Brain, Behavior, and Immunity最新文献_第3页

Corrigendum to "USP9X suppression attenuates NLRP3 inflammasome activation and ameliorates neuroinflammatory phenotypes with motor function recovery in murine models". [Brain Behav. Immun. 132 (2026) 106215]. “在小鼠模型中，USP9X抑制可减弱NLRP3炎性体的激活并改善运动功能恢复的神经炎症表型”的更正。(大脑Behav。免疫学，132(2026)106215]。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-21 DOI: 10.1016/j.bbi.2026.106290

Yu Guo, Xiaochuan Qi, Ao Wang, Tingting Zhan, Kexin Duan, Wenjie Ma, Changqing Liu

引用次数: 0

Corrigendum to "Acute effects of interferon-alpha on cellular anabolic and catabolic processes are associated with the development of fatigue during Interferon-alpha-based therapy for Hepatitis-C: A preliminary study" [Brain Behav. Immun. 123 (2025) 717-724]. “干扰素- α对细胞合成代谢和分解代谢过程的急性影响与干扰素- α治疗丙型肝炎期间疲劳的发展有关：初步研究”的更正[脑行为]。免疫学。123(2025)717-724。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-21 DOI: 10.1016/j.bbi.2026.106287

Eva Periche-Tomas, Annamaria Cattaneo, Nadia Cattane, Claudia Bone, Jeremy Tibble, Edward T Bullmore, Carmine Pariante, Neil A Harrison

引用次数: 0

Longitudinal associations between depression, substance use, and immune activation and inflammation: A secondary analysis of men who have sex with men living with HIV in Brazil (HPTN 063) 抑郁、物质使用、免疫激活和炎症之间的纵向关联：对巴西与艾滋病毒感染者发生性行为的男性的二次分析（HPTN 063）

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-21 DOI: 10.1016/j.bbi.2026.106300

Emily M. Cherenack , Michaela E. Larson , Margaret E. Roach , Daniel J. Feaster , Ruth Khalili Friedman , Steven A. Safren , Adam W. Carrico

Background

Limited research has examined the longitudinal interplay of depression, substance use, and immune dysregulation among men with HIV.

Methods

We analyzed longitudinal data from 100 men who have sex with men (MSM) living with HIV enrolled in the HPTN 063 cohort (2011–2013) in Brazil. Depressive symptom severity, alcohol use severity, and recent illicit stimulant use were assessed quarterly over 12 months. Soluble markers of immune activation (sCD14) and inflammation (IL-6) were measured at baseline and at a 12-month visit.

Results

Depressive symptom severity and alcohol use severity showed substantial within-person variability across time, whereas stimulant use remained relatively stable. These psychosocial factors were weakly intercorrelated. Controlling for baseline IL-6, the odds of having detectable IL-6 at 12 months increased by 2 % for each point increase in the proportion of visits with elevated depression, 7 % for each point increase in mean depressive severity across visits, 5 % for each point increase in depressive severity at nine months, and 6 % for each point increase in depressive severity at 12 months. Effects persisted after controlling for baseline HIV viral load. Controlling for baseline sCD14, estimated 12-month sCD14 increased 8 ng/mL for each point increase in 12-month depressive severity and 20 ng/mL for each point increase in 12-month alcohol use severity. The alcohol–sCD14 association was attenuated when adjusting for HIV viral load. Neither baseline IL-6 nor sCD14 strongly predicted future depressive symptoms or substance use.

Conclusions

Depressive symptoms predicted future inflammation and current immune activation. Research should examine if interventions to treat depression can improve immune functioning.

