Brain, Behavior, and Immunity最新文献

{"title":"Inhibition of TrkB-BDNF positive feedback loop attenuates intervertebral disc degeneration and low back pain in a composite mouse model","authors":"Xiang Ao ,&nbsp;Kun Li ,&nbsp;Yujie Chen ,&nbsp;Weiyi Lai ,&nbsp;Zhengnan Lian ,&nbsp;Zhengnong Wei ,&nbsp;Liang Wang ,&nbsp;Zhongmin Zhang ,&nbsp;Minjun Huang","doi":"10.1016/j.bbi.2025.03.029","DOIUrl":"10.1016/j.bbi.2025.03.029","url":null,"abstract":"<div><div>Intervertebral disc degeneration (IVDD) is a significant contributor to low back pain (LBP); however, the specific mechanisms involved remain unclear. Herein, a novel LBP mouse model was developed by integrating a bipedal standing model with a lumbar spine instability model (BS + LSI). This model effectively reproduced the behavioral characteristics of LBP and the pathological features of IVDD. Notably, a higher degree of degeneration and innervation in the endplates were observed in the BS + LSI mice. Transcriptome analysis revealed a significant upregulation of Ntrk2, the gene encoding TrkB, in the intervertebral discs of BS + LSI mice. Immunohistochemical staining further confirmed elevated expression of TrkB and its ligand BDNF in the endplates of these mice. Moreover, cyclic tensile strain (CTS) (20 %, 0.1 Hz, 24 h) upregulated TrkB expression and activated NF-κB signaling pathway to promote inflammatory responses in endplate chondrocytes. siBDNF transfection or treatment with the TrkB inhibitor ANA-12 effectively inhibited these pathological changes. Mechanistically, TrkB promoted BDNF expression by enhancing CREB phosphorylation, thereby establishing a TrkB-CREB-BDNF positive feedback loop. In vivo injection of ANA-12 significantly alleviated endplate inflammation and LBP-related behaviors in BS + LSI mice. Thus, an effective and replicable mouse model of LBP was established to identify TrkB as both the receptor for and an upstream regulator of BDNF, making it a crucial target for interventions to alleviate CEP inflammation and LBP.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 37-53"},"PeriodicalIF":8.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728658","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of Nuclear Factor-kappa B in the nucleus accumbens core is necessary for chronic stress-induced glutamate and neuro-immune alterations that facilitate cocaine self-administration","authors":"Bethania Mongi-Bragato ,&nbsp;Marianela Adela Sánchez ,&nbsp;María Paula Avalos ,&nbsp;María Julieta Boezio ,&nbsp;Andrea Susana Guzman ,&nbsp;Diana Rigoni ,&nbsp;Eduardo Marcelo Perassi ,&nbsp;Carlos Ruben Mas ,&nbsp;Mariano Bisbal ,&nbsp;Flavia Andrea Bollati ,&nbsp;Liliana Marina Cancela","doi":"10.1016/j.bbi.2025.03.028","DOIUrl":"10.1016/j.bbi.2025.03.028","url":null,"abstract":"<div><div>Stressful events are associated with impaired glutamate signaling and neuroimmune adaptations that may increase the vulnerability of individuals to cocaine addiction. We previously demonstrated that chronic stress induced reactive microglia and increased TNF-α expression in the nucleus accumbens core (NAcore), both alterations strongly linked with impaired glutamate homeostasis and the facilitation of cocaine self-administration. The nuclear factor kappa-B (NF-κB) is a critical regulator of many immune- and addiction-related genes, such as the gene coding for glutamate transporter (GLT-1), and it is considered a master regulator of inflammation, reported to be a key driver of microglia activation in psychiatric diseases. However, no studies have examined the role of NF-κB signaling within the NAcore in the neuroimmune and glutamate mechanism, underpinning stress-induced vulnerability to cocaine self-administration. Here we investigate whether viral dominant negative inhibition of I kappa B kinase (IKKdn), a signaling molecule responsible for NF-κB activation, would prevent stress-induced facilitation to cocaine self-administration and associated changes in accumbal GLT-1 and