Brain, behavior, & immunity - health最新文献_第7页

Psychological distress in older adults: associations with epigenetic markers of ageing, inflammation, and depression, and joint effects on mortality 老年人的心理困扰：与衰老、炎症和抑郁的表观遗传标记的关联，以及对死亡率的共同影响

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-12 DOI: 10.1016/j.bbih.2025.101090

Danmeng Lily Li , Xiaojing Xu , Allison M. Hodge , Melissa C. Southey , Graham G. Giles , Roger L. Milne , Pierre-Antoine Dugué

Background

Psychological distress is associated with adverse health outcomes. We aimed to assess whether the health impacts of psychological distress could be captured by epigenetic markers of ageing, inflammation, and depression, and whether these markers and psychological distress have a synergistic association with mortality in older Australians.

Methods

Blood DNA methylation data for 1146 participants (31 % females, mean age: 69 years) in the Melbourne Collaborative Cohort Study were used to calculate epigenetic markers of ageing (PCPhenoAge, PCGrimAge, bAge, DunedinPACE) and inflammation (C-reactive protein [mCRP]), and two methylation scores for depression. Psychological distress was assessed by the Kessler scale (K10). Linear regression was used to assess the associations of K10 with epigenetic markers. Cox models were used to assess the multiplicative and additive interactions of K10 and epigenetic markers in their association with all-cause mortality.

Results

We observed positive associations of K10 with epigenetic markers of ageing and inflammation: per standard deviation (SD), 0.05 (95 %CI: 0.00–0.11) for DunedinPACE to 0.10 (95 %CI: 0.05–0.16) for PCPhenoAge. Associations of epigenetic markers of ageing with mortality were stronger in participants with higher psychological distress. The relative excess risk due to interaction for DunedinPACE was 0.82, 95 %CI: 0.14–1.50.

Conclusion

In older Australians, higher psychological distress was associated with older epigenetic age and higher mCRP. Participants with higher levels of both psychological distress and epigenetic markers of ageing and mCRP had higher mortality risk. These findings highlight links between psychological and biological health, and the potential importance of considering both for disease risk stratification.

心理困扰与不良健康结果相关。我们的目的是评估心理困扰对健康的影响是否可以通过衰老、炎症和抑郁的表观遗传标记来捕捉，以及这些标记和心理困扰是否与澳大利亚老年人的死亡率有协同关联。方法使用墨尔本合作队列研究中1146名参与者（31%为女性，平均年龄：69岁）的血液DNA甲基化数据，计算衰老（PCPhenoAge, PCGrimAge, bAge, DunedinPACE）和炎症（c -反应蛋白[mCRP]）的表观遗传标记，以及抑郁症的两个甲基化评分。采用Kessler量表（K10）评估心理困扰。采用线性回归方法评估K10与表观遗传标记的相关性。Cox模型用于评估K10和表观遗传标记与全因死亡率之间的乘法和加性相互作用。结果我们观察到K10与衰老和炎症的表观遗传标记呈正相关：每标准差（SD）， DunedinPACE为0.05 (95% CI: 0.00-0.11)， PCPhenoAge为0.10 （95% CI: 0.05 - 0.16）。在心理困扰程度较高的参与者中，衰老的表观遗传标记与死亡率的关联更强。DunedinPACE相互作用的相对超额风险为0.82,95% CI: 0.14-1.50。结论在澳大利亚老年人中，较高的心理困扰与较年长的表观遗传年龄和较高的mCRP有关。心理困扰、衰老表观遗传标记和mCRP水平较高的参与者有更高的死亡风险。这些发现强调了心理健康和生物健康之间的联系，以及在疾病风险分层中考虑这两者的潜在重要性。

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引用次数: 0

Biomarker-based profiling of fatigue in childhood cancer survivors: evidence for distinct inflammatory and glial-associated profiles 基于生物标志物的儿童癌症幸存者疲劳谱：不同炎症和神经胶质相关谱的证据

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-11 DOI: 10.1016/j.bbih.2025.101089

Deveny Vanrusselt , Sabine Verschueren , Lize Van Meerbeeck , Jurgen Lemiere , Stephanie Humblet-Baron , Charlotte Sleurs , Anne Uyttebroeck

Background

Fatigue is a prevalent and burdensome late effect in childhood cancer survivors (CCS), yet its biological underpinnings remain poorly understood. This study examined associations between fatigue and blood-based biomarkers in CCS compared to healthy controls (HCs) and explored whether biologically distinct CCS profiles with respect to fatigue could be identified.