有限的研究调查了男性HIV感染者中抑郁、药物使用和免疫失调的纵向相互作用。方法：我们分析了巴西HPTN 063队列（2011-2013）中100名感染艾滋病毒的男男性行为者（MSM）的纵向数据。抑郁症状严重程度、酒精使用严重程度和近期非法兴奋剂使用情况在12个月内每季度进行一次评估。在基线和12个月随访时测量可溶性免疫激活标志物（sCD14）和炎症标志物（IL-6）。结果抑郁症状的严重程度和酒精使用的严重程度随时间的变化呈现出显著的个人差异，而兴奋剂的使用保持相对稳定。这些社会心理因素之间的相互关系很弱。控制基线IL-6，在12个月时检测到IL-6的几率在抑郁症升高的就诊比例中每增加一点增加2%，在就诊期间平均抑郁严重程度每增加一点增加7%，在9个月时抑郁严重程度每增加一点增加5%，在12个月时抑郁严重程度每增加一点增加6%。在控制基线HIV病毒载量后，效果持续存在。对照基线sCD14, 12个月抑郁严重程度每增加一个点，估计sCD14增加8 ng/mL， 12个月酒精使用严重程度每增加一个点，估计sCD14增加20 ng/mL。当调整HIV病毒载量时，酒精与scd14的关联减弱。基线IL-6和sCD14都不能强烈预测未来的抑郁症状或药物使用。结论抑郁症状预示着未来的炎症和当前的免疫激活。研究应该检查治疗抑郁症的干预措施是否能改善免疫功能。

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引用次数: 0

Insights into mesenchymal stem/stromal cell conditioned media as a long-lasting treatment for pain and psychiatric comorbidities in a murine model of osteoarthritis 间充质干细胞/基质细胞条件介质作为骨关节炎小鼠模型疼痛和精神合并症的长期治疗的见解

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-20 DOI: 10.1016/j.bbi.2026.106297

Giada Amodeo , Stefania Niada , Giulia Galimberti , Silvia Franchi , Elena Della Morte , Michela Taiana , Simona Piccolo , Stefania Ceruti , Laura de Girolamo , Anna Teresa Brini , Paola Sacerdote

Osteoarthritis (OA) is a prevalent musculoskeletal condition characterized by chronic pain and often accompanied by psychiatric comorbidities, such as anxiety and depression. The mesenchymal/stromal cell (MSC) secretome has emerged as promising therapy due to its immunomodulatory and regenerative properties. This study aimed to compare the therapeutic efficacy of standard (CM) and cytokine-primed conditioned media (CM⁺) derived from human adipose-derived MSCs in mitigating pain, mood alterations and neuroinflammation in a murine OA model. OA was induced by intra-articular injection of monoiodoacetate in male C57BL/6J mice. On day 7, mice received a single intravenous dose of CM or CM⁺ at two concentrations. Pain-related behavior was assessed by mechanical and thermal nociceptive tests. Anxiety- and depression-like behaviors were evaluated through open field, light/dark box, and forced swim tests. Pro- and anti-inflammatory cytokines and (neuro)inflammatory markers were analyzed in OA joint, and in the peripheral and central nervous system. Peripheral innervation and substance P were assessed in OA paw skin. Both CM and CM⁺ reduced painful and affective symptoms in a dose-dependent manner. However, CM (from non-primed MSCs) exhibited faster onset and longer-lasting effects, up to 17 days post-injection, compared to CM⁺.

CM also led to greater improvements in neuroinflammatory profiles, rebalancing cytokine pattern and macrophage polarization across peripheral and central tissues. MSC secretome, especially when generated without inflammatory priming, represents a safe and long-lasting therapeutic option for OA pain and associated mood disorders. These findings highlight its clinical potential as an innovative multi-targeted biological therapy.

