Brain, Behavior, and Immunity最新文献_第5页

Minimally invasive serial collection of cerebrospinal fluid reveals sex-dependent differences in neuroinflammation in a rat model of mild traumatic brain injury 微创脑脊液系列采集揭示了轻度创伤性脑损伤大鼠模型中神经炎症的性别依赖性差异。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-02-01 DOI: 10.1016/j.bbi.2024.11.015

Josh Karam , Nimrah Ashfaq , Cynthia Benitez , Victor Morales , Elizabeth Partida , Michelle Hernandez , Jordan Yokoyama , Alyssa Villegas , Brielle Brown , Pooja Sakthivel , Aileen J. Anderson , Brian J. Cummings

Traumatic brain injuries (TBI) are the seventh leading cause of disability globally with 48.99 million prevalent cases and 7.08 million years lived with diability. Approximately 80 % of TBI patients are diagnosed with mild TBI (mTBI), or concussion, caused by nonpenetrating mechanical trauma to the head or body along with sudden rotational motion of the head. Studies investigating the temporal dynamics of neuroinflammation after mTBI are greatly needed. Without longitudinal studies, translating preclinical studies to clinical studies remains challenging as the difference in timing remains poorly understood. In this study, we describe a method of minimally invasive serial cerebrospinal fluid (CSF) collection that enables longitudinal investigation of CSF inflammation. The method described in this study can easily be adapted by any laboratory prepared for animal studies. Multiplex immunoassay of serially collected and singly collected CSF samples show collection frequency does not alter protein expression in the CSF. Further, sex-dependent differences in TBI have been reported, but remain poorly understood. This study establishes a framework for assessing sex difference in neuroinflammation after a concussion. We showed that results vary based on the framing of the statistical test. However, it is evident that males experience a more robust inflammatory response to a single concussion than females.

创伤性脑损伤（TBI）是全球第七大致残原因，共有4899万例流行病例和708万年的残疾生活。大约80% %的TBI患者被诊断为轻度TBI (mTBI)，或脑震荡，由头部或身体的非穿透性机械创伤引起，并伴有头部的突然旋转运动。研究mTBI后神经炎症的时间动态是非常必要的。如果没有纵向研究，将临床前研究转化为临床研究仍然具有挑战性，因为对时间的差异仍然知之甚少。在这项研究中，我们描述了一种微创系列脑脊液（CSF）收集方法，该方法可以对CSF炎症进行纵向调查。本研究中描述的方法可以很容易地适用于任何准备进行动物研究的实验室。连续采集和单独采集的脑脊液样品的多重免疫分析显示，采集频率不改变脑脊液中的蛋白质表达。此外，据报道，脑外伤的性别依赖性差异，但仍然知之甚少。本研究建立了一个评估脑震荡后神经炎症的性别差异的框架。我们表明，结果根据统计检验的框架而变化。然而，很明显，男性对一次脑震荡的炎症反应比女性更强烈。

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引用次数: 0

ATP8A2 expression is reduced in the mPFC of offspring mice exposed to maternal immune activation and its upregulation ameliorates synapse-associated protein loss and behavioral abnormalities 暴露于母体免疫激活的后代小鼠mPFC中ATP8A2表达降低，其上调可改善突触相关蛋白丢失和行为异常。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-02-01 DOI: 10.1016/j.bbi.2024.12.018

Wenhui Liu , Kai Yan , Siqi Xu , Lifang Li , Mengdan Zhong , Jing Liu , Guoying Li , Junhua Yang