Procedure

Eighty CCS (aged 14–28) and 35 age- and sex-matched HCs provided blood samples and completed the Pediatric Quality of Life Inventory Multidimensional Fatigue Scale (PedsQL-MFS). Plasma concentrations of 12 biomarkers (e.g., IL-2, TNF-α, BDNF, Total Tau, NfL, MCP-1, GFAP) were quantified using Meso Scale Discovery immunoassays. Analyses included group comparisons, Spearman correlations, and unsupervised clustering (hierarchical and k-means).

Results

CCS reported significantly higher fatigue than HCs and showed significantly elevated levels of GFAP (d = 0.43), MCP-1 (d = 0.74), and Total Tau (d = 0.54). No individual biomarkers differentiated fatigued from non-fatigued CCS. Clustering revealed two biomarker-based CCS subgroups: one with high levels of inflammatory and neurodegenerative markers, and one with lower levels, yet fatigue severity was comparable. Within-cluster analyses showed distinct patterns: in the low-biomarker group, fatigue was associated with GFAP (ρ = −0.26 and ρ = −0.27, p < 0.05), whereas in the high-biomarker group, fatigue was more consistently linked to IL-8, IL-1α, and TNF-α (ρ = −0.38 to −0.49, p < 0.05).

Conclusion

Findings suggest that fatigue in CCS may be associated with distinct biological pathways, including astrocyte-linked processes in one subgroup and systemic inflammation in another. This suggests the need for more personalized, biomarker-informed strategies to understand and manage fatigue in pediatric cancer survivorship.

疲劳是儿童癌症幸存者（CCS）中一种普遍且繁重的晚期效应，但其生物学基础仍知之甚少。与健康对照（hc）相比，本研究检查了CCS中疲劳和血液生物标志物之间的关系，并探讨了是否可以识别出与疲劳相关的CCS生物学特征。80名CCS（14-28岁）和35名年龄和性别匹配的hc提供了血液样本，并完成了儿童生活质量量表多维疲劳量表（PedsQL-MFS）。使用Meso Scale Discovery免疫测定法定量12种生物标志物（如IL-2、TNF-α、BDNF、Total Tau、NfL、MCP-1、GFAP）的血浆浓度。分析包括分组比较、Spearman相关性和无监督聚类（分层和k-means）。结果sccs报告的疲劳程度明显高于hc， GFAP （d = 0.43）、MCP-1 （d = 0.74）和Total Tau （d = 0.54）水平均显著升高。没有单独的生物标志物区分疲劳和非疲劳CCS。聚类揭示了两个基于生物标志物的CCS亚组：一个具有高水平的炎症和神经退行性标志物，另一个具有较低水平，但疲劳严重程度具有可比性。聚类分析显示出不同的模式：在低生物标志物组中，疲劳与GFAP相关(ρ = - 0.26和ρ = - 0.27, p <；0.05)，而在高生物标志物组中，疲劳与IL-8、IL-1α和TNF-α的关系更为一致(ρ = - 0.38至- 0.49,p <；0.05)。研究结果表明，CCS中的疲劳可能与不同的生物学途径有关，包括星形胶质细胞相关过程和全身炎症。这表明需要更个性化的、生物标志物知情的策略来理解和管理儿童癌症幸存者的疲劳。

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引用次数: 0

Acute systemic endotoxin administration elevates neuroimmune markers and sickness behaviors in male and female Peromyscus californicus 急性全身性内毒素给药可提高男性和女性加利福尼亚细肌虫的神经免疫标记物和疾病行为

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-10 DOI: 10.1016/j.bbih.2025.101087

Amy J. Wegener , Hannah Stadtler , Hannah D. Fulenwider , Erica R. Glasper , Gretchen N. Neigh

The California mouse is a biparental monogamous rodent species used to study the neuroendocrine mechanisms underlying social stressors, but there is limited research investigating the neuroimmune response within the species to facilitate our understanding of stress and neuroinflammation interactions. The data herein provide an assessment of behavior, somatic metrics, and gene expression changes within the prefrontal cortex (PFC) and hippocampus (HPC) at 4- and 24-h following a single peripheral injection of the endotoxin lipopolysaccharide (LPS) in males and females. We observed effects of LPS on spleen weights and both males and females demonstrated sickness-like behaviors at 24 h as indicated by assessment of nest building quality. Within both sexes in both the PFC and HPC, proinflammatory genes (i.e., tumor necrosis factor (TNF) and interleukin-1β (IL-1β)) were increased at 4 h following LPS, with a return towards expression levels of saline controls by 24 h. Gene expression of GFAP, Cd68, and Complement C3 were elevated by LPS in both sexes and both brain regions with highest expression observed at 24 h. Given that mitochondria function is impacted by inflammatory mediators, we isolated functional synaptic mitochondria to assess for changes in oxygen consumption. Mitochondria spare capacity was elevated in the PFC 4 h after LPS, but only in males. LPS did not alter mitochondrial function at any time point within the HPC for either sex. Collectively, these data demonstrate that both male and female California mice exhibit peripheral and neuroinflammatory consequences of an acute LPS challenge with relative sparing of synaptic mitochondrial function. These data provide a framework for building California mouse studies focused on the intersection of social stress and inflammation on behavioral outcomes.