骨关节炎（OA）是一种常见的肌肉骨骼疾病，以慢性疼痛为特征，常伴有精神合并症，如焦虑和抑郁。间充质/基质细胞（MSC）分泌组由于其免疫调节和再生特性而成为一种有前景的治疗方法。本研究旨在比较标准（CM）和来源于人脂肪来源的MSCs的细胞因子启动条件培养基（CM+）在减轻小鼠OA模型疼痛、情绪改变和神经炎症方面的治疗效果。用单碘乙酸酯关节内注射诱导雄性C57BL/6J小鼠骨性关节炎。第7天，小鼠接受单次静脉注射CM或两种浓度的CM+。通过机械和热伤害性测试评估疼痛相关行为。通过开场、光/暗盒和强迫游泳测试评估焦虑和抑郁样行为。分析OA关节、外周和中枢神经系统的促炎性和抗炎性细胞因子及（神经）炎症标志物。评估OA足跖皮肤的外周神经支配和P物质。CM和CM+均以剂量依赖的方式减轻疼痛和情感症状。然而，与CM+相比，CM（来自非引物MSCs）在注射后17 天内表现出更快的起效和更持久的效果。CM还导致神经炎症谱的更大改善，再平衡细胞因子模式和外周和中枢组织的巨噬细胞极化。MSC分泌组，特别是在没有炎症启动的情况下产生，代表了OA疼痛和相关情绪障碍的安全和持久的治疗选择。这些发现突出了其作为一种创新的多靶点生物疗法的临床潜力。

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引用次数: 0

Corrigendum to "Social factors as buffers for the adverse impact of adverse childhood experiences on biological age acceleration among adults in Hispanic Community Health Study/Study of Latinos" [Brain Behav. Immun. 132 (2026) 106241]. “社会因素作为缓冲不良童年经历对西班牙裔社区健康研究/拉丁裔研究中成年人生理年龄加速的不利影响”[脑行为]的更正。免疫学，132(2026)106241]。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-20 DOI: 10.1016/j.bbi.2026.106289

Yinxian Chen, Sarina Abrishamcar, Jasmine K Aqua, Christian Dye, Linda C Gallo, Maria M Llabre, Frank J Penedo, Carmen R Isasi, Krista M Perreira, Bharat Thyagarajan, Martha Daviglus, Amber Pirzada, Andrea Baccarelli, Karen N Conneely, Rebecca Jones-Antwi, Shakira F Suglia

引用次数: 0

An extraverted behavior intervention improves immune gene expression 外倾性行为干预可改善免疫基因表达。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-20 DOI: 10.1016/j.bbi.2026.106299

Ramona L. Martinez , Sonja Lyubomirsky , Steve W. Cole

Background

Social connection is critical to both psychological well-being and optimal immune function. The present study tested whether a behavioral intervention to increase social connection (promoting extraverted behavior) might reduce a threat-related immunoregulatory gene expression program known as the Conserved Transcriptional Response to Adversity (CTRA). The CTRA is characterized by elevated inflammatory gene expression and reduced innate antiviral gene expression in response to beta adrenergic signaling and has been associated with adverse social conditions such as loneliness and ostracism.

Methods

In an 8-week intervention (with 6-week behavior change protocol), participants from a campus community (N = 119; 87 % undergraduate; 9 % graduate; 4 % staff) were randomized to act more extraverted (sociable; Extraversion condition) or track routine daily activities (Control condition). Participants reported on psychological outcomes and provided dried blood spots for RNA sampling at pre-test (Week 0), post-test (Week 8), and 1-month follow-up (Week 12). Multilevel models tested condition differences in CTRA expression over time and examined mediation via psychological outcomes.

Results

Pre-registered analyses of pre-specified CTRA indicator genes showed no significant effects. Secondary genome-wide bioinformatic analyses of NF-κB, IRF, and CREB transcription control pathways found significantly greater reductions in CTRA-characteristic gene regulation among the Extraversion group relative to controls. These effects were partially mediated by reductions in loneliness. However, the intervention effect on CTRA gene regulation was not sustained at 1-month follow-up.

Implications

Extraverted behavior may improve immune regulation by enhancing perceived social connection. Further research should replicate these findings and enhance the durability of effects.