Prenatal virus infection-induced maternal immune activation (MIA) is linked to a greater risk of neurodevelopmental disorders in offspring. Prenatal exposure to poly(I:C) in pregnant mice is a well-established approach to mimic virus infection-induced MIA, leading to neuropsychiatric disorders and aberrant brain development, especially in the medial prefrontal cortex (mPFC). ATPase phospholipid flippase 8A2 (ATP8A2) is the main phospholipid lipase, expressed in the mPFC and is crucial for maintaining cell membrane stability by flipping phosphatidylserine from the outer leaflet to the inner leaflet of the cell membrane. Atp8a2 knockout or mutation causes a series of phenotypes, including impaired neuronal cell survival, neuroinflammation, altered synaptic plasticity, and behavioral abnormalities. These findings suggest that ATP8A2 expression in the mPFC may be impaired in MIA offspring and that the decrease in ATP8A2 expression may be involved in the development of MIA-induced neuropsychiatric disorders in offspring. No reports addressing this issue have been published. Here, after confirming abnormal affective-/social-related behaviors in adulthood and reduced synapse-associated protein expression on the birth day (P0) and the fourth postnatal day (P4) in the mPFC of MIA offspring that were born to dams exposed prenatally to a single dose of poly(I:C) (10 mg/kg, i.p.), decreased ATP8A2 expression was also observed in the mPFC of MIA offspring at P0 and P4. Upregulating ATP8A2 in the mPFC restored synapse-associated protein levels, along with a partial improvement in the behavioral performance of MIA offspring. Upregulation of ATP8A2 also blocked neuronal phosphatidylserine externalization and eliminated the excitation/inhibition (E/I) imbalance in the mPFC of MIA offspring. This study revealed that the low expression of ATP8A2 following MIA exposure may play a role in mediating abnormal brain development and function in offspring. ATP8A2 potentially represents a novel molecule involved in MIA-induced neuropsychiatric disorders in offspring, and may serve as a novel therapeutic target for the intervention of psychiatric disorders.

产前病毒感染诱导的母体免疫激活（MIA）与后代神经发育障碍的更大风险有关。妊娠小鼠产前暴露于多聚（I:C）是一种成熟的方法来模拟病毒感染诱导的MIA，导致神经精神障碍和大脑异常发育，特别是在内侧前额叶皮层（mPFC）。atp酶磷脂翻转酶8A2 （ATP8A2）是主要的磷脂脂肪酶，在mPFC中表达，通过将磷脂酰丝氨酸从细胞膜的外小叶翻转到细胞膜的内小叶，对维持细胞膜的稳定性至关重要。ATP8A2基因敲除或突变会导致一系列表型，包括神经元细胞存活受损、神经炎症、突触可塑性改变和行为异常。这些发现提示，MIA后代mPFC中ATP8A2的表达可能受损，ATP8A2表达的降低可能与MIA诱导的后代神经精神疾病的发生有关。目前还没有发表关于这个问题的报告。在确认了成年期情感/社会相关行为异常，以及在出生当天（P0）和出生后第4天（P4），暴露于单剂量聚（I:C）（10 mg/kg, i.p.）的MIA后代mPFC中突触相关蛋白表达减少后，在P0和P4时，在MIA后代mPFC中也观察到ATP8A2表达减少。上调mPFC中的ATP8A2可恢复突触相关蛋白水平，并部分改善MIA后代的行为表现。ATP8A2的上调也阻断了神经元磷脂酰丝氨酸外化，消除了MIA后代mPFC中的兴奋/抑制（E/I）失衡。本研究表明，MIA暴露后ATP8A2的低表达可能在介导后代大脑发育和功能异常中起作用。ATP8A2可能代表了一种参与mia诱导的后代神经精神疾病的新分子，并可能作为精神疾病干预的新治疗靶点。

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引用次数: 0

NLRP3 inflammasome mediates astroglial dysregulation of innate and adaptive immune responses in schizophrenia NLRP3炎性体介导精神分裂症先天性和适应性免疫反应的星形胶质细胞失调。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-02-01 DOI: 10.1016/j.bbi.2024.11.030

Attila Szabo , Ibrahim Akkouh , Jordi Requena Osete , Denis Reis de Assis , Elena Kondratskaya , Timothy Hughes , Thor Ueland , Ole A. Andreassen , Srdjan Djurovic

