Brain, behavior, & immunity - health最新文献_第5页

Gestational stress disrupts the neuroimmune environment in the nucleus accumbens of maternal rats 妊娠应激破坏母鼠伏隔核的神经免疫环境

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101140

Courtney N. Dye , Dominic V. Franceschelli , Caitlin Goodpaster , Lynde M. Wangler , Amanda Ringland , Jonathan P. Godbout , Kathryn M. Lenz , Benedetta Leuner

Postpartum depression (PPD) affects 20 % of new mothers. Little is known about what contributes to this prevalence, though one of the strongest risk factors for developing PPD is stress during pregnancy. Pregnancy and the postpartum period are accompanied by dramatic changes in the endocrine, nervous, and immune systems, which may confer heightened vulnerability to maternal mental illness. Microglia, the brain's main immune cells, are important for displaying maternal behaviors. Environmental insults to microglia, such as stress, lead to hormonal dysregulation and aberrant synaptic pruning, both of which have been implicated in the pathophysiology of mood disorders like depression. Given these links, we hypothesized that stress during pregnancy would lead to dysregulated neuroimmune and endocrine profiles and produce synaptic changes in the maternal brain. We used a 2-week variable stress model in pregnancy and assessed neuroimmune changes in the nucleus accumbens (NAc), a brain region that regulates functions impaired in PDD including mood and maternal caregiving. Peripheral hormones and cytokines were also measured. While peripheral cytokine levels were not affected by stress exposure, gestational stress induced central immune changes in the NAc of maternal rats. This included increased microglia immunolabeling and changes in pro- and anti-inflammatory transcripts measured by a Nanostring nCounter panel. Astrocytes also increased in the NAc following gestational stress exposure. Peripheral estradiol and progesterone concentrations were reduced in late pregnancy of stressed mothers, and at the transcript level, hormone receptor and synthesis molecules were altered in the NAc. Gestational stress also altered transcripts associated with synapses and synaptic plasticity during late pregnancy and the postpartum period. There was no impact of stress on engulfment of pre- and postsynaptic proteins by microglia. However, microglia engulfed more of the postsynaptic marker, PSD95, in late pregnancy relative to postpartum, indicating a potential role for microglia in remodeling synapses in the NAc. Overall, these studies provide novel evidence that gestational stress impacts endocrine, synaptic and neuroimmune factors in the maternal NAc, suggesting possible mechanisms by which stress during pregnancy contributes to peripartum mood disorders.

产后抑郁症（PPD）影响了20%的新妈妈。尽管怀孕期间的压力是诱发产后抑郁症的最大风险因素之一，但人们对导致这种患病率的原因知之甚少。怀孕和产后期间伴随着内分泌、神经和免疫系统的剧烈变化，这可能使产妇更容易患精神疾病。小胶质细胞是大脑的主要免疫细胞，对母性行为的表现很重要。环境对小胶质细胞的损害，如压力，会导致激素失调和突触修剪异常，这两者都与抑郁症等情绪障碍的病理生理学有关。鉴于这些联系，我们假设怀孕期间的压力会导致神经免疫和内分泌失调，并在母体大脑中产生突触变化。我们在怀孕期间使用了一个2周的可变压力模型，并评估了伏隔核（NAc）的神经免疫变化，这是一个调节PDD功能受损的大脑区域，包括情绪和母亲照顾。外周激素和细胞因子也被测量。外周细胞因子水平不受应激暴露的影响，但妊娠应激诱导母鼠NAc中枢免疫发生变化。这包括增加的小胶质细胞免疫标记和通过Nanostring nCounter面板测量的促抗炎转录物的变化。妊娠应激暴露后NAc中的星形胶质细胞也增加。应激母亲妊娠后期外周血雌二醇和孕酮浓度降低，在转录水平上，NAc中的激素受体和合成分子发生改变。妊娠应激也改变了与突触和突触可塑性相关的转录本在妊娠后期和产后时期。应激对小胶质细胞吞噬突触前蛋白和突触后蛋白没有影响。然而，与产后相比，妊娠后期小胶质细胞吞噬了更多的突触后标记物PSD95，这表明小胶质细胞在NAc突触重塑中的潜在作用。总之，这些研究提供了新的证据，表明妊娠应激影响母体NAc的内分泌、突触和神经免疫因子，提示妊娠应激导致围产期情绪障碍的可能机制。