加利福尼亚鼠是一种双亲一夫一妻制的啮齿类动物，用于研究社会压力源的神经内分泌机制，但对物种内神经免疫反应的研究有限，以促进我们对压力和神经炎症相互作用的理解。本文的数据提供了在单次外周注射内毒素脂多糖（LPS）后4和24小时，男性和女性前额叶皮质（PFC）和海马（HPC）内行为、体细胞指标和基因表达变化的评估。我们观察了LPS对脾脏重量的影响，雄鼠和雌鼠在24 h时都表现出类似疾病的行为，这是通过对筑巢质量的评估得出的。在PFC和HPC的两性中，促炎基因（即肿瘤坏死因子（TNF）和白细胞介素-1β (IL-1β)）在LPS后4小时增加，24小时后恢复到生理盐水对照组的表达水平。GFAP、Cd68和补体C3的基因表达在两性和两个脑区均升高，24小时时表达最高。我们分离功能性突触线粒体来评估氧消耗的变化。LPS后4小时PFC线粒体备用容量升高，但仅在雄性中。LPS在HPC内的任何时间点均未改变线粒体功能。总的来说，这些数据表明雄性和雌性加利福尼亚小鼠都表现出急性LPS刺激的外周和神经炎症后果，突触线粒体功能相对保留。这些数据为建立加利福尼亚小鼠研究提供了一个框架，该研究的重点是社会压力和炎症对行为结果的影响。

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引用次数: 0

Anxiety and nonpsychotic mental disorders in acute urticaria 急性荨麻疹的焦虑和非精神病性精神障碍

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-10 DOI: 10.1016/j.bbih.2025.101088

Eli Magen , Eugene Merzon , Shai Ashkenazi , Abraham Weizman , Iris Manor , Israel Magen , Avi Yakov , Akim Geishin , Ilan Green , Avivit Golan-Cohen , Shlomo Vinker , Ariel Israel

Background

Acute urticaria (AU) is characterized by the sudden onset of wheals, angioedema, or both, with symptoms resolving within 6 weeks. While the association between chronic urticaria and mental health disorders is well-documented, the relationship between AU and psychological conditions remains understudied.

Objective

To investigate the association between AU and anxiety and personality disorders, and to explore the potential psychoneuroimmunological mechanisms underlying these relationships.

Methods

We conducted a population-based case-control study using the comprehensive electronic health records database of Leumit Health Services in Israel. The study included 72,805 AU patients and 291,220 matched controls. Subjects were matched for gender, age, ethnicity, year of first documented visit, and socioeconomic status. We analyzed the 20-year prevalence of anxiety disorders, personality disorders, and various nonpsychotic mental disorders in both groups.

Results

AU patients demonstrated significantly higher prevalence of anxiety disorders (7.02 % vs. 5.22 %, p < 0.001, OR = 1.37 [95 % CI: 1.33–1.42]), personality disorders (0.23 % vs. 0.134 %, p < 0.001, OR = 1.73 [95 % CI: 1.44–2.08]), and adjustment disorders (0.91 % vs. 0.67 %, p < 0.001, OR = 1.37 [95 % CI: 1.25–1.50]) compared to controls. Particularly notable were the associations with personality disorders characterized by persistent mood disturbances (OR = 1.91 [95 % CI: 1.53–2.38]) and adjustment disorders with depressive features (OR = 1.49 [95 % CI: 1.27–1.74]).

Conclusions

Our findings reveal significant associations between AU and various mental health disorders, particularly anxiety and personality disorders. These associations suggest a complex bidirectional relationship mediated through psychoneuroimmunological pathways involving the HPA axis, mast cell activation, and inflammatory cytokines. We recommend implementing specific screening tools (HADS, GAD-7) and a stepped-care approach for integrated dermatological and psychological management of AU patients.