Mounting evidence indicates the involvement of neuroinflammation in the development of schizophrenia (SCZ), but the potential role of astroglia in this phenomenon remains poorly understood. We assessed the molecular and functional consequences of inflammasome activation using induced pluripotent stem cell (iPSC)-derived astrocytes generated from SCZ patients and healthy controls (CTRL). Screening protein levels in astrocytes at baseline identified lower expression of the NLRP3-ASC complex in SCZ, but increased Caspase-1 activity upon specific NLRP3 stimulation compared to CTRL. Using transcriptional profiling, we found corresponding downregulations of NLRP3 and ASC/PYCARD in both iPSC-derived astrocytes, and in a large (n = 429) brain postmortem case-control sample. Functional analyses following NLRP3 activation revealed an inflammatory phenotype characterized by elevated production of IL-1β/IL-18 and skewed priming of helper T lymphocytes (Th1/Th17) by SCZ astrocytes. This phenotype was rescued by specific inhibition of NLRP3 activation, demonstrating its dependence on the NLRP3 inflammasome. Taken together, SCZ iPSC-astrocytes display unique, NLRP3-dependent inflammatory characteristics that are manifested via various cellular functions, as well as via dysregulated innate and adaptive immune responses.

越来越多的证据表明神经炎症参与了精神分裂症（SCZ）的发展，但星形胶质细胞在这一现象中的潜在作用仍然知之甚少。我们使用来自SCZ患者和健康对照（CTRL）的诱导多能干细胞（iPSC）来源的星形胶质细胞来评估炎性小体激活的分子和功能后果。基线星形胶质细胞蛋白水平筛选发现，SCZ中NLRP3- asc复合物的表达较低，但与CTRL相比，特异性NLRP3刺激增加了Caspase-1活性。通过转录谱分析，我们在ipsc衍生的星形胶质细胞和一个大的（n = 429）脑死后病例对照样本中发现NLRP3和ASC/PYCARD的相应下调。NLRP3激活后的功能分析显示，炎症表型的特征是IL-1β/IL-18的产生升高，SCZ星形胶质细胞扭曲启动辅助性T淋巴细胞（Th1/Th17）。这种表型是通过特异性抑制NLRP3激活来挽救的，这表明它依赖于NLRP3炎性体。综上所述，SCZ ipsc -星形胶质细胞显示出独特的nlrp3依赖性炎症特征，这些炎症特征通过各种细胞功能以及失调的先天和适应性免疫反应表现出来。

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引用次数: 0

Dysfunction in neuro-mesenchymal units impairs the development of bone marrow B cells in mice with anxiety 神经间充质单位功能障碍损害焦虑小鼠骨髓B细胞的发育。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-02-01 DOI: 10.1016/j.bbi.2024.12.008

Heshe Li , Junzhe Yi , Xinghao Xu , Yuanchen Ma , Junkai Xiang , Yue Shu , Wenjin Ye , Tao Wang , Jiang Hao , Xiaoran Zhang , Weijun Huang

The reduction in B lymphocytes observed in individuals with anxiety disorders may compromise antiviral responses, yet the precise mechanisms behind this decline remain unclear. While elevated glucocorticoid levels have been suggested as contributing factors, anxiety disorders are associated with diminished glucocorticoid signaling. Given that autonomic nervous system dysfunction is a hallmark of anxiety disorders, we established an anxiety-related behavior mouse model by stimulating C1 neurons in the rostral ventrolateral medulla. Using this model, we confirmed that sustained activation of sympathetic nerves can disrupt adaptive immunity, particularly affecting the development of B cells. The underlying mechanism involves the control of B cell development through neuro-mesenchymal units within the bone marrow, with mesenchyme-derived CXCL12 playing a pivotal role in this regulatory process. Intriguingly, targeting these neuro-mesenchymal units not only restored B cell development but also alleviated anxiety-like behavior in the mice. Our study provides compelling evidence regarding the regulatory role of neuro-mesenchymal units in the development of B cells within the bone marrow. Additionally, our findings suggest that anxiety disorders can create a vicious cycle, perpetuating ongoing mental and immunological damage and ultimately leading to irreversible harm. To break this cycle, it is essential to focus on the dysfunction of immune cells and strive to restore immune homeostasis in individuals suffering from anxiety disorders.