背景：社会联系对心理健康和最佳免疫功能都至关重要。本研究测试了增加社会联系的行为干预（促进外向行为）是否会减少与威胁相关的免疫调节基因表达程序，即逆境保守转录反应（CTRA）。CTRA的特点是炎症基因表达升高，先天抗病毒基因表达减少，以响应β肾上腺素能信号，并与不良的社会条件，如孤独和排斥有关。方法：在为期8周的干预（采用6周的行为改变方案）中，来自校园社区的参与者（N = 119；87 %本科生；9 %研究生；4 %教职员工）被随机分配为表现更外向（社交；外向条件）或跟踪日常活动（对照条件）。参与者报告心理结果，并在测试前（第0周）、测试后（第8周）和1个月的随访（第12周）提供干血点用于RNA取样。多水平模型测试了CTRA表达随时间的条件差异，并通过心理结果检验了中介作用。结果：预先注册的CTRA指标基因分析显示无显著影响。对NF-κB、IRF和CREB转录控制途径的二次全基因组生物信息学分析发现，与对照组相比，外倾组的ctra特征基因调控显著降低。这些影响部分是由孤独感的减少所介导的。然而，在1个月的随访中，对CTRA基因调控的干预效果并未持续。启示：外向行为可能通过增强感知的社会联系来改善免疫调节。进一步的研究应重复这些发现，并提高效果的持久性。

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引用次数: 0

Dickkopf-1 release by the bone marrow upon ischemic stroke bridges neurovascular and immune deregulations. 骨髓中Dickkopf-1的释放在缺血性中风中架起了神经血管和免疫失调的桥梁。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-19 DOI: 10.1016/j.bbi.2026.106294

Romain Menet, Maxime Bernard, Sarah Lecordier, Esther Trudel, Anne-Sophie Allain, Félix Distéfano-Gagné, Josée Seigneur, Natija Aldib, Yacine Haili, Frédéric Bretzner, David Gosselin, Ayman ElAli

Neurovascular and immune alterations decisively govern definitive damage maturation after stroke. Dickkopf (DKK)1 elevated levels in the blood circulation of stroke patients correlate with poor outcomes. Herein, we report that Dkk1 mRNA expression is not endogenously expressed in the healthy brain and is barely and sparsely detectable at the lesion site in experimental ischemic stroke. Notably, we reveal a progressive increased protein expression of DKK1 in the subacute phase. Using genetic tools and bone marrow replacement approaches to mediate conditional DKK1 tissue-specific induction in conjunction with imaging, molecular, transcriptomic and functional studies, we demonstrate that DKK1 high levels at stroke onset accelerate subacute injury progression via deregulation of neurovascular functions. DKK1 prolonged post-stroke elevated levels mediate a chronic neuroinflammation associated with anxiety-like behaviors. DKK1 restricted induction in the bone marrow is sufficient to accelerate the subacute damage progression. DKK1 modulates the subacute peripheral immune response, suggesting that its de novo bone marrow expression represents a novel mechanism to modulate hematopoiesis in response to stroke. Neutralization of DKK1's biological activity improves stroke outcomes. Our results indicate that DKK1 bone marrow release is a major determinant of definitive damage maturation after stroke and that its neutralization constitutes a promising disease-modifying therapeutic avenue.

神经血管和免疫改变决定性地控制中风后的最终损伤成熟。卒中患者血液循环中Dickkopf (DKK)1水平升高与预后不良相关。在本文中，我们报道了Dkk1 mRNA的表达在健康大脑中不是内源性表达的，并且在实验性缺血性脑卒中的病变部位几乎可以检测到。值得注意的是，我们揭示了亚急性期DKK1蛋白表达的进行性增加。结合影像学、分子学、转录组学和功能研究，我们利用遗传工具和骨髓替代方法介导条件性DKK1组织特异性诱导，证明中风发作时DKK1高水平通过神经血管功能的失调加速亚急性损伤的进展。卒中后DKK1水平延长升高介导与焦虑样行为相关的慢性神经炎症。DKK1在骨髓中的限制性诱导足以加速亚急性损伤的进展。DKK1调节亚急性外周免疫反应，表明其新生骨髓表达代表了一种新的机制来调节中风反应中的造血。中和DKK1的生物活性可改善脑卒中预后。我们的研究结果表明，DKK1骨髓释放是卒中后决定性损伤成熟的主要决定因素，其中和构成了一种有希望的疾病改善治疗途径。