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引用次数: 0

Leveraging microbiota-metabolites to reduce inflammation and promote functional recovery following spinal cord injury in female mice 利用微生物代谢物减少雌性小鼠脊髓损伤后的炎症和促进功能恢复

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101157

Ashley J. Douthitt , Aaron Bennett , Alexandra Koustova , Asim Abdelfattah , Darijana Horvat , Cédric G. Geoffroy

Spinal cord injury induces extensive neurological impairment and drives systemic and tissue-level inflammatory responses that accelerate secondary systemic damage. Emerging evidence suggests that gut microbiota-derived metabolites can influence post-injury inflammation, presenting a potential therapeutic approach. This study examines whether the tryptophan-derived metabolites indole and indole-3-propionic acid modulate inflammatory responses and improve outcomes following spinal cord injury. Female C57BL/6J mice received a severe thoracic-8 contusion-compression injury and were administered indole or indole-3-proprionic acid daily via oral gavage for the duration of the observation period. In an acute cohort, 7 days post-injury, neither treatment altered plasma inflammatory profiles relative to injury controls. However, both metabolites significantly reduced CD68⁺ macrophage presence within the injured spinal cord. In a chronic cohort, 42 days post-injury, metabolite treatment mitigated injury-induced body composition changes, improved locomotor recovery and reduced inflammatory pathologies within the liver and spinal cord. These findings identify gut-derived metabolites as a promising therapeutic strategy targeting the gut-spinal cord axis to attenuate systemic injury mechanisms and support recovery.

脊髓损伤引起广泛的神经损伤，并驱动全身和组织水平的炎症反应，加速继发性全身损伤。新出现的证据表明，肠道微生物衍生的代谢物可以影响损伤后炎症，提出了一种潜在的治疗方法。本研究探讨了色氨酸衍生的代谢物吲哚和吲哚-3-丙酸是否能调节脊髓损伤后的炎症反应并改善预后。雌性C57BL/6J小鼠重度胸-8挫伤压缩损伤，观察期间每天灌胃吲哚或吲哚-3-本体酸。在一个急性队列中，损伤后7天，两种治疗都没有改变相对于损伤对照组的血浆炎症谱。然而，这两种代谢物显著降低了受损脊髓内CD68+巨噬细胞的存在。在一个慢性队列中，损伤后42天，代谢物治疗减轻了损伤引起的身体成分变化，改善了运动恢复，减少了肝脏和脊髓内的炎症病理。这些发现确定了肠道衍生代谢物作为一种有希望的治疗策略，靶向肠-脊髓轴，以减轻全身损伤机制并支持恢复。

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引用次数: 0

Immune dysregulation and neuroinflammation in bipolar disorder: Pathophysiological insights and therapeutic perspectives 双相情感障碍的免疫失调和神经炎症：病理生理学见解和治疗观点

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101155

Floriana De Cillis , Veronica Begni , Ilari D'Aprile , Giulia Petrillo , Marco Andrea Riva , Annamaria Cattaneo

Bipolar disorder (BD) is increasingly associated with immune system dysregulation encompassing both peripheral and central components. Peripheral low-grade inflammation, marked by elevated proinflammatory cytokines and impaired anti-inflammatory responses, contributes to systemic immune imbalance in BD. This peripheral inflammatory state may compromise blood–brain barrier (BBB) integrity, facilitating the entry of peripheral immune mediators into the central nervous system (CNS) and triggering neuroinflammatory cascades. Within the CNS, neuroinflammation is orchestrated primarily by microglial and astrocytic activation, which disrupts neuronal homeostasis and synaptic function. Additionally, oxidative stress acts as a crucial mediator, exacerbating neuronal damage. Based on current findings, this review synthesises evidence linking both central and peripheral inflammation to the pathophysiology of BD, offering a perspective on its underlying biology. A comprehensive understanding of the dynamic interplay between peripheral inflammation and central neuroimmune responses is essential for identifying novel therapeutic targets and developing interventions that effectively address both systemic and CNS components of BD pathophysiology.