在焦虑症患者中观察到的B淋巴细胞减少可能会影响抗病毒反应，但这种下降背后的确切机制尚不清楚。虽然糖皮质激素水平升高被认为是促成因素，但焦虑症与糖皮质激素信号减弱有关。鉴于自主神经系统功能障碍是焦虑障碍的一个标志，我们通过刺激延髓吻侧腹外侧的C1神经元建立了焦虑相关行为的小鼠模型。通过这个模型，我们证实了持续激活交感神经可以破坏适应性免疫，特别是影响B细胞的发育。其潜在机制涉及通过骨髓内的神经间充质单位控制B细胞的发育，间充质来源的CXCL12在这一调节过程中起关键作用。有趣的是，靶向这些神经间充质单位不仅恢复了B细胞的发育，还减轻了小鼠的焦虑样行为。我们的研究为神经间充质单位在骨髓内B细胞发育中的调节作用提供了令人信服的证据。此外，我们的研究结果表明，焦虑症会造成恶性循环，使正在进行的精神和免疫损伤永久化，最终导致不可逆转的伤害。要打破这种循环，必须关注免疫细胞的功能障碍，努力恢复焦虑症患者的免疫稳态。

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引用次数: 0

Sexual minority stress and epigenetic aging

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-31 DOI: 10.1016/j.bbi.2025.01.022

Lisa M. Christian , Stephanie Wilson , Annelise A. Madison , Claire M. Kamp Dush , Thomas W. McDade , Juan Peng , Rebecca R. Andridge , Ethan Morgan , Wendy Manning , Steve W. Cole

Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ + ) individuals have poorer mental and physical health than heterosexuals, and bisexuals fare worse than individuals who identify as lesbian and gay. However, data on stress biology among sexual minorities are critically insufficient. The current pilot study utilized data from 32 bisexual women – a subset of the National Couples’ Health and Time Study – who completed questionnaires and provided blood samples to index biological aging from DNA methylation data (DunedinPACE, GrimAge2). The mean DunedinPACE score was 1.13 (SD = 0.18), which outpaced chronological aging by 13 % (p < 0.001). Likewise, bisexual women in this sample were, on average, 8.67 (SD = 5.96) years older biologically per GrimAge2 as compared to their chronological age. In covariate adjusted models, those reporting greater internalized homonegativity exhibited significantly greater epigenetic age acceleration (GrimAge2: p = 0.01; DunedinPACE: p = 0.041). Those who reported more frequent anti-bisexual experiences also showed accelerated GrimAge2 (p = 0.023). In contrast, those who reported stronger identity centrality (p = 0.017), stronger identity affirmation (p = 0.029), and more friend support (p = 0.018) – a critical type of support for LGBTQ + individuals – had slower GrimAge2. Depressive symptoms, anxiety and loneliness were not associated with GrimAge2 or DunedinPACE. Results suggest that bisexual women are at risk for accelerated aging, and those who have less internal and external affirmation of their sexual identity may be most at risk.