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引用次数: 0

Sex-dependent protective effects of a ketogenic diet following prenatal stress exposure: Evidence from adolescent rats 产前应激暴露后生酮饮食的性别依赖性保护作用：来自青春期大鼠的证据。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-19 DOI: 10.1016/j.bbi.2026.106301

Veronica Begni , Alessia Marchesin , Rodrigo Orso , Kerstin Camile Creutzberg , Federica Precetti , Annamaria Cattaneo , Marco Andrea Riva

Exposure to stress during gestation (prenatal stress, PNS) disrupts neurodevelopmental trajectories and increases vulnerability to neuropsychiatric disorders, through dysregulation of different molecular pathways. PNS-induced alterations frequently emerge during adolescence, a highly dynamic maturational period, highlighting a critical window in which therapeutic interventions may modify pathological outcomes. Here, we investigated whether a post-weaning ketogenic diet (KD) could modulate PNS-induced behavioral and molecular alterations in adolescent Sprague–Dawley rats. At weaning offspring from dams exposed to repeated restraint stress during gestation were assigned to a control diet (CD) or KD. Behavioral testing was conducted during adolescence, and prefrontal cortex (PFC) was analyzed for excitatory/inhibitory markers, redox regulators, and inflammatory mediators. PNS induced sociability deficits that were ameliorated by KD. A two-step cluster analysis identified ∼50–55 % of PNS offspring as “vulnerable,” whereas KD reduced this proportion to 22 % in males and 12 % in females. At the molecular level, KD exerted sex-dependent effects in the PFC: in males, it enhanced inhibitory interneuron markers and reduced pro-inflammatory transcripts while altering NRF2/KEAP1 redox signaling; in females, it increased NRF2 and partially restored GCLC1, while PNS selectively disrupted inhibitory and excitatory markers. Together, these findings demonstrate that post-weaning KD rescues PNS-induced social deficits and reshapes PFC molecular profiles, engaging sex-specific mechanisms of resilience. In summary, diet-based interventions during adolescence may represent a promising strategy to counteract developmental stress-related vulnerability.

妊娠期暴露于压力（产前压力，PNS）会破坏神经发育轨迹，并通过不同分子通路的失调增加对神经精神疾病的易感性。pns诱导的改变经常出现在青春期，这是一个高度动态的成熟期，突出了治疗干预可能改变病理结果的关键窗口期。在这里，我们研究了断奶后生酮饮食（KD）是否可以调节青春期Sprague-Dawley大鼠pns诱导的行为和分子改变。在断奶时，在妊娠期间暴露于反复约束应激的母鼠的后代被分配到对照饲粮（CD）或KD。在青少年时期进行行为测试，并分析前额皮质（PFC）的兴奋/抑制标志物、氧化还原调节剂和炎症介质。PNS诱导的社交能力缺陷通过KD得到改善。两步聚类分析确定约50-55 %的PNS后代是“易感的”，而KD将这一比例在雄性中降低到22 %，在雌性中降低到12 %。在分子水平上，KD在PFC中发挥了性别依赖的作用：在雄性中，它增强了抑制性神经元间标记物，减少了促炎转录物，同时改变了NRF2/KEAP1氧化还原信号；在雌性中，它增加了NRF2并部分恢复了GCLC1，而PNS选择性地破坏了抑制性和兴奋性标志物。综上所述，这些研究结果表明，断奶后KD可缓解pns诱导的社会缺陷，重塑PFC分子图谱，参与性别特异性的恢复机制。总之，青少年时期以饮食为基础的干预可能是一种很有希望的策略，可以抵消发育压力相关的脆弱性。

