学与免疫和微生物组研究相结合，我的长期目标是建立一个全面的、系统级的压力脆弱性和恢复力模型。这种方法有望确定新的生物标志物和治疗靶点，以支持整个生命周期的心理健康和恢复能力。

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引用次数: 0

Transcriptomic profiles of susceptibility and resilience to stress in the amygdala and hippocampus of male rats 雄性大鼠杏仁核和海马体对应激的易感性和恢复力的转录组学特征

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-09-01 DOI: 10.1016/j.ynstr.2025.100754

Kimberly L.P. Long , Sandra E. Muroy , Siamak K. Sorooshyari , Mee Jung Ko , Yanabah Jaques , Kishant Mohan , Peter Sudmant , Daniela Kaufer

Traumatic experiences elicit a wide range of cognitive responses in both humans and animals, leading to diverse outcomes such as enhanced performance, cognitive impairment, or the development of mood and anxiety disorders like posttraumatic stress disorder (PTSD). A key challenge in understanding these varied responses is to decipher the underlying biological mechanisms that contribute to individual variability in trauma resilience or susceptibility. The purpose of this study was to elucidate the molecular bases for these differences, focusing on the amygdala and hippocampus—brain regions integral to stress responses. We exposed adult, male rats to an acute, severe stressor and profiled persistent anxiety-like behavior outcomes 7 days later. We investigated the transcriptional signatures in the basolateral amygdala and hippocampal dentate gyrus via bulk RNA sequencing from animals with behavioral outcomes indicative of stress resilience or vulnerability. Our results suggest that the basolateral amygdala and dentate gyrus display distinct transcriptomic changes following acute, severe stress. Furthermore, we identified specific region-dependent genes related to insulin signaling, neural plasticity, and stress responses that correlate with resilient and vulnerable phenotypes. Notably, a larger number of genes separated stress-resilient animals from both control and stress-susceptible animals, underscoring that an active molecular response, particularly in the hippocampus, facilitates protection from the long-term consequences of severe stress. These findings provide novel insight into the mechanisms that engender individual variability in the behavioral responses to stress and offer new targets for the advancement of therapies for stress-induced neuropsychiatric disorders.

创伤经历在人类和动物中引起广泛的认知反应，导致不同的结果，如表现增强、认知障碍或情绪和焦虑障碍的发展，如创伤后应激障碍（PTSD）。理解这些不同的反应的一个关键挑战是破译导致创伤恢复力或易感性个体差异的潜在生物学机制。本研究的目的是阐明这些差异的分子基础，重点研究杏仁核和海马体-大脑区域对应激反应的影响。我们将成年雄性大鼠暴露在急性、严重的压力源中，并在7天后对持续的焦虑样行为结果进行了分析。我们通过大量RNA测序研究了基底外侧杏仁核和海马齿状回的转录特征，这些转录特征来自具有应激恢复力或脆弱性行为结果的动物。我们的研究结果表明，基底外侧杏仁核和齿状回在急性严重应激后表现出明显的转录组变化。此外，我们确定了与胰岛素信号、神经可塑性和应激反应相关的特定区域依赖基因，这些基因与弹性和脆弱表型相关。值得注意的是，大量的基因将应激恢复动物与对照动物和应激易感动物分开，强调活跃的分子反应，特别是在海马体中，有助于保护动物免受严重应激的长期后果。这些发现为应激行为反应的个体差异机制提供了新的见解，并为应激性神经精神疾病的治疗提供了新的靶点。

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引用次数: 0

Interactive effects of early life adversity and adolescent basolateral amygdala activity on corticolimbic connectivity and behavior 早期生活逆境和青少年基底外侧杏仁核活动对皮质边缘连通性和行为的交互影响

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-08-20 DOI: 10.1016/j.ynstr.2025.100753

Caitlyn R. Cody , Emilce Artur de la Villarmois , Anabel M.M. Miguelez Fernández , Janelle P. Lardizabal , Kuei Y. Tseng , Heather C. Brenhouse