{"title":"Sexual minority stress and epigenetic aging","authors":"Lisa M. Christian , Stephanie Wilson , Annelise A. Madison , Claire M. Kamp Dush , Thomas W. McDade , Juan Peng , Rebecca R. Andridge , Ethan Morgan , Wendy Manning , Steve W. Cole","doi":"10.1016/j.bbi.2025.01.022","DOIUrl":"10.1016/j.bbi.2025.01.022","url":null,"abstract":"<div><div>Lesbian, gay, bisexual, transgender, and queer/questioning (LGBTQ + ) individuals have poorer mental and physical health than heterosexuals, and bisexuals fare worse than individuals who identify as lesbian and gay. However, data on stress biology among sexual minorities are critically insufficient. The current pilot study utilized data from 32 bisexual women – a subset of the National Couples’ Health and Time Study – who completed questionnaires and provided blood samples to index biological aging from DNA methylation data (DunedinPACE, GrimAge2). The mean DunedinPACE score was 1.13 (SD = 0.18), which outpaced chronological aging by 13 % (p < 0.001). Likewise, bisexual women in this sample were, on average, 8.67 (SD = 5.96) years older biologically per GrimAge2 as compared to their chronological age. In covariate adjusted models, those reporting greater internalized homonegativity exhibited significantly greater epigenetic age acceleration (GrimAge2: p = 0.01; DunedinPACE: p = 0.041). Those who reported more frequent anti-bisexual experiences also showed accelerated GrimAge2 (p = 0.023). In contrast, those who reported stronger identity centrality (p = 0.017), stronger identity affirmation (p = 0.029), and more friend support (p = 0.018) – a critical type of support for LGBTQ + individuals – had slower GrimAge2. Depressive symptoms, anxiety and loneliness were not associated with GrimAge2 or DunedinPACE. Results suggest that bisexual women are at risk for accelerated aging, and those who have less internal and external affirmation of their sexual identity may be most at risk.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"126 ","pages":"Pages 24-29"},"PeriodicalIF":8.8,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078616","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Commentary to the article: “Acute and long-term effects of COVID-19 on brain and mental health: A narrative review”

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-30 DOI: 10.1016/j.bbi.2025.01.017

Andrés Felipe Herrera Ortiz , Laura Manuela Olarte Bermúdez

引用次数: 0

Brain inflammation and cognitive decline induced by spinal cord injury can be reversed by spinal cord cell transplants

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-26 DOI: 10.1016/j.bbi.2025.01.014

Quentin Delarue , Amandine Robac , Fannie Semprez , Célia Duclos , Baptiste Pileyre , Pauline Neveu , Clémence Raimond , Gaëtan Riou , Inès Ziane , Nicolas Guérout

Spinal cord injuries (SCIs) impact between 250,000 and 500,000 people worldwide annually, often resulting from road accidents or falls. These injuries frequently lead to lasting disabilities, with the severity depending on the injury’s extent and location. Emerging research also links SCIs to cognitive impairments due to brain inflammation. From a treatment perspective, various approaches, including cell therapy, have been investigated. One common mechanism across cellular transplant models is the modulation of inflammation at the injury site, though it remains uncertain if these effects extend to the brain. To explore this, we induced SCI in wild-type mice and treated them with either olfactory ensheathing cells or mesenchymal stem cells. Our findings reveal that both cell types can reverse SCI-induced cognitive deficits, reduce brain inflammation, and increase hippocampal neuronal density. This study is the first, to our knowledge, to demonstrate that cells transplanted into the spinal cord can influence brain inflammation and mitigate injury-induced effects on brain functions. These results highlight the intricate relationship between the spinal cord and brain in both health and disease.

{"title":"Brain inflammation and cognitive decline induced by spinal cord injury can be reversed by spinal cord cell transplants","authors":"Quentin Delarue , Amandine Robac , Fannie Semprez , Célia Duclos , Baptiste Pileyre , Pauline Neveu , Clémence Raimond , Gaëtan Riou , Inès Ziane , Nicolas Guérout","doi":"10.1016/j.bbi.2025.01.014","DOIUrl":"10.1016/j.bbi.2025.01.014","url":null,"abstract":"<div><div>Spinal cord injuries (SCIs) impact between 250,000 and 500,000 people worldwide annually, often resulting from road accidents or falls. These injuries frequently lead to lasting disabilities, with the severity depending on the injury’s extent and location. Emerging research also links SCIs to cognitive impairments due to brain inflammation. From a treatment perspective, various approaches, including cell therapy, have been investigated. One common mechanism across cellular transplant models is the modulation of inflammation at the injury site, though it remains uncertain if these effects extend to the brain. To explore this, we induced SCI in wild-type mice and treated them with either olfactory ensheathing cells or mesenchymal stem cells. Our findings reveal that both cell types can reverse SCI-induced cognitive deficits, reduce brain inflammation, and increase hippocampal neuronal density. This study is the first, to our knowledge, to demonstrate that cells transplanted into the spinal cord can influence brain inflammation and mitigate injury-induced effects on brain functions. These results highlight the intricate relationship between the spinal cord and brain in both health and disease.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"125 ","pages":"Pages 388-397"},"PeriodicalIF":8.8,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143058159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reducing IgG accumulation via neonatal Fc receptor (FcRn) blockade relieves neuropathic pain

