Brain, behavior, & immunity - health最新文献_第6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 Epub Date: 2025-11-14 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

Baicalein alleviates long-term cognitive impairments induced by repeated neonatal sevoflurane exposure via inhibition of cortical microglial TLR4/NF-kB signaling 黄芩素通过抑制皮质小胶质细胞TLR4/NF-kB信号通路，减轻新生儿反复七氟醚暴露引起的长期认知障碍

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 Epub Date: 2025-11-03 DOI: 10.1016/j.bbih.2025.101126

Yingqiao Niu , Qiuting Zeng , Yan Yang , Wenbo Liu , Hui Zhang , Shuyu Chen , Xiaomin Li

Sevoflurane, a widely used pediatric anesthetic, has been associated with long-term cognitive impairments following repeated neonatal exposure. Baicalein, a flavonoid derived from Scutellaria baicalensis, exhibits neuroprotective and anti-inflammatory properties. This study evaluated whether baicalein can mitigate sevoflurane-induced neuroinflammation and cognitive deficits in developing rats. Neonatal rats were exposed to sevoflurane (3 %, 2 h/day) from postnatal day (P) 6 to P8. In the intervention group, baicalein (50 mg/kg) was administered intraperitoneally from P6 to P8 and orally via drinking water from P21 to P35. Cognitive performance was assessed between P35 and P40 using the open field test, novel object recognition, and fear conditioning paradigms. Brain tissues were collected for Western blot, ELISA, and immunofluorescence analyses. Baicalein treatment significantly attenuated sevoflurane-induced deficits in memory and learning, particularly in the novel object recognition and fear conditioning tasks. Mechanistically, baicalein inhibited microglial activation, reduced cortical expression of TLR4 and phosphorylated NF-κB p65, and decreased pro-inflammatory mediators including iNOS, IL-1β, and IL-6 at P8. These findings indicate that repeated neonatal sevoflurane exposure impairs cognitive function via microglial-mediated neuroinflammation, and that baicalein's neuroprotective effect is at least partly attributable to modulation of cortical microglial activity via TLR4/NF-κB signaling. This study highlights baicalein as a promising therapeutic strategy to prevent long-term neurodevelopmental deficits in neonates.

七氟醚是一种广泛使用的儿科麻醉剂，与新生儿反复接触后的长期认知障碍有关。黄芩素是从黄芩中提取的黄酮类化合物，具有神经保护和抗炎作用。本研究评估黄芩素是否能减轻七氟醚诱导的大鼠神经炎症和认知缺陷。从出生后第6天至第8天，新生大鼠暴露于七氟醚（3%，2小时/天）。干预组在P6 ~ P8期间腹腔注射黄芩素50 mg/kg，在P21 ~ P35期间通过饮用水口服黄芩素。在P35和P40之间，使用开放场测试、新物体识别和恐惧条件反射范式评估认知表现。收集脑组织进行Western blot、ELISA和免疫荧光分析。黄芩素治疗显著减轻了七氟醚引起的记忆和学习缺陷，特别是在新物体识别和恐惧条件反射任务中。机制上，黄芩素抑制小胶质细胞活化，降低皮层TLR4和磷酸化NF-κB p65的表达，降低促炎介质包括iNOS、IL-1β和IL-6在P8的表达。这些研究结果表明，新生儿反复接触七氟醚可通过小胶质介导的神经炎症损害认知功能，黄芩素的神经保护作用至少部分可归因于TLR4/NF-κB信号通路对皮质小胶质活性的调节。本研究强调黄芩素是预防新生儿长期神经发育缺陷的一种有前景的治疗策略。

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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 Epub Date: 2025-12-02 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

Plasma profiles of neurology-related proteins in at-risk mental state and first-episode psychosis: Associations with psychotic symptoms and cognitive performance 高危精神状态和首发精神病患者的血浆神经学相关蛋白谱：与精神病症状和认知表现的关系

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.bbih.2025.101134

Martí Llaurador-Coll , Itziar Montalvo , Francesc Estrada , Vanessa Sánchez-Gistau , Henrik Zetterberg , Javier Labad , Andrea L. Benedet , Elisabet Vilella

Background

Early diagnosis of psychosis is crucial, and biomarker detection may provide insights into the pathophysiology of psychosis and the potential for the development of early diagnostic tools. In particular, blood-based proteomic profiling has yielded promising results for psychiatric disorders because of the use of novel high-throughput techniques and the feasibility of performing blood extractions in routine clinical practice.

Study design and methodology

Here, we studied 182 participants (33.3 % females,

\overline{X}

_age = 24.66 ± 5.05), comprising 50 healthy controls (HCs), 37 patients with an at-risk mental state (ARMS) and 95 patients with a first episode of psychosis (FEP). We used a panel of 92 neurology-related proteins in a multiplex immunoassay to identify the plasma protein profiles of each group, their coexpression patterns and biological relevance, and their associations with psychotic symptoms and cognitive performance.