双相情感障碍（BD）越来越多地与免疫系统失调有关，包括外周和中枢成分。外周低级别炎症，以促炎细胞因子升高和抗炎反应受损为特征，导致BD的全身免疫失衡。这种外周炎症状态可能破坏血脑屏障（BBB）的完整性，促进外周免疫介质进入中枢神经系统（CNS）并引发神经炎症级联反应。在中枢神经系统内，神经炎症主要是由小胶质细胞和星形胶质细胞激活引起的，这破坏了神经元的稳态和突触功能。此外，氧化应激作为一个重要的中介，加剧了神经元损伤。基于目前的研究结果，本综述综合了将中枢和外周炎症与双相障碍的病理生理联系起来的证据，为其潜在的生物学提供了一个视角。全面了解外周炎症和中枢神经免疫反应之间的动态相互作用，对于确定新的治疗靶点和开发有效解决双相障碍病理生理系统和中枢神经系统成分的干预措施至关重要。

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引用次数: 0

Effects of palmitoylethanolamide in clinical high-risk for psychosis: A nonrandomized open-label trial 棕榈酰乙醇酰胺在临床精神病高危患者中的作用：一项非随机开放标签试验

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101141

Riccardo Bortoletto , Marco Garzitto , Marta Basaldella , Claudia Scipioni , Orietta Sepulcri , Martina Fabris , Francesco Curcio , Matteo Balestrieri , Marco Colizzi

Clinical high-risk (CHR) for psychosis state still lacks effective and safe treatments. Recent evidence supports the anti-neuroinflammatory properties of fatty acid palmitoylethanolamide (PEA) dietary supplementation across the psychosis spectrum. Sixteen subjects at CHR for psychosis with attenuated psychotic symptoms (APS) enrolled in a 12-week, open-label, nonrandomized, single-arm clinical trial of ultramicronized-PEA (um-PEA, 600 mg/day). Biobehavioral assessments were conducted at baseline, 4 weeks, and 12 weeks, particularly using the Comprehensive Assessment of At-Risk Mental States (CAARMS) and quantifying changes in peripheral neuroimmune biomarkers. Linear mixed-effects models showed significant reductions in CAARMS total APS (Δ_12-weeks = −3.8 units, −30.0 %) and Unusual Thought Content (UTC; Δ_12-weeks = −2.0, −52.5 %). No treatment-emergent side effects were reported. In exploratory analyses including neuroimmune biomarkers as covariates and potential moderators, lower baseline Interleukin (IL)-1β was associated with greater improvement in UTC, while time-varying IL-10/IL-6 ratio, Interferon (IFN)-γ, and IL-6 were linked to changes in CAARMS total APS and UTC.

A reduction in APS was observed in subjects at CHR for psychosis receiving PEA supplementation, possibly through immune-inflammatory modulation, warranting further research into its therapeutic potential for this condition.

Trial registration

ClinicalTrials.gov Identifier NCT06037993.

临床高危（CHR）精神状态仍然缺乏有效和安全的治疗方法。最近的证据支持脂肪酸棕榈酰乙醇酰胺（PEA）膳食补充剂在精神病谱系中的抗神经炎症特性。16名在CHR接受精神病症状减轻（APS）治疗的患者参加了一项为期12周、开放标签、非随机、单组的超微化pea （um-PEA， 600 mg/天）临床试验。在基线、4周和12周进行生物行为评估，特别是使用危险精神状态综合评估（CAARMS）和量化周围神经免疫生物标志物的变化。线性混合效应模型显示CAARMS总APS （Δ12-weeks =−3.8个单位，−30.0%）和异常思维含量（UTC； Δ12-weeks =−2.0,−52.5%）显著降低。无治疗后出现的副作用报告。在包括神经免疫生物标志物作为协变量和潜在调节因子的探索性分析中，较低的基线白介素(IL)-1β与UTC的更大改善有关，而随时间变化的IL-10/IL-6比率、干扰素(IFN)-γ和IL-6与CAARMS总APS和UTC的变化有关。在CHR接受PEA补充治疗的精神病患者中，观察到APS的减少，可能是通过免疫炎症调节，值得进一步研究其治疗这种疾病的潜力。试验注册clinicaltrials .gov标识符NCT06037993。