Corticolimbic development is shaped by the environment and relies on coordinated neuronal activity. Prior work revealed that early life adversity (ELA) leads to hyperinnervation of basolateral amygdala (BLA) projections to the prefrontal cortex (PFC) beginning in early adolescence. Both ELA and corticolimbic hyperconnectivity are associated with anxiety-like behavior, however the underlying developmental processes driving these effects are largely unknown. Here we investigated interactive impacts of rearing environment and neuronal activity on behavior and corticolimbic connectivity in rats. We first found that BLA-PFC hyperinnervation was associated with enhanced BLA-evoked PFC local field potentials in adolescents exposed to maternal separation (MS) ELA. Since ELA reportedly increases activity in the early-developing BLA, we further examined whether reducing BLA activity during adolescence influences behavior or enduring PFC innervation. During early adolescence, MS animals displayed heightened exploratory behaviors in an open field. Differences between rearing groups were not present during acute inhibition of glutamatergic BLA neurons, as BLA inhibition resembled the effects of MS on adolescent exploratory behaviors. To examine longer-lasting impacts of adolescent BLA activity on PFC innervation, BLA-originating axonal boutons were quantified in the PFC during emerging adulthood after adolescent BLA inhibition. We expanded previous findings to show that MS causes enduring BLA-PFC hyperinnervation. Surprisingly, adolescent BLA inhibition itself increased BLA-PFC innervation in control animals, suggesting that hyperpolarization of output neurons during early adolescence may contribute to aberrant development of efferent projections. Taken together, our results indicate that ELA yields increased BLA-PFC innervation in adulthood that may involve enhanced inhibitory signaling within developing BLA circuitry.

皮质边缘的发育受环境影响，依赖于协调的神经元活动。先前的研究表明，早期生活逆境（ELA）导致青春期早期开始的基底外侧杏仁核（BLA）向前额皮质（PFC）投射的神经支配过度。ELA和皮质边缘超连通性都与焦虑样行为有关，然而驱动这些影响的潜在发育过程在很大程度上是未知的。本研究探讨了饲养环境和神经元活动对大鼠行为和皮质边缘连通性的交互影响。我们首先发现，暴露于母亲分离（MS） ELA的青少年中，BLA-PFC神经过度分布与bla诱发的PFC局部场电位增强有关。由于据报道ELA增加了早期发育的BLA的活动，我们进一步研究了青春期BLA活动的减少是否会影响行为或持久的PFC神经支配。在青春期早期，多发性硬化症动物在开放领域表现出更高的探索行为。在谷氨酸能BLA神经元的急性抑制中，饲养组之间不存在差异，因为BLA抑制类似于MS对青少年探索行为的影响。为了研究青少年BLA活性对PFC神经支配的长期影响，在青少年BLA抑制后的成年期，对PFC中起源于BLA的轴突钮扣进行了量化。我们扩展了先前的研究结果，表明MS导致持久的BLA-PFC神经过度支配。令人惊讶的是，青春期BLA抑制本身增加了对照动物的BLA- pfc神经支配，这表明青春期早期输出神经元的超极化可能导致传出投射的异常发育。综上所述，我们的研究结果表明，ELA在成年期增加了BLA- pfc神经的支配，这可能涉及BLA回路中抑制信号的增强。

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引用次数: 0

Sexual dimorphism in anxiety susceptibility: role of PNN maturation timing in the habenulo-interpeduncular reward circuits 焦虑易感性中的两性二态性：PNN成熟时间在habenul - interpotic奖赏回路中的作用

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-08-17 DOI: 10.1016/j.ynstr.2025.100750

Niels Fjerdingstad, Malalaniaina Rakotobe , Célia Leboulenger, Adrien Chopin, Thomas Lamonerie, Fabien D'Autréaux

引用次数: 0

Cardiometabolic and anxiogenic consequences of chronic social defeat stress in male mice 雄性小鼠慢性社会失败应激的心脏代谢和焦虑后果

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-08-13 DOI: 10.1016/j.ynstr.2025.100752

Karen A. Scott , Sophia A. Eikenberry , Khalid Elsaafien , Caitlin Baumer-Harrison , Dominique N. Johnson , Jéssica Matheus Sá , Alessandro Bartolomucci , Colin Sumners , Eric G. Krause , Annette D. de Kloet

Social adversity, such as that which occurs during subjugation to a lower social status, has profound psychological and cardiometabolic consequences that are conserved across species. Clinically, such adversity often arises from being of a lower socioeconomic status and may contribute to health disparities in cardiometabolic and affective disorders. To develop a better understanding of the cardiometabolic consequences of social adversity, we employ chronic social defeat stress (CSDS) in adult male mice. CSDS results in increases in body mass, that are accompanied by elevated lean and fluid mass, as well as several somatic indices of chronic stress. Moreover, mice exposed to CSDS exhibit increased anxiety-like behavior, spending more time in the closed arms of the elevated plus maze and less time in the center of an open field arena. Regarding cardiovascular parameters, initial social defeat sessions result in increases in blood pressure, activity, and temperature in comparison with control mice. Interestingly, while blood pressure returns to basal levels by the start of the light cycle for the first few days of defeat, 14 days of CSDS results in sustained elevations in blood pressure, lower activity and lower body temperature. Finally, the results of heart rate variability, spontaneous baroreflex sensitivity and adrenal transcriptome analyses were consistent with CSDS-induced autonomic dysfunction, effects that may contribute to the hypertension observed. Collectively, these data suggest that CSDS may be useful for modeling hypertension induced by chronic social stress, thereby enabling us to better understand the mechanisms that contribute to stress-induced cardiometabolic disease.