Results

CPA2 was overexpressed in both ARMS participants (β = 0.876, adj. p = 0.009) and FEP participants (β = 0.568, adj. p = 0.011) compared with HCs. In FEP participants, in addition to CPA2, 31 other proteins were overexpressed, with GFRA1 being the most differentially expressed protein (β = 1.159, adj. p < 0.001). Coexpression clusters in FEP patients were involved in several biological processes, such as the regulation of myelination, cell adhesion, multicellular organismal processes and axon guidance. In ARMS patients, THY1 expression was inversely correlated with symptom severity (ρ = −0.640, adj. p = 0.039), and IL12 expression was correlated with cognitive performance (ρ = 0.707, adj. p = 0.007); however, no further correlations were found after the false discovery rate adjustment.

Conclusions

Our findings suggest the involvement of CPA2, GFRA1 and IL12, among other neurology-related proteins, in the early phases of psychosis, which, if confirmed, could become promising biomarkers for diagnosis, psychotic symptom development and psychosis-associated cognitive impairment. However, future studies with larger samples, a longitudinal design, and more extensive proteomic panels are needed to validate these biomarkers and refine their clinical applicability.

背景精神病的诊断是至关重要的，生物标志物检测可以提供对精神病病理生理学的见解和早期诊断工具的发展潜力。特别是，基于血液的蛋白质组学分析在精神疾病方面产生了有希望的结果，因为使用了新的高通量技术和在常规临床实践中进行血液提取的可行性。研究设计和方法在这里，我们研究了182名参与者（33.3%为女性，X - age = 24.66±5.05），其中包括50名健康对照（hc）， 37名有危险精神状态（ARMS）的患者和95名有首发精神病（FEP）的患者。我们在多重免疫分析中使用了一组92种神经学相关蛋白，以确定每组的血浆蛋白谱、它们的共表达模式和生物学相关性，以及它们与精神病症状和认知表现的关联。结果scpa2在ARMS组（β = 0.876, adj. p = 0.009）和FEP组（β = 0.568, adj. p = 0.011）与hc组相比均过表达。在FEP参与者中，除了CPA2外，还有31种其他蛋白过表达，其中GFRA1是差异表达最多的蛋白（β = 1.159, adj. p < 0.001）。FEP患者的共表达簇参与多个生物学过程，如髓鞘形成、细胞粘附、多细胞有机体过程和轴突引导的调节。在ARMS患者中，THY1表达与症状严重程度呈负相关（ρ = - 0.640, adj. p = 0.039）， IL12表达与认知能力相关（ρ = 0.707, adj. p = 0.007）；然而，调整错误发现率后，没有发现进一步的相关性。结论研究结果提示CPA2、GFRA1和IL12等神经相关蛋白参与了精神病的早期阶段，如果得到证实，这些蛋白可能成为诊断、精神病症状发展和精神病相关认知障碍的有希望的生物标志物。然而，未来的研究需要更大的样本，纵向设计和更广泛的蛋白质组学面板来验证这些生物标志物并完善其临床适用性。

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引用次数: 0

Natural-cause mortality and C-reactive protein levels in patients with schizophrenia spectrum disorders: A prospective total cohort study 精神分裂症谱系障碍患者的自然原因死亡率和c反应蛋白水平：一项前瞻性全队列研究

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 Epub Date: 2025-11-04 DOI: 10.1016/j.bbih.2025.101133

F. Fathian , I. Divkovic , M. Fagerbakke Strømme , A. Mykletun , R.A. Kroken , C.A. Bartz-Johannessen , E. Johnsen

Background

Schizophrenia spectrum disorders (SSD) are associated with an excess mortality risk compared with the general population. The involvement of low-grade inflammation and elevated C-reactive protein (CRP) levels is well established in SSD. However, associations between CRP and mortality risk in SSD are less investigated.

Aim

To investigate the association between the baseline CRP level and natural-cause mortality risk in SSD.

Methods

We included all patients with an SSD diagnosis and baseline CRP measurement from an open cohort study of consecutively admitted patients to a psychiatric acute unit at Haukeland University Hospital, Bergen, Norway, between May 1, 2005 and June 15, 2014. All patients were followed until the time of death or censoring/study end, up to 18.6 years, and only the assessments at admission were the focus of the present study. A competing risk model was used, adjusting for age and sex.

Results

Among 1315 individuals, 245 (19 %) died of natural causes; among these patients, 66 (27 %) deaths were related to cardiovascular disease (CVD). Elevated baseline CRP levels of 1.0 ≤ CRP <3.0 mg/L were significantly associated with increased natural-cause mortality risk (adjusted hazard ratio [AHR], 1.88; 95 % confidence interval [CI], 1.22–2.88; p-value, 0.004), with a stronger association for CRP ≥3.0 mg/L (AHR, 2.28; 95 % CI, 1.50–3.48; p-value, <0.001), compared with patients with CRP <1.0 mg/L. Moreover, baseline CRP ≥3.0 mg/L was associated with increased CVD-related mortality risk (AHR, 3.12; 95 % CI, 1.16–8.41; p-value, 0.024).