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引用次数: 0

Immune and metabolic disturbance as a function of genetic risk and phase of illness in major depression 重性抑郁症患者的免疫和代谢紊乱与遗传风险和疾病阶段的关系

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101144

David M. Howard , Lachlan Gilchrist , Petroula Proitsi , Elisabeth R. Paul , Markus Heilig , Lars Östman , Robin Kämpe , J. Paul Hamilton

Immune and metabolic factors are important in the pathophysiology of major depressive disorder (MDD) but we know little about how these factors manifest in relation to the status of depressive illness—from genetic risk for MDD, to a depressive episode, to depression in remission. Using genetic, diagnostic, biometric, and blood-bioassay data from the UK Biobank, we examined measures of pro-inflammatory signaling (C-reactive protein) and metabolic dysfunction (metabolic syndrome symptomatology) in females (N = 37,806) and males (N = 17,946) as a function of polygenic load for MDD (high versus low) interacting with depression status (never depressed, currently depressed, or depression in remission). We examined socioeconomic status (SES) as an exploratory factor in this design. Groups were matched for several confounders using a propensity-matching algorithm (females: n = 6301 per group for N = 37,806; n = 2991 per group for N = 17,946). In females we found increased inflammation and metabolic dysfunction in the higher-versus-lower PRS quartile, in those below-versus-above the median SES, and in those suffering currently from depression relative to their remitted depressed and healthy counterparts. This association remained when considering only non-psychotropic-medicated persons. Nonetheless, we also saw in both male and female samples that measures of immunological and metabolic dysfunction increased with increasing anti-depressant medication load. We discuss these findings in terms of the epidemiological significance of immune and metabolic functioning in depression and their paradoxical relation with antidepressant treatment.

免疫和代谢因素在重度抑郁症（MDD）的病理生理学中很重要，但我们对这些因素如何表现与抑郁症状态的关系知之甚少-从MDD的遗传风险到抑郁发作，再到抑郁缓解期。使用来自UK Biobank的遗传、诊断、生物计量和血液生物测定数据，我们检测了女性（N = 37,806）和男性（N = 17,946）的促炎信号（c反应蛋白）和代谢功能障碍（代谢综合征症状学）作为MDD多基因负荷（高与低）与抑郁状态（从未抑郁、目前抑郁或抑郁缓解）相互作用的功能。我们将社会经济地位（SES）作为本设计的探索性因素。使用倾向匹配算法对几个混杂因素进行分组匹配（女性：n = 37,806，每组n = 6301; n = 17,946，每组n = 2991）。在女性中，我们发现在PRS高四分位数与低四分位数、低于SES中位数与高于SES中位数、以及目前患有抑郁症的女性中，炎症和代谢功能障碍的增加与抑郁缓解和健康的女性相比。当只考虑非精神药物患者时，这种关联仍然存在。尽管如此，我们还发现，在男性和女性样本中，免疫和代谢功能障碍的测量值随着抗抑郁药物负荷的增加而增加。我们从免疫和代谢功能在抑郁症中的流行病学意义以及它们与抗抑郁药物治疗的矛盾关系的角度讨论这些发现。

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引用次数: 0

Altered brain tissue microstructure and neurochemical profiles in long COVID and recovered COVID-19 individuals: A multimodal MRI study 长期COVID-19和康复COVID-19患者脑组织微观结构和神经化学特征的改变：一项多模态MRI研究

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101142

Kiran Thapaliya, Sonya Marshall-Gradisnik, Maira Inderyas, Leighton Barnden

Background

Diverse neurological symptoms are experienced by long COVID and COVID-19 recovered individuals. However, the long-term effects of SARS-CoV-2 in the brain of both groups are underexplored. This study aimed to investigate changes in tissue microstructural and brain neurochemical levels in long COVID and recovered COVID-19 patients compared to healthy controls.