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引用次数: 0

Inhibition of the NFATc2/FKBP5 axis alleviates microglial neuroinflammation by regulating arachidonic acid metabolism in Parkinson’s disease 抑制NFATc2/FKBP5轴通过调节花生四烯酸代谢减轻帕金森病的小胶质神经炎症

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-18 DOI: 10.1016/j.bbi.2026.106296

Yao Si , Xue Zhao , Lei Wu , Xueying Li , Pusheng Quan , Shi Yan , Xinyu Zhang , Lige Han , Lifen Yao , Fan Yang

Microglia-induced neuroinflammation is among the core pathological hallmarks of Parkinson’s disease (PD). FKBP5, which has been implicated in stress-related disorders, is recognized as a key regulator of inflammatory responses. However, the role and mechanism of FKBP5 in PD remain unclear. In the present study, we revealed that reducing FKBP5 levels via shRNA targeting microglia or pharmacological inhibition with SAFit2 could mitigate motor impairment and dopamine neuronal loss, as well as reduce arachidonic acid (AA) and proinflammatory factors (IL-6, TNF-α, and iNOS) levels in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice. Conversely, FKBP5 knockdown in 1-methyl-4-phenylpyridinium (MPP⁺)-treated BV2 microglia reduced inflammatory marker expression and targeted the inhibition of AA synthesis. Moreover, we revealed that NFATc2, a transcription factor of FKBP5, was significantly involved in AA generation and proinflammatory cytokine expression both in vivo and in vitro. In the MPP⁺-treated microglia, FKBP5 upregulation reversed the inhibition of AA signaling pathways induced by NFATc2 silencing. Furthermore, PD patients presented elevated mRNA expression of NFATc2 and FKBP5 in the peripheral blood, which were positively correlated with disease severity and serum AA levels, respectively. These findings highlight the involvement of the NFATc2/FKBP5 signaling pathway in AA-induced microglial neuroinflammation, indicating that NFATc2/FKBP5 may serve as PD biomarkers and targets for therapeutic interventions.

小胶质细胞诱导的神经炎症是帕金森病（PD）的核心病理标志之一。FKBP5与应激相关疾病有关，被认为是炎症反应的关键调节因子。然而，FKBP5在PD中的作用和机制尚不清楚。在本研究中，我们发现通过shRNA靶向小胶质细胞或药理抑制SAFit2降低FKBP5水平可以减轻1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理小鼠的运动损伤和多巴胺神经元丢失，并降低花生四烯酸（AA）和促炎因子（IL-6， TNF-α和iNOS）水平。相反，FKBP5在1-甲基-4-苯基吡啶（MPP+）处理的BV2小胶质细胞中下调，可降低炎症标志物的表达，并靶向抑制AA合成。此外，我们发现FKBP5的转录因子NFATc2在体内和体外均显著参与AA的产生和促炎细胞因子的表达。在MPP+处理的小胶质细胞中，FKBP5上调逆转了NFATc2沉默诱导的AA信号通路的抑制。PD患者外周血中NFATc2和FKBP5 mRNA表达升高，分别与疾病严重程度和血清AA水平呈正相关。这些发现强调了NFATc2/FKBP5信号通路参与aa诱导的小胶质神经炎症，表明NFATc2/FKBP5可能作为PD生物标志物和治疗干预的靶点。

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引用次数: 0

Discovery of novel blood–brain barrier neuropathology in schizophrenia and bipolar disorder midbrain 精神分裂症和双相情感障碍中脑新血脑屏障神经病理的发现。