背景：急性荨麻疹（AU）的特点是突然发作皮疹、血管性水肿或两者兼而有之，症状在6周内消退。虽然慢性荨麻疹和精神健康障碍之间的关系有充分的文献记载，但AU和心理状况之间的关系仍未得到充分的研究。目的探讨AU与焦虑、人格障碍的关系，并探讨其潜在的心理神经免疫学机制。方法利用以色列Leumit卫生服务中心的综合电子健康记录数据库，开展了一项基于人群的病例对照研究。该研究包括72,805名AU患者和291,220名匹配的对照组。受试者根据性别、年龄、种族、首次就诊年份和社会经济地位进行匹配。我们分析了20年来两组患者中焦虑症、人格障碍和各种非精神病性精神障碍的患病率。结果与对照组相比，sau患者的焦虑症患病率（7.02%比5.22%,p < 0.001, OR = 1.37 [95% CI: 1.33-1.42]）、人格障碍患病率（0.23%比0.134 %,p < 0.001, OR = 1.73 [95% CI: 1.44-2.08]）和适应性障碍患病率（0.91%比0.67%,p < 0.001, OR = 1.37 [95% CI: 1.25-1.50]）显著高于对照组。特别值得注意的是与持续情绪障碍为特征的人格障碍（OR = 1.91 [95% CI: 1.53-2.38]）和抑郁特征的适应障碍（OR = 1.49 [95% CI: 1.27-1.74]）的关联。结论AU与多种精神健康障碍，特别是焦虑和人格障碍之间存在显著关联。这些关联提示了一种复杂的双向关系，通过心理神经免疫途径介导，包括HPA轴、肥大细胞激活和炎症细胞因子。我们建议实施特定的筛查工具（HADS, GAD-7）和分步护理方法，对AU患者进行皮肤病学和心理综合管理。

{"title":"Anxiety and nonpsychotic mental disorders in acute urticaria","authors":"Eli Magen , Eugene Merzon , Shai Ashkenazi , Abraham Weizman , Iris Manor , Israel Magen , Avi Yakov , Akim Geishin , Ilan Green , Avivit Golan-Cohen , Shlomo Vinker , Ariel Israel","doi":"10.1016/j.bbih.2025.101088","DOIUrl":"10.1016/j.bbih.2025.101088","url":null,"abstract":"<div><h3>Background</h3><div>Acute urticaria (AU) is characterized by the sudden onset of wheals, angioedema, or both, with symptoms resolving within 6 weeks. While the association between chronic urticaria and mental health disorders is well-documented, the relationship between AU and psychological conditions remains understudied.</div></div><div><h3>Objective</h3><div>To investigate the association between AU and anxiety and personality disorders, and to explore the potential psychoneuroimmunological mechanisms underlying these relationships.</div></div><div><h3>Methods</h3><div>We conducted a population-based case-control study using the comprehensive electronic health records database of Leumit Health Services in Israel. The study included 72,805 AU patients and 291,220 matched controls. Subjects were matched for gender, age, ethnicity, year of first documented visit, and socioeconomic status. We analyzed the 20-year prevalence of anxiety disorders, personality disorders, and various nonpsychotic mental disorders in both groups.</div></div><div><h3>Results</h3><div>AU patients demonstrated significantly higher prevalence of anxiety disorders (7.02 % vs. 5.22 %, <em>p < 0.001</em>, OR = 1.37 [95 % CI: 1.33–1.42]), personality disorders (0.23 % vs. 0.134 %, <em>p < 0.001</em>, OR = 1.73 [95 % CI: 1.44–2.08]), and adjustment disorders (0.91 % vs. 0.67 %, <em>p < 0.001</em>, OR = 1.37 [95 % CI: 1.25–1.50]) compared to controls. Particularly notable were the associations with personality disorders characterized by persistent mood disturbances (OR = 1.91 [95 % CI: 1.53–2.38]) and adjustment disorders with depressive features (OR = 1.49 [95 % CI: 1.27–1.74]).</div></div><div><h3>Conclusions</h3><div>Our findings reveal significant associations between AU and various mental health disorders, particularly anxiety and personality disorders. These associations suggest a complex bidirectional relationship mediated through psychoneuroimmunological pathways involving the HPA axis, mast cell activation, and inflammatory cytokines. We recommend implementing specific screening tools (HADS, GAD-7) and a stepped-care approach for integrated dermatological and psychological management of AU patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101088"},"PeriodicalIF":3.5,"publicationDate":"2025-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144864355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Altered gut microbial diversity, composition, and metabolomic potential in patients with major depressive disorder and recent suicide attempt 重度抑郁症和近期自杀未遂患者肠道微生物多样性、组成和代谢组学潜力的改变