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-25 DOI: 10.1016/j.bbi.2025.01.015

Nathan T. Fiore , Kendal F. Willcox , Dorsa Dayani , Younus A. Zuberi , Cobi J. Heijnen , Peter M. Grace

Preclinical and clinical studies have established that autoreactive immunoglobulin G (IgG) can drive neuropathic pain. We recently demonstrated that sciatic nerve chronic constriction injury (CCI) in male and female mice results in the production of pronociceptive IgG, which accumulates around the lumbar region, including within the dorsal root ganglia (DRG) and spinal cord, facilitating the development of neuropathic pain. These data raise the intriguing possibility that neuropathic pain may be alleviated by reducing the accumulation of IgG. To this end, we tested whether biologic inhibition or genetic deletion of the neonatal Fc receptor (FcRn) would attenuate mechanical hypersensitivity (allodynia) and IgG deposition induced by CCI. FcRn are prominently expressed on myeloid and endothelial cells and extend the half-life of IgG via pinocytosis and recycling into the extracellular milieu. We show here that administration of the FcRn blocker efgartigimod either 7- or 28-days post-CCI relieved allodynia among both male and female mice, compared to the Fc fragment control. Efgartigimod, administered systemically (intraperitoneal) or to the lumbar region (intrathecal), attenuated mechanical allodynia for at least one month. CCI-induced allodynia was similarly reduced in FcRn-deficient (FcRn^-) mice compared to wild-type mice. Biologic inhibition or genetic deletion of FcRn also reduced CCI-induced accumulation of IgG on macrophages and neurons in lumbar DRG, as well as microglia in the lumbar dorsal spinal cord. Expression of the Fc receptor γ subunit (FcRγ) was reduced in efgartigimod-treated or FcRn^- mice post-CCI compared to controls. The FcRγ subunit is a key component of Fc gamma receptors (FcγRs), which are activated by IgG immune complexes. In macrophage cultures stimulated by IgG immune complexes, FcRn blockade also dampened FcγR-dependent production of proinflammatory cytokines. Collectively, our study demonstrates that FcRn blockade or deletion alleviates mechanical allodynia and reduces IgG accumulation after CCI, attenuating pronociceptive IgG-FcγR signaling around the lumbar region. Strategies to block FcRn and reduce IgG recycling warrant further investigation as potential treatments for IgG-mediated neuropathic pain.