Methods

We recruited 47 participants (long COVID = 19, COVID-recovered healthy controls = 12, and healthy controls without COVID-19 infection = 16) who underwent 3T MRI scans. We acquired T1 and T2 weighted images to assess myelin signal, diffusion weighted images to assess tissue microstructure, and magnetic resonance spectroscopy data to estimate brain neurochemical levels.

Findings

Our multimodal MRI study showed altered T1w/T2w signal between long COVID vs COVID-recovered-healthy controls, long COVID vs healthy controls, and COVID-recovered-healthy controls vs healthy controls. Furthermore, T1w/T2w signal intensity was significantly correlated with physical and cognitive function. Diffusion weighted imaging also showed altered tissue microstructure in these three group comparisons. However, brain neurochemicals were only significantly different between long COVID vs COVID-recovered-healthy controls.

Interpretation

This is one of the first studies to report different myelin signal and brain neurochemical changes between long COVID, COVID-recovered-healthy controls, and healthy controls without SARS-CoV-2 infection. These brain changes provide compelling evidence for the long-term effects of SARS-CoV-2 on brain function.

长期感染COVID和COVID-19康复的个体会经历多种神经系统症状。然而，SARS-CoV-2对两组大脑的长期影响尚未得到充分探索。本研究旨在探讨COVID-19长期和康复患者与健康对照组相比组织显微结构和脑神经化学水平的变化。方法我们招募了47名参与者（长期COVID = 19， COVID-19康复的健康对照组= 12，未感染COVID-19的健康对照组= 16）进行3T MRI扫描。我们获得T1和T2加权图像来评估髓磷脂信号，扩散加权图像来评估组织微观结构，磁共振波谱数据来评估大脑神经化学物质水平。我们的多模态MRI研究显示，长时间COVID与COVID恢复的健康对照组、长时间COVID与健康对照组、COVID恢复的健康对照组与健康对照组之间的T1w/T2w信号发生了变化。此外，T1w/T2w信号强度与身体和认知功能显著相关。弥散加权成像也显示这三组比较的组织微观结构改变。然而，大脑神经化学物质仅在长期COVID和COVID恢复的健康对照组之间存在显着差异。这是首批报道长期COVID、COVID恢复健康对照组和未感染SARS-CoV-2的健康对照组之间髓磷脂信号和脑神经化学变化的研究之一。这些大脑变化为SARS-CoV-2对大脑功能的长期影响提供了令人信服的证据。

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引用次数: 0

Socio-environmental and health-related factors and their association with longitudinal change in brain neuroimaging markers through the plasma metabolome among UK adults: An additive Bayesian network analysis 社会环境和健康相关因素及其与英国成年人血浆代谢组脑神经成像标志物纵向变化的关联：加性贝叶斯网络分析

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101152

May A. Beydoun , Jordan Weiss , Michael F. Gerogescu , Jason Ashe , Christian A. Maino Vieytes , Tianyi Huang , Hind A. Beydoun , Nicole Noren Hooten , Indira C. Turney , Michele K. Evans , Alan B. Zonderman

Socio-environmental and health-related variables were examined in relation to longitudinal change in select neuroimaging markers through metabolomics. Data from 2255 dementia-free UK Biobank participants were utilized. Statistical analyses involved descriptives, Principal Components Analysis (PCA) for metabolomic data reduction, mixed-effects linear regression models to assess longitudinal change (i.e. empirical Bayes estimators of slope), and Additive Bayesian Networks (ABN). Age was the primary consistent contributor to brain health decline over time, with specific metabolomic markers, mainly “free cholesterol in very large high-density lipoproteins (HDL)”, potentially offering protective effects against declines in microstructural integrity, through reduction of or slower pace of increase in mean Orientation Dispersion (OD_mean). Air pollution, individual and household-level SES, sex and racial minority status correlated indirectly with brain health through intracranial volumes and time interval between assessments. These insights emphasize using a multifactorial approach to understanding brain aging for predictive models of neurodegeneration.