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-05 DOI: 10.1016/j.bbih.2025.101081

Emese Prandovszky , Hua Liu , Emily G. Severance , Victor W. Splan , Faith B. Dickerson , Robert H. Yolken

This study investigates the role of the gut microbiome in suicidal behavior among individuals with major depressive disorder (MDD). Fecal samples from 50 hospitalized patients with MDD, including 35 with recent suicide attempts (60 % female) and 15 without a history of suicide (73 % female), were analyzed using 16S rRNA and shotgun sequencing to assess microbiome diversity and metabolic potential. Results revealed that suicide attempters exhibited significantly greater microbial richness and distinct beta-diversity patterns. Notably, they had higher levels of Fenollaria timonensis and lower levels of Corynebacterium aurimucosum. Additionally, 25 metabolic pathways differed between groups, with several linked to energy metabolism and amino acid processing—processes previously associated with MDD and suicidal behavior. These findings suggest that microbiome composition may influence suicide risk through gut-brain axis-mediated pathways, although due to the exploratory nature of this study further investigation is needed to validate our findings. Given the microbiome's modifiability, future research should explore microbial-targeted interventions as a potential strategy for suicide prevention in individuals with MDD.

本研究探讨了肠道微生物组在重度抑郁症（MDD）患者自杀行为中的作用。采用16S rRNA和霰弹枪测序对50例重度抑郁症住院患者的粪便样本进行分析，其中包括35例近期自杀未遂（60%为女性）和15例无自杀史（73%为女性），以评估微生物组多样性和代谢潜力。结果显示，自杀未遂者表现出明显更高的微生物丰富度和不同的β多样性模式。值得注意的是，他们有较高水平的铁薄荷虫和较低水平的金棒状杆菌。此外，25种代谢途径在两组之间有所不同，其中一些与能量代谢和氨基酸加工有关，这些过程先前与重度抑郁症和自杀行为有关。这些发现表明，微生物组组成可能通过肠-脑轴介导的途径影响自杀风险，尽管由于本研究的探索性，需要进一步的调查来验证我们的发现。鉴于微生物组的可修饰性，未来的研究应该探索以微生物为目标的干预措施作为预防重度抑郁症患者自杀的潜在策略。

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引用次数: 0

Brain nitric oxide and inflammation in chronic intermittent hypoxia: Contributors to cognitive impairment and hypertension 慢性间歇性缺氧中的脑一氧化氮和炎症：导致认知障碍和高血压

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-08-04 DOI: 10.1016/j.bbih.2025.101077

Cephas B. Appiah, Ato O. Aikins, George E. Farmer, J. Thomas Cunningham

Chronic intermittent hypoxia (CIH) is a key feature of obstructive sleep apnea (OSA) and leads to physiological changes that can cause cardiovascular and neurological issues. This review explores the role of nitric oxide (NO) and inflammation in the development of CIH-induced health problems, specifically focusing on hypertension and cognitive dysfunction. We synthesize current evidence regarding how CIH modulates inflammatory processes and NO signaling in different brain regions, especially autonomic control centers crucial for cardiovascular regulation. We also discuss the activation of proinflammatory transcription factors, the generation of reactive oxygen species, and the involvement of pattern recognition receptors in CIH-induced neuroinflammation. Regarding cardiovascular changes associated with CIH, we focus on the effects of NO and inflammation in central autonomic regions such as the organum vasculosum of the lamina terminalis (OVLT), subfornical organ (SFO), median preoptic nucleus (MnPO), and paraventricular nucleus (PVN), shedding light on their contributions to sustained hypertension in CIH. The review delves into the latest findings on sex differences in CIH-induced neuroinflammation. In examining the current knowledge, we have pinpointed significant gaps in understanding, especially concerning the specific mechanisms of NO and inflammation interactions in different brain regions during CIH. This review provides insights into potential therapeutic targets and emphasizes the need for further research to develop more effective treatments for OSA-related cardiovascular and neurological complications.

慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停（OSA）的一个重要特征，并导致可引起心血管和神经问题的生理变化。这篇综述探讨了一氧化氮（NO）和炎症在cih诱导的健康问题发展中的作用，特别是高血压和认知功能障碍。我们综合了目前关于CIH如何调节不同脑区炎症过程和NO信号的证据，特别是对心血管调节至关重要的自主控制中心。我们还讨论了促炎转录因子的激活，活性氧的产生，以及模式识别受体在cih诱导的神经炎症中的参与。关于与CIH相关的心血管变化，我们关注一氧化氮和炎症在中枢自主神经区域的影响，如终末板血管器官（OVLT）、皮质下器官（SFO）、正中视前核（MnPO）和室旁核（PVN），揭示它们在CIH中持续高血压的作用。这篇综述深入研究了cih诱导的神经炎症的性别差异的最新发现。在检查现有知识时，我们已经确定了理解上的重大差距，特别是关于CIH期间不同脑区NO和炎症相互作用的具体机制。这篇综述提供了潜在的治疗靶点，并强调需要进一步研究开发更有效的治疗osa相关心血管和神经系统并发症的方法。

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引用次数: 0

Progranulin modulates inflammatory responses to immune challenges by suppressing circulating cytokine levels 前颗粒蛋白通过抑制循环细胞因子水平调节对免疫挑战的炎症反应

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-07-31 DOI: 10.1016/j.bbih.2025.101084

Takashi Matsuwaki, Keitaro Yamanouchi, Masugi Nishihara

Progranulin (PGRN) is a multifunctional growth factor that is widely expressed throughout the body. It has recently been reported that PGRN haploinsufficiency is a major factor causing frontotemporal lobar dementia. Subsequently, many studies, including ours, have demonstrated the neuroprotective and neurotrophic functions of PGRN. We have also shown that PGRN is involved in voluntary exercise-induced neurogenesis and the suppression of neuroinflammation after traumatic brain injury. Because PGRN is expressed in immune cells in peripheral and central tissues, the main purpose of the present study was to elucidate the role of PGRN in inflammatory responses to immune challenges. Male C57BL/6J wild-type (WT) mice or PGRN-deficient (KO) mice of the same background were used in all experiments. We intraperitoneally injected lipopolysaccharide (LPS, 120 μg/kg) into the animals and measured their body temperature for 9 h during the day and their food intake for 24 h. Although LPS induced a fever response and anorexia in mice of both genotypes, the symptoms were much more severe in the KO mice. LPS is known to induce the secretion of inflammatory cytokines, which transmit immune signals from peripheral to central tissues. Thus, we subsequently determined the serum concentrations of the inflammatory cytokines IL-1β, IL-6, and TNF-α at 0, 1, and 3 h after LPS injection. KO mice showed a significantly stronger induction of IL-6 at 3 h and TNF-α at both 1 and 3 h after injection. IL-1β also tended to have stronger induction at 3 h in KO mice, although the difference was not statistically significant. In WT mice, LPS injection increased PGRN mRNA expression but did not enhance serum PGRN concentration. These results suggest that PGRN suppresses excessive inflammatory responses by moderating the secretion of inflammatory cytokines by functioning inside immune cells.

前颗粒蛋白（PGRN）是一种广泛表达于全身的多功能生长因子。最近有报道称，PGRN单倍体功能不全是导致额颞叶痴呆的主要因素。随后，包括我们在内的许多研究都证明了PGRN的神经保护和神经营养功能。我们还发现PGRN参与了外伤性脑损伤后自发性运动诱导的神经发生和神经炎症的抑制。由于PGRN在外周和中枢组织的免疫细胞中表达，因此本研究的主要目的是阐明PGRN在免疫挑战的炎症反应中的作用。所有实验均采用相同背景的雄性C57BL/6J野生型（WT）小鼠或pgrn缺陷（KO）小鼠。我们通过腹腔注射脂多糖（LPS, 120 μg/kg），测量小鼠白天9 h的体温和24 h的摄食量。尽管LPS在两种基因型小鼠中都引起了发热反应和厌食，但KO小鼠的症状要严重得多。已知LPS诱导炎性细胞因子的分泌，将免疫信号从外周组织传递到中枢组织。因此，我们随后测定了LPS注射后0、1和3小时血清中炎症因子IL-1β、IL-6和TNF-α的浓度。KO小鼠注射后3 h IL-6和1、3 h TNF-α的诱导作用明显增强。IL-1β在KO小鼠中也倾向于在3 h时具有更强的诱导作用，尽管差异无统计学意义。在WT小鼠中，LPS注射增加了PGRN mRNA的表达，但没有增加血清PGRN浓度。这些结果表明，PGRN通过在免疫细胞内发挥作用，通过调节炎症细胞因子的分泌来抑制过度炎症反应。

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引用次数: 0

Detection of autoantibodies against Interferon Type I in patients with autochthonous West Nile Virus encephalitis 西尼罗病毒脑炎患者ⅰ型干扰素自身抗体的检测

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-07-30 DOI: 10.1016/j.bbih.2025.101085