临床前和临床研究已经证实，自身反应性免疫球蛋白 G（IgG）可引起神经性疼痛。我们最近证实，雄性和雌性小鼠坐骨神经慢性收缩损伤（CCI）会导致产生前感觉性 IgG，这种 IgG 会在腰部周围积聚，包括背根神经节（DRG）和脊髓内，从而促进神经性疼痛的发生。这些数据提出了一种耐人寻味的可能性，即通过减少 IgG 的积累来缓解神经性疼痛。为此，我们测试了新生儿 Fc 受体（FcRn）的生物抑制或基因缺失是否会减轻 CCI 诱导的机械过敏（异动症）和 IgG 沉积。FcRn 主要表达于骨髓细胞和内皮细胞，通过针吞作用和向细胞外环境的再循环延长 IgG 的半衰期。我们在此表明，与Fc片段对照组相比，在CCI后7天或28天服用FcRn阻断剂efgartigimod可缓解雄性和雌性小鼠的异动症。与野生型小鼠相比，FcRn缺陷（FcRn-）小鼠的CCI诱导的异动症也同样减轻。FcRn的生物抑制或基因缺失也减少了CCI诱导的巨噬细胞和腰部DRG神经元以及腰部背侧脊髓小胶质细胞上的IgG积聚。与对照组相比，经依加替莫德治疗或CCI后的FcRn-小鼠的Fc受体γ亚基（FcRγ）表达减少。FcRγ亚基是Fcγ受体（FcγRs）的关键组成部分，Fcγ受体由IgG免疫复合物激活。在受到 IgG 免疫复合物刺激的巨噬细胞培养物中，阻断 FcRn 也会抑制 FcγR 依赖性促炎细胞因子的产生。总之，我们的研究表明，阻断或缺失 FcRn 可减轻 CCI 后的机械异感并减少 IgG 累积，从而减弱腰部周围的代痛觉 IgG-FcγR 信号传导。阻断 FcRn 和减少 IgG 循环的策略作为 IgG 介导的神经病理性疼痛的潜在治疗方法值得进一步研究。

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引用次数: 0

Visual cues of respiratory contagion: Their impact on neuroimmune activation and mucosal immune responses in humans

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-25 DOI: 10.1016/j.bbi.2025.01.016

Judith K. Keller , Esther K. Diekhof

This study investigated the neural correlates of perceiving visual contagion cues characteristic of respiratory infections through functional magnetic resonance imaging (fMRI). Sixty-two participants (32f/ 30 m; ∼25 years on average) watched short videos depicting either contagious or non-contagious everyday situations, while their brain activation was continuously measured. We further measured the release of secretory immunoglobulin A (sIgA) in saliva to examine the first-line defensive response of the mucosal immune system. Perceiving sneezing and sick individuals compared to non-contagious individuals triggered increased activation in the anterior insula and other regions of the neuroimmune axis, that have been implicated in the somatosensory representation of the respiratory tract, and further led to increased release of sIgA. In line with predictions, this contagion cue-related activation of the insula was positively correlated with both perceived contagiousness and disgust evoked by the videos, as well as with the mucosal sIgA response. In contrast, the amygdala exhibited heightened activation to all videos featuring humans, regardless of explicit signs of contagion, indicating a nonspecific alertness to human presence. Nevertheless, amygdala activation was also correlated with the disgust ratings of each video. Collectively, these findings outline a neuroimmune mechanism for the processing of respiratory contagion cues. While the insula coordinates central and peripheral immune activation to match the perceived contagion threat, supposedly by triggering both increased sIgA release and contagion-related cognitions, the amygdala may rather act as an alerting system for social situations with a heightened transmission risk. This proactive neuroimmune response may help humans to manage contagion risks, that are difficult to avoid, by activating physiological and cognitive countermeasures in reaction to typical symptoms of respiratory infection, which prepares the organism for subsequent pathogen exposure.

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引用次数: 0

Corrigendum to "Neurofilament light and glial fibrillary acidic protein in mood and anxiety disorders: A systematic review and meta-analysis" [Brain, Behavior, and Immunity 123 (2025) 1091-1102]. 情绪和焦虑症中的神经丝蛋白和胶质纤维酸性蛋白：系统综述和荟萃分析》[Brain, Behavior, and Immunity 123 (2025) 1091-1102]。

IF 8.8 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2025-01-24 DOI: 10.1016/j.bbi.2025.01.004

Matthew J Y Kang, Jasleen Grewal, Dhamidhu Eratne, Charles Malpas, Wei-Hsuan Chiu, Kasper Katisko, Eino Solje, Alexander F Santillo, Philip B Mitchell, Malcolm Hopwood, Dennis Velakoulis

引用次数: 0