通过代谢组学研究了社会环境和健康相关变量与选择的神经影像学标志物的纵向变化的关系。数据来自2255名无痴呆的英国生物银行参与者。统计分析包括描述性分析、用于代谢组学数据还原的主成分分析（PCA）、用于评估纵向变化的混合效应线性回归模型（即斜率的经验贝叶斯估计器）和加性贝叶斯网络（ABN）。随着时间的推移，年龄是导致大脑健康状况下降的主要因素，具有特定的代谢组学标记，主要是“非常大的高密度脂蛋白（HDL）中的游离胆固醇”，可能通过减少或减缓平均取向弥散（ODmean）的增加速度，对微结构完整性下降提供保护作用。空气污染、个人和家庭经济地位、性别和少数民族地位通过颅内容量和评估间隔时间间接与脑健康相关。这些见解强调使用多因素方法来理解神经变性预测模型的大脑衰老。

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引用次数: 0

Body talk: Correlates of gut-immune dysregulation phenotypes in people living with HIV who use methamphetamine 身体谈话：使用甲基苯丙胺的艾滋病毒感染者肠道免疫失调表型的相关关系

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101156

Wilson Vincent , Annesa Flentje , Benjamin S. Dominguez , Robert H. Paul , Savita Pahwa , Suresh Pallikkuth , Margaret Roach , Dietmar Fuchs , Samantha E. Dilworth , Torsten B. Neilands , Peter W. Hunt , Gowri Sunder , Cody Lentz , Sydney Telaak , Adam W. Carrico

Background

Microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors are interacting pathophysiologic processes linked to neuropsychiatric comorbidities and faster HIV disease progression. We examined correlates of distinct phenotypes of gut-immune dysregulation in people living with HIV (PWH) who use methamphetamine.

Methods

Participants were 122 PWH who had biochemically confirmed recent methamphetamine use, including non-injection use. Peripheral plasma markers reflected: intestinal permeability, microbial translocation, immune activation, inflammation, and dysregulated metabolism of neurotransmitter precursors. Using latent profile analysis (i.e., clustering) of these markers, we identified gut-immune phenotypes and their clinical, demographic, and stigma-related correlates.

Results

Three immune profiles emerged: (1) low gut-immune dysregulation with lower microbial translocation, macrophage activation, inflammation, and tryptophan catabolism; (2) moderate gut-immune dysregulation with all markers within average range; and (3) high gut-immune dysregulation with higher microbial translocation, immune activation, inflammation, and tryptophan catabolism. In adjusted analyses, higher viral load (one log10 copy/ml; AOR = 1.97, 95 % CI = 1.02–3.82), injection of methamphetamine (AOR = 3.60, 95 % CI = 1.23–10.50), and internalized stigma (AOR = 1.78, 95 % CI = 1.01–3.15) were associated with having a moderate gut-immune dysregulation profile. Additionally, higher viral load (AOR = 2.98, 95 % CI = 1.53–5.24) and injecting methamphetamine (AOR = 5.45, 95 % CI = 1.34–17.78) were associated with having a high gut-immune dysregulation profile.

Conclusions

Distinct patterns of microbial translocation, immune activation, inflammation, and metabolism of amino acid precursors distinguished gut-immune phenotypes of PWH reporting injection methamphetamine use and greater internalized stigma. Interventions tailored to PWH who inject methamphetamine or struggle with internalized stigma could optimize HIV-related health outcomes.

微生物易位、免疫激活、炎症和神经递质前体代谢失调是与神经精神合并症和更快的HIV疾病进展相关的相互作用的病理生理过程。我们研究了使用甲基苯丙胺的HIV感染者（PWH）肠道免疫失调的不同表型的相关性。方法研究对象为122名生物化学证实近期使用甲基苯丙胺（包括非注射使用）的PWH。外周血浆标志物反映：肠道通透性、微生物易位、免疫激活、炎症和神经递质前体代谢失调。利用这些标记物的潜在特征分析（即聚类），我们确定了肠道免疫表型及其临床、人口统计学和耻感相关因素。结果出现了三种免疫特征：(1)低肠道免疫失调，微生物易位、巨噬细胞激活、炎症和色氨酸分解代谢降低；(2)中度肠道免疫失调，各项指标均在平均范围内；(3)肠道免疫高度失调，微生物易位、免疫激活、炎症和色氨酸分解代谢增加。在校正分析中，较高的病毒载量（1 log10拷贝/ml； AOR = 1.97, 95% CI = 1.02-3.82）、注射甲基苯丙胺（AOR = 3.60, 95% CI = 1.23-10.50）和内化病耻感（AOR = 1.78, 95% CI = 1.01-3.15）与中度肠道免疫失调相关。此外，较高的病毒载量（AOR = 2.98, 95% CI = 1.53-5.24）和注射甲基苯丙胺（AOR = 5.45, 95% CI = 1.34-17.78）与较高的肠道免疫失调相关。结论不同的微生物易位、免疫激活、炎症和氨基酸前体代谢模式区分了PWH报告注射甲基苯丙胺的肠道免疫表型和更大的内化耻感。针对注射甲基苯丙胺或与内在耻辱作斗争的PWH量身定制的干预措施可以优化与艾滋病毒相关的健康结果。