社会逆境，比如在社会地位低下时发生的逆境，具有深远的心理和心脏代谢影响，这种影响在物种中是保守的。在临床上，这种逆境往往源于较低的社会经济地位，并可能导致心脏代谢和情感疾病的健康差异。为了更好地理解社会逆境对心脏代谢的影响，我们在成年雄性小鼠中使用了慢性社会失败压力（CSDS）。CSDS导致体重增加，并伴有瘦肉和液体质量升高，以及一些慢性应激的躯体指标。此外，暴露于CSDS的小鼠表现出更多的焦虑样行为，在高架+迷宫的封闭手臂中花费更多的时间，而在开放场地中心的时间更少。在心血管参数方面，与对照组小鼠相比，最初的社交失败会导致血压、活动和体温升高。有趣的是，虽然在失败的最初几天，血压会在光周期开始时恢复到基础水平，但14天的CSDS会导致血压持续升高，活动减少和体温降低。最后，心率变异性、自发性压力反射敏感性和肾上腺转录组分析的结果与csds诱导的自主神经功能障碍一致，这些影响可能有助于观察到的高血压。综上所述，这些数据表明CSDS可能对慢性社会压力诱导的高血压建模有用，从而使我们能够更好地理解压力诱导的心脏代谢疾病的机制。

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引用次数: 0

Not just a witness: Highlighting the utility of witness social defeat stress for the examination of neuroimmune-cardiovascular interactions across diverse populations 不仅仅是一个证人：强调证人社会失败压力在不同人群中神经免疫-心血管相互作用检查中的效用

IF 3.6 2区医学 Q1 NEUROSCIENCES

Neurobiology of Stress

Pub Date : 2025-08-12 DOI: 10.1016/j.ynstr.2025.100751

Margherita Barbetti , Cora E. Smiley , Monia Savi , Andrea Sgoifo , Susan K. Wood , Luca Carnevali

Exposure to stress has widespread pathological consequences in terms of neuropsychiatric disorders and cardiovascular disease. Psychosocial stressors represent the most highly impactful and commonly experienced form of stress and, in preclinical studies, have been found to induce distinct overlapping immune and cardiovascular alterations. Historically, the social defeat model has been fundamental in providing insights into the autonomic and neuroimmune mediators of cardiovascular dysfunction in the face of social stress exposure. However, this procedure relies on aggressive, physical interaction between rodents and is limited by its almost exclusive application to young adult males. This challenges the possibility of using social defeat to generate data in rodents that can be translated into social stress-related processes in both men and women across the lifespan. More recently, a novel vicarious social defeat procedure has been developed, wherein a rodent bears witness to an aggressive social defeat encounter between two males from the safety of an adjacent compartment. This review first discusses the existing data regarding stress-induced cardiovascular alterations and the underlying autonomic and neuroimmune mediators of social defeat while critically discussing the limitations of this model. New prospects are then offered based on recent findings across a diverse population of rodent species, sexes, and ages to support the use of vicarious/witness social defeat model as an optimal strategy to investigate social stress-related autonomic, neuroimmune, and cardiovascular processes using more comprehensive and inclusive methods.

暴露于压力在神经精神疾病和心血管疾病方面具有广泛的病理后果。心理社会压力源是最具影响力和最常见的压力形式，在临床前研究中，已发现可诱导明显重叠的免疫和心血管改变。从历史上看，社会失败模型在提供面对社会压力暴露时心血管功能障碍的自主神经和神经免疫介质的见解方面是基础的。然而，这种方法依赖于啮齿动物之间的攻击性身体相互作用，并且几乎只适用于年轻的成年雄性，因此受到限制。这挑战了利用社会失败在啮齿动物中产生数据的可能性，这些数据可以转化为男性和女性一生中与社会压力相关的过程。最近，一种新的替代性社会失败程序被开发出来，其中一只啮齿动物从相邻的安全隔间见证了两只雄性动物之间的攻击性社会失败遭遇。这篇综述首先讨论了关于压力诱导的心血管改变和潜在的自主神经和神经免疫介质的现有数据，同时批判性地讨论了该模型的局限性。基于最近对不同啮齿动物种群、性别和年龄的研究结果，研究人员提供了新的前景，以支持将替代/见证社会失败模型作为一种最佳策略，使用更全面和包容的方法来研究与社会压力相关的自主神经、神经免疫和心血管过程。

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