IF 7.6 2区医学 Q1 IMMUNOLOGY

Brain, Behavior, and Immunity

Pub Date : 2026-01-18 DOI: 10.1016/j.bbi.2026.106292

Yunting Zhu , Gerardo Mendez Victoriano , Maree J Webster , Frank A. Middleton , Paul T. Massa , Christine Fuller , Cynthia Shannon Weickert

Elevated pro-inflammatory cytokines and increased macrophage densities have been found in ∼ 35–50 % of schizophrenia and bipolar disorder brains. However, the influence of neuroinflammation on the blood–brain barrier (BBB) in these serious mental illnesses remains unclear. Here, we measured and compared multiple BBB-associated molecules in the ventral midbrain, including chemokines, macrophage markers, adhesion molecules, tight junction proteins, and basement membrane proteins in people with schizophrenia (n = 35), or bipolar disorder (n = 34), and controls (n = 33), stratified by inflammatory status. Both mRNA and protein levels of macrophage chemokine (CCL2) and macrophage scavenger receptor (CD163) were significantly elevated in the neuroinflammatory schizophrenia (high) compared to all the low inflammatory subgroups. Adhesion molecule mRNAs (ICAM1 and PECAM1) were increased in both schizophrenia and bipolar disorder high inflammatory subgroups, but PECAM1 protein was only elevated in schizophrenia, while ICAM1 protein was decreased in bipolar disorder. We found lower collagen IV (ColIV) protein levels in bipolar disorder. Tight junction protein claudin-5 (CLDN5) mRNA was elevated in both schizophrenia and bipolar disorder high inflammatory subgroups, while occludin (OCLN) mRNA was decreased in schizophrenia, especially in the high inflammatory subgroup. CLDN5 immunostaining revealed increased fragmented blood vessels with bursts of CLDN5 + processes surrounding and appearing to emanate from endothelial cells in schizophrenia and bipolar disorder high inflammation subgroup. Collectively, the high inflammatory individuals in both schizophrenia and/or bipolar disorder display more signs of BBB alterations, including increased macrophage chemoattraction, changed adhesion molecules, and altered tight junction proteins, though they have distinct molecular signatures of BBB pathology in the midbrain.

在 ~ 35 ~ 50% %的精神分裂症和双相情感障碍患者的大脑中发现了升高的促炎细胞因子和巨噬细胞密度。然而，在这些严重的精神疾病中，神经炎症对血脑屏障（BBB）的影响尚不清楚。在这里，我们测量并比较了精神分裂症患者（n = 35）或双相情感障碍患者（n = 35）和对照组（n = 33）中脑腹侧多种血脑屏障相关分子，包括趋化因子、巨噬细胞标志物、粘附分子、紧密连接蛋白和基底膜蛋白，并按炎症状态分层。与所有低炎症亚组相比，神经炎性精神分裂症（高）患者巨噬细胞趋化因子（CCL2）和清除率受体（CD163）的mRNA和蛋白水平均显著升高。粘附分子mrna （ICAM1和PECAM1）在精神分裂症和双相情感障碍高炎症亚组中均升高，但PECAM1蛋白仅在精神分裂症中升高，而ICAM蛋白在双相情感障碍中降低。我们发现双相情感障碍患者胶原蛋白IV （ColIV）水平较低。紧密连接蛋白CLDN5 (CLDN5) mRNA在精神分裂症和双相情感障碍高炎症亚组中均升高，而occludin (OCLN) mRNA在精神分裂症，特别是在高炎症亚组中均降低。CLDN5免疫染色显示，在精神分裂症和双相情感障碍高炎症患者中，血管碎片增加，伴有CLDN5 + 突的破裂，并似乎来自内皮细胞。总的来说，精神分裂症和/或双相情感障碍的高炎症个体显示出更多血脑屏障改变的迹象，包括巨噬细胞化学吸引增加，粘附分子改变，紧密连接蛋白改变，尽管他们在中脑有不同的血脑屏障病理分子特征。

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引用次数: 0