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引用次数: 0

Glial activation and increase in cerebral pro-inflammatory cytokine expression in a female animal post-COVID model 雌性动物新冠肺炎后模型中胶质细胞激活和脑促炎细胞因子表达增加

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 DOI: 10.1016/j.bbih.2025.101148

Silvia Flaj Prados , Esperanza Herradón Pliego , Carlos Goicoechea Garcia , Eva Ma Sánchez-Robles , Lars Arendt-Nielsen , Cesar Fernández-de-las-Peñas , Visitación López-Miranda

Introduction

Many COVID-19 survivors suffer long-term multi-organ damage leading to some symptoms such as brain fog. Around 25 % of patients report persistent memory loss, concentration difficulties, or other cognitive impairments after a SARS-COV-2 infection. Animal models are crucial for studying the pathophysiology of post-acute COVID-19 sequelae (PASC).

Objective

To assess the presence of neuro-inflammatory and glial activation biomarkers in brain tissue after a SARS-CoV-2 infection in an animal model to better understand the pathophysiology of neurocognitive symptoms.

Methods

Twelve C57BL/6 female hACE2 mice infected with SARS-CoV-2 Omicron variant (BA.1.17 lineage) and eleven non-infected female mice were included. Different proteins evaluating the innate immune activation in neuro-inflammation (TLR4, MyD88, NF-κB signalling pathway), inflammatory state (interleukins IL-6, IL-18 and IL-1β), and glial neuro-inflammatory response (CD11d, Iba1, GFAP expression) were evaluated from cerebral tissue 28 days after infection.

Results

As compared to non-infected mice, significant higher (p = 0.014) post-COVID expression of IL-18 (suggesting an inflammatory state) and significant higher (p = 0.0473) post-COVID GFAP expression (indicating enhanced astrocytic glia activation in response to the infection) was observed in brain tissue. No significant differences in TLR4 (p = 0.512), MyD88 (p = 0.151), NF-κB p65 (p = 0.712), IL-6 (p = 0.962), IL-1β (p = 0.343), CD11d (p = 0.750), and Iba1 (p = 0.935) expressions were observed.

Conclusions

This study provides evidence on brain neuro-inflammation, highlighting glial activation and IL-18 overexpression after an acute SARS-CoV-2 infection. These findings improve current understanding of post-COVID neuroinflammation and could aid in the design of treatment strategies for persistent neurological sequelae, such as cognitive impairment and mental confusion.