Jan Braune , Lorenz Pechstein , Christian Meisel , Tim Meyer , Julia Melchert , Victor Max Corman , Christiana Franke , Thomas Schneider

West Nile virus (WNV) is a neurotropic flavivirus that has become a global concern because of its rapid geographical spread and its capacity to cause severe disease in humans. Although often asymptomatic, infection can lead to life-threatening neuroinvasive disease (WNND) in a small percentage of cases, particularly among elderly individuals and individuals with compromised immune responses. We present three cases of autochthonous WNND from Germany from 2023 to 2024, which showcase various neurological manifestations and their correlation with immune responses. Two elderly men developed severe encephalitis symptoms, whereas one patient presented with only mild encephalitis symptoms but severe flaccid paresis. Notably, two patients (Patients One and Two) had neutralizing autoantibodies against interferon-α2 and interferon-ω, along with neutralizing antibodies against interferon-β in Patient One. This may implicate impaired viral immunity and severe disease progression. Complete genome sequencing revealed lineage 2 sequences with high similarity to WNV sequences obtained from other patients, birds, and mosquitoes in Germany. Our report raises concerns about the underdiagnosis of WNV in Germany, where human cases remain underreported despite the presence of endemic infections in animals and competent mosquito vectors. Given the increasing prevalence of WNV in Europe, intensified surveillance and awareness are critical. The variability in clinical presentations and the potential for fatal outcomes underscore the importance of early recognition and individualized management strategies.

西尼罗病毒（WNV）是一种嗜神经黄病毒，由于其迅速的地理传播和在人类中引起严重疾病的能力而成为全球关注的问题。尽管通常无症状，但在少数病例中，感染可导致危及生命的神经侵袭性疾病（WNND），特别是在老年人和免疫反应受损的个体中。我们报告了2023年至2024年来自德国的三例本地WNND，表现出各种神经学表现及其与免疫反应的相关性。两名老年男子出现严重的脑炎症状，而一名患者仅出现轻度脑炎症状，但出现严重的弛缓性麻痹。值得注意的是，两名患者（患者1和患者2）具有针对干扰素-α2和干扰素-ω的中和抗体，以及患者1中针对干扰素-β的中和抗体。这可能涉及病毒免疫功能受损和严重的疾病进展。全基因组测序显示，谱系2序列与从德国其他患者、鸟类和蚊子中获得的西尼罗河病毒序列高度相似。我们的报告引起了对德国西尼罗河病毒诊断不足的关注，尽管在动物和有能力的蚊子媒介中存在地方性感染，但德国的人间病例仍然报告不足。鉴于西尼罗河病毒在欧洲日益流行，加强监测和提高认识至关重要。临床表现的可变性和潜在的致命结果强调了早期识别和个性化管理策略的重要性。

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引用次数: 0

Outness predicts greater leukocyte telomere length in sexually minoritized men with HIV who use methamphetamine Outness预测使用甲基苯丙胺的性少数艾滋病毒感染者白细胞端粒长度更大

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-07-30 DOI: 10.1016/j.bbih.2025.101086

Renessa S. Williams , Ariana Johnson , Michael Miller-Perusse , Annesa Flentje , Judy Moskowitz , Samantha E. Dilworth , Keith J. Horvath , Adam W. Carrico , Brad E. Aouizerat , Delaram Ghanooni

Objective

This longitudinal study aimed to examine the associations of sexual minority stress and outness with leukocyte telomere length across time among sexually minority men (SMM) with HIV who use methamphetamine.

Methods

A sample of 91 SMM with HIV with biologically confirmed recent methamphetamine use completed measures of sexual minority stress and outness at the baseline visit in a randomized controlled trial. Telomere length was measured over 15 months using extracted leukocyte DNA Statistical analyses were performed using bivariate analyses and generalized estimation equations to examine the independent association between baseline outness and leukocyte telomere length, adjusting for chronological age and recent stimulant use.

Results

Greater outness was significantly associated with longer telomere length (estimate = 0.008; CI: 0.001–0.008) after adjusting for chronological age and stimulant use. There was no evidence that stimulant use, intervention assignment, or race/ethnicity moderated the association between outness and greater leukocyte-telomere length. Sexual minority stress was not significantly associated with leukocyte-telomere length.

Conclusion

Findings are among the first to demonstrate that greater outness is associated with slower biological aging in SMM. Further research is needed to elucidate the bio-behavioral mechanisms linking outness and greater leukocyte-telomere length.