Conclusions

Elevated CRP levels were associated with increased natural-cause mortality and, specifically, with CVD-related mortality risk. The CRP level may thus be considered a predictive factor in mortality risk scoring algorithms in SSD.

背景：与普通人群相比，精神分裂症谱系障碍（SSD）与更高的死亡风险相关。低级别炎症和c反应蛋白（CRP）水平升高在SSD中已经得到了很好的证实。然而，关于CRP与SSD患者死亡风险之间关系的研究较少。目的探讨SSD患者CRP基线水平与自然原因死亡风险之间的关系。方法：我们纳入了2005年5月1日至2014年6月15日在挪威卑尔根Haukeland大学医院精神病急症病房连续住院的所有SSD诊断和基线CRP测量的患者。所有患者均被随访至死亡或审查/研究结束，随访时间长达18.6年，仅入院时的评估是本研究的重点。使用了一个竞争风险模型，对年龄和性别进行了调整。结果1315例患者中，自然死亡245例（19%）；这些患者中，66例（27%）死亡与心血管疾病（CVD）有关。基线CRP水平升高1.0≤CRP <；3.0 mg/L与自然原因死亡风险增加显著相关（校正危险比[AHR]， 1.88； 95%可信区间[CI]， 1.22-2.88； p值，0.004），与CRP <；1.0 mg/L患者相比，CRP≥3.0 mg/L的相关性更强（AHR, 2.28; 95% CI, 1.50-3.48； p值，<0.001）。此外，基线CRP≥3.0 mg/L与cvd相关死亡风险增加相关（AHR, 3.12; 95% CI, 1.16-8.41； p值，0.024）。结论：CRP水平升高与自然原因死亡率增加有关，特别是与cvd相关的死亡风险有关。因此，CRP水平可能被认为是SSD死亡风险评分算法的预测因素。

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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 Epub Date: 2025-11-22 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

IL-1b and TNF-a-driven sleep alterations: Neuroimmune mechanisms and behavioral implications IL-1b和tnf -a驱动的睡眠改变：神经免疫机制和行为影响

IF 3.5 Q2 IMMUNOLOGY

Brain, behavior, & immunity - health

Pub Date : 2025-12-01 Epub Date: 2025-11-06 DOI: 10.1016/j.bbih.2025.101139

Nathan Zhang , Kyungsoo Park , Shinjae Chung , Yeong Shin Yim

Sleep is a fundamental physiological state essential for immune function, metabolic regulation, and recovery from illness. During infection, sleep patterns are altered in a stereotyped fashion-characterized by increased non-rapid eye movement (NREM) sleep and reduced rapid eye movement (REM) sleep. These sleep changes are not incidental consequences of illness but reflect an evolutionarily conserved neuroimmune adaptation driven by proinflammatory cytokines. In particular, interleukin 1b (IL-1b) and tumor necrosis factor-a (TNFa) modulate sleep by acting directly on central nervous system circuits, including the serotonergic system and homeostatic sleep regulation. In this review, we synthesize current knowledge on how IL-1b and TNFa interact with sleep-regulating networks to alter behavioral state transitions during immune challenge. We also explore the broader clinical relevance of cytokine-driven sleep changes across infectious, psychiatric, and neurodegenerative disorders, and highlight emerging therapeutic opportunities targeting neuroimmune pathways to restore sleep homeostasis. Understanding these interactions is essential for advancing mechanistic insight into sleep regulation and for improving clinical management of inflammation-related sleep disturbances.

睡眠是一种基本的生理状态，对免疫功能、代谢调节和疾病恢复至关重要。在感染期间，睡眠模式以一种刻板的方式改变，其特征是非快速眼动（NREM）睡眠增加，快速眼动（REM）睡眠减少。这些睡眠变化不是疾病的偶然后果，而是反映了由促炎细胞因子驱动的进化保守的神经免疫适应。特别是，白细胞介素1b （IL-1b）和肿瘤坏死因子-a （TNFa）通过直接作用于中枢神经系统回路，包括血清素能系统和稳态睡眠调节来调节睡眠。在这篇综述中，我们综合了目前关于IL-1b和TNFa如何与睡眠调节网络相互作用以改变免疫挑战期间行为状态转变的知识。我们还探讨了细胞因子驱动的睡眠变化在感染性疾病、精神疾病和神经退行性疾病中更广泛的临床相关性，并强调了针对神经免疫途径恢复睡眠稳态的新兴治疗机会。了解这些相互作用对于推进睡眠调节的机制洞察和改善炎症相关睡眠障碍的临床管理至关重要。

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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 Epub Date: 2025-12-02 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

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 Epub Date: 2025-11-27 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 Epub Date: 2025-11-25 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