许多COVID-19幸存者长期遭受多器官损伤，导致脑雾等症状。大约25%的患者在感染SARS-COV-2后报告持续记忆丧失、注意力集中困难或其他认知障碍。动物模型对于研究COVID-19急性后后遗症（PASC）的病理生理至关重要。目的评估SARS-CoV-2感染动物模型后脑组织中神经炎症和神经胶质活化生物标志物的存在，以更好地了解神经认知症状的病理生理学。方法选取12只感染SARS-CoV-2组克隆变异（BA.1.17）的C57BL/6雌性hACE2小鼠和11只未感染的雌性小鼠。在感染后28天的脑组织中评估神经炎症中评估先天免疫激活的不同蛋白（TLR4, MyD88， NF-κB信号通路），炎症状态（白细胞介素IL-6， IL-18和IL-1β）和胶质神经炎症反应（CD11d, Iba1， GFAP表达）。结果与未感染小鼠相比，感染后脑组织IL-18表达显著升高（p = 0.014）， GFAP表达显著升高（p = 0.0473），提示感染后星形胶质细胞活化增强。TLR4 （p = 0.512）、MyD88 （p = 0.151）、NF-κB p65 （p = 0.712）、IL-6 （p = 0.962）、IL-1β (p = 0.343)、CD11d （p = 0.750）、Iba1 （p = 0.935）的表达差异无统计学意义。结论本研究提供了急性SARS-CoV-2感染后脑神经炎症的证据，突出了胶质细胞激活和IL-18的过表达。这些发现提高了目前对covid后神经炎症的理解，并有助于设计持续性神经系统后遗症（如认知障碍和精神混乱）的治疗策略。

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引用次数: 0

Moderating effects of individual factors on the relationship between inflammation and psychophysiological states in healthy adults 个体因素对健康成人炎症与心理生理状态关系的调节作用

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-11-07 DOI: 10.1016/j.bbih.2025.101135

Kao Yamaoka , Yuri Ishii , Yuri Terasawa

Systemic inflammation affects psychological processes. Although the association between inflammation and psychophysiological state has been extensively investigated in patients with depression or inflammatory disease, how this relationship manifests in healthy individuals is not clearly known. Not all individuals exhibit distress in response to elevated inflammatory markers, suggesting the presence of psychological moderators. Elucidating the effect of elevated inflammatory markers on healthy adults would broaden the understanding of the relationship between inflammation and psychophysiological state. We investigated the moderating effect of individual factors, including emotion regulation, sleep quality, and interoceptive awareness, on the relationship between inflammatory markers and psychophysiological states in healthy adults. A total of 155 participants aged 30–59 years were assessed for inflammatory markers, individual factors, and subjective psychological and physical symptoms. Hierarchical regression and interaction models revealed that individuals with poor emotion regulation or low-quality sleep showed stronger associations between inflammatory markers and symptoms such as fatigue, somatic complaints, depression, and anxiety. Conversely, individuals with effective emotion regulation or high-quality sleep exhibited attenuated or even reversed associations, suggesting protective effects. Interoceptive awareness showed weaker and more context-dependent moderating effects. These results highlight the importance of psychological traits in modulating the effects of inflammation on mental and physical well-being in clinically healthy adults. Targeted interventions for enhancing emotion regulation and sleep quality may mitigate the psycho-physiological burden of inflammation and reduce the risk of future disease onset. The findings underscore the need for individualized psychoneuroimmunological models that incorporate trait-level moderators to explain variability in stress-related health outcomes.

全身性炎症影响心理过程。尽管炎症与心理生理状态之间的关系已经在抑郁症或炎症性疾病患者中得到了广泛的研究，但这种关系如何在健康个体中表现出来尚不清楚。并非所有个体对炎症标志物升高的反应都表现出痛苦，这表明存在心理调节因子。阐明炎症标志物升高对健康成人的影响将拓宽对炎症与心理生理状态之间关系的理解。我们研究了个体因素的调节作用，包括情绪调节、睡眠质量和内感受性意识，在健康成人炎症标志物和心理生理状态之间的关系。共对155名年龄在30-59岁之间的参与者进行了炎症标志物、个体因素以及主观心理和身体症状的评估。层次回归和相互作用模型显示，情绪调节能力差或睡眠质量差的个体在炎症标志物与疲劳、躯体不适、抑郁和焦虑等症状之间表现出更强的关联。相反，具有有效情绪调节或高质量睡眠的个体表现出减弱甚至逆转的关联，表明保护作用。内感受意识表现出较弱的情境依赖性调节效应。这些结果强调了心理特征在调节炎症对临床健康成人心理和身体健康的影响中的重要性。加强情绪调节和睡眠质量的针对性干预可能减轻炎症的心理生理负担，降低未来发病的风险。研究结果强调了个性化心理神经免疫学模型的必要性，该模型包含特质水平的调节因子，以解释压力相关健康结果的可变性。

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引用次数: 0