目的：本纵向研究旨在探讨性少数男性（SMM）使用甲基苯丙胺的HIV感染者的性少数压力和外出与白细胞端粒长度的关系。方法在一项随机对照试验中，91例生物学上证实近期使用甲基苯丙胺的HIV感染者在基线就诊时完成了性少数派压力和外出的测量。使用提取的白细胞DNA在15个月内测量端粒长度，使用双变量分析和广义估计方程进行统计分析，以检查基线外出度和白细胞端粒长度之间的独立关联，调整了实际年龄和最近使用的兴奋剂。结果外径越大，端粒长度越长(估计= 0.008；CI: 0.001-0.008)，在调整了实际年龄和兴奋剂使用后。没有证据表明兴奋剂的使用、干预措施的分配或种族/民族调节了外向度和更大的白细胞端粒长度之间的关联。性少数应激与白细胞端粒长度无显著相关。结论研究结果是第一个证明较大的户外活动与SMM中较慢的生物衰老相关的研究。进一步的研究需要阐明生物行为机制连接外型和更大的白细胞端粒长度。

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引用次数: 0

MicroRNA-124–3p regulates NPY to affect appetite in individuals with depressive disorder MicroRNA-124-3p调节NPY影响抑郁症患者的食欲

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-07-30 DOI: 10.1016/j.bbih.2025.101083

Qianfa Yuan , Chunshui Yu , Jing Lu , Lingxiao Fang , Leiyu Kuang , Zhizhong Xu , Chunyan Wen , WeiChao Su , Yan Qiu , Zhiyuan Huang , Xianhua Zhang , Jue He

While the pathogenesis of depression has been extensively studied, the mechanisms underlying appetite suppression in depression remain poorly understood. This study aimed to elucidate the role of the microRNA-124–3p (miR-124–3p)/neuropeptide Y (NPY) axis in regulating appetite during depression. We examined the relationship between body weight fluctuations and serum miR-124–3p/NPY levels in major depressive disorder (MDD) patients and assessed correlations between NPY levels and appetite scores. Chronic unpredictable mild stress (CUMS) and lipopolysaccharide (LPS)-induced depression mouse models were established to monitor food intake and body weight fluctuations. Hippocampal and cortical tissues were collected to measure miR-124–3p and NPY expression. The miR-124–3p antagomir (inhibitor) and agomir (activator) were subsequently administered to LPS-induced mice to evaluate changes in NPY expression. Clinical studies have confirmed the interactions among miR-124–3p, NPY, and appetite regulation. MDD patients presented elevated serum levels of miR-124–3p, reduced NPY content, and a positive correlation between NPY levels and both appetite scores and body weight. In depression model mice, miR-124–3p expression was increased in the hippocampus and cortex, whereas NPY expression was decreased. Inhibition of miR-124–3p activity enhanced NPY expression, leading to weight gain. Conversely, the activation of miR-124–3p reduces NPY expression, resulting in weight loss. Our study demonstrated that miR-124–3p negatively regulates NPY to mediate appetite suppression in depression. Targeting this axis could provide novel therapeutic strategies for managing weight loss and appetite dysfunction in MDD patients.

虽然抑郁症的发病机制已经被广泛研究，但抑郁症中食欲抑制的机制仍然知之甚少。本研究旨在阐明microRNA-124-3p (miR-124-3p)/神经肽Y （NPY）轴在抑郁症食欲调节中的作用。我们研究了重度抑郁症（MDD）患者体重波动与血清miR-124-3p /NPY水平之间的关系，并评估了NPY水平与食欲评分之间的相关性。建立慢性不可预测轻度应激（CUMS）和脂多糖（LPS）诱导的抑郁小鼠模型，监测食物摄入量和体重波动。收集海马和皮质组织，检测miR-124-3p和NPY的表达。随后将miR-124-3p拮抗剂（抑制剂）和agomir（激活剂）给予lps诱导的小鼠，以评估NPY表达的变化。临床研究证实了miR-124-3p、NPY和食欲调节之间的相互作用。MDD患者血清miR-124-3p水平升高，NPY含量降低，NPY水平与食欲评分和体重呈正相关。在抑郁模型小鼠中，miR-124-3p在海马和皮质中的表达升高，而NPY的表达降低。抑制miR-124-3p活性可增强NPY表达，导致体重增加。相反，miR-124-3p的激活降低了NPY的表达，导致体重减轻。我们的研究表明miR-124-3p负调控NPY介导抑郁症的食欲抑制。以这条轴为靶点，可以为重度抑郁症患者的体重减轻和食欲障碍提供新的治疗策略。

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引用次数: 0