TNF-α expression. We also explore N-myc proto-oncogene protein (N-myc) levels as a link between NF-κB and stress-induced GLT-1 downregulation. For seven days (days 1–7), adult male rats were restrained for 2 h/day. Animals were administered an intra-NAcore with IKKdn or empty lentiviruses on day 14 after the first restraint stress session. Marked activation of NF-κB was detected in the NAcore of stressed subjects, along with increased NF-κB expression in astrocytes. Consistently, viral NF-κB inhibition prevented stress-induced facilitation of cocaine self-administration. Moreover, NF-κB blockade results in the restoration of stress-induced reduction in GLT-1 levels and was effective in suppressing stress-induced TNF-α within the NAcore. These findings suggest that accumbal NF-κB signaling exerts a central control over stress-altered downstream neuroimmune and glutamate function underlying vulnerability to cocaine use disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 1-15"},"PeriodicalIF":8.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143728577","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"L-tyrosine alleviates autism-like behavior in mice by remodeling the gut microbiota","authors":"Jingjing Fang ,&nbsp;Jingya Guo ,&nbsp;Yujie Lao ,&nbsp;Seong-Gook Kang ,&nbsp;Kunlun Huang ,&nbsp;Tao Tong","doi":"10.1016/j.bbi.2025.03.025","DOIUrl":"10.1016/j.bbi.2025.03.025","url":null,"abstract":"<div><div>Autism spectrum disorder (ASD) is characterized by impaired social interaction and repetitive stereotyped behavior, and effective interventions for the core autistic symptoms are currently limited. This study examines the protective role of L-tyrosine in alleviating ASD-like behavioral disorders in a valproic acid (VPA)-induced ASD mouse model and explores the underlying mechanisms via integrated multi-omics. We first investigated the potential of dietary L-tyrosine in mitigating autistic behavior. Subsequently, 16S rRNA sequencing, hippocampal transcriptomics, and neurotransmitter metabolome were employed to elucidate the underlying mechanism. Further, we conducted transplantation of the L-tyrosine-regulated microbiota in VPA-induced ASD mice. The results showed that L-tyrosine supplementation significantly mitigates ASD-like behavioral disorders, alleviates social communication deficits, and reduces repetitive behavior in autistic mice. L-tyrosine also attenuates the neuronal loss caused by VPA treatment in the DG and CA1 hippocampal regions in mice. The hippocampi of the L-tyrosine-treated mouse model for ASD displays modified gene expression profiles and different neurotransmitter levels. L-tyrosine also mitigates colonic barrier damage and amends the gut microbial composition and function. The integrative transcriptomic, metabolomic, and microbiome analysis shows strong connections between the hippocampal genes, neurotransmitters, and gut microbiota affected by L-tyrosine. The transplantation of microbiota from L-tyrosine-treated mice to VPA-induced ASD mice recipients recapitulated the preventive and protective effects of L-tyrosine on autistic behavior disorders. These findings suggest that dietary L-tyrosine may represent a viable, effective treatment option for managing the physiological and behavioral deficits associated with ASD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 358-374"},"PeriodicalIF":8.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691249","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuropsychiatric sequelae in an experimental model of post-COVID syndrome in mice","authors":"Jordane Clarisse Pimenta ,&nbsp;Vinícius Amorim Beltrami ,&nbsp;Bruna da Silva Oliveira ,&nbsp;Celso Martins Queiroz-Junior ,&nbsp;Jéssica Barsalini ,&nbsp;Danielle Cunha Teixeira ,&nbsp;Luiz Pedro de Souza-Costa ,&nbsp;Anna Luiza Diniz Lima ,&nbsp;Caroline Amaral Machado ,&nbsp;Bárbara Zuccolotto Schneider Guimarães Parreira ,&nbsp;Felipe Rocha da Silva Santos ,&nbsp;Pedro Augusto Carvalho Costa ,&nbsp;Larisse de Souza Barbosa Lacerda ,&nbsp;Matheus Rodrigues Gonçalves ,&nbsp;Ian de Meira Chaves ,&nbsp;Manoela Gonzaga Gontijo Couto ,&nbsp;Victor Rodrigues de Melo Costa ,&nbsp;Natália Ribeiro Cabacinha Nóbrega ,&nbsp;Bárbara Luísa Silva ,&nbsp;Talita Fonseca ,&nbsp;Vivian Vasconcelos Costa","doi":"10.1016/j.bbi.2025.03.022","DOIUrl":"10.1016/j.bbi.2025.03.022","url":null,"abstract":"<div><div>The global impact of the COVID-19 pandemic has been unprecedented, and presently, the world is facing a new challenge known as post-COVID syndrome (PCS). Current estimates suggest that more than 100 million people are grappling with PCS, encompassing several manifestations, including pulmonary, musculoskeletal, metabolic, and neuropsychiatric sequelae (cognitive and behavioral). The mechanisms underlying PCS remain unclear. The present study aimed to: (i) comprehensively characterize the acute effects of pulmonary inoculation of the betacoronavirus MHV-A59 in immunocompetent mice at clinical, cellular, and molecular levels; (ii) examine potential acute and long-term pulmonary, musculoskeletal, and neuropsychiatric sequelae induced by the betacoronavirus MHV-A59; and to (iii) assess sex-specific differences. Male and female C57Bl/6 mice were initially inoculated with varying viral titers (3x10³ to 3x10⁵ PFU/30 μL) of the betacoronavirus MHV-A59 via the intranasal route to define the highest inoculum capable of inducing disease without causing mortality. Further experiments were conducted with the 3x10⁴ PFU inoculum. Mice exhibited an altered neutrophil/lymphocyte ratio in the blood in the 2nd and 5th day post-infection (dpi). Marked lung lesions were characterized by hyperplasia of the alveolar walls, infiltration of polymorphonuclear leukocytes (PMN) and mononuclear leukocytes, hemorrhage, increased concentrations of CCL2, CCL3, CCL5, and CXCL1 chemokines, as well as high viral titers until the 5th dpi. While these lung inflammatory signs resolved, other manifestations were observed up to the 60 dpi, including mild brain lesions with gliosis and hyperemic blood vessels, neuromuscular dysfunctions, anhedonic-like behavior, deficits in spatial working memory, and short-term aversive memory. These musculoskeletal and neuropsychiatric complications were exclusive to female mice and prevented after ovariectomy. In summary, our study describes for the first time a novel sex-dependent model of PCS focused on neuropsychiatric and musculoskeletal disorders. This model provides a unique platform for future investigations regarding the effects of acute therapeutic interventions on the long-term sequelae unleashed by betacoronavirus infection.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 16-36"},"PeriodicalIF":8.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Inflammation and psychomotor retardation in depression: The moderating role of glymphatic system","authors":"Qunjun Liang ,&nbsp;Bo Peng ,&nbsp;Shengli Chen ,&nbsp;Hongyue Wei ,&nbsp;Shiwei Lin ,&nbsp;Xiaoshan Lin ,&nbsp;Ying Li ,&nbsp;Yingli Zhang ,&nbsp;Zhifeng Zhou ,&nbsp;Ziyun Xu ,&nbsp;Gangqiang Hou ,&nbsp;Yingwei Qiu","doi":"10.1016/j.bbi.2025.03.024","DOIUrl":"10.1016/j.bbi.2025.03.024","url":null,"abstract":"<div><h3>Background</h3><div>Psychomotor retardation (PMR) is a predominant symptom in patients with major depressive disorder (MDD). The relationship between inflammation and PMR is the subject of ongoing debate. The glymphatic system (GS) is a waste clearance system in the brain that interacts with the immune system. Herein, we hypothesized that GS function moderates the association between inflammation and PMR.</div></div><div><h3>Methods</h3><div>A total of 67 patients with MDD and 67 healthy controls (HCs) were recruited and underwent MRI scanning. PMR and inflammation, which were evaluated by measuring high-sensitivity C-reactive protein (hsCRP) levels in peripheral blood, were assessed in all patients. Diffusion tensor imaging analysis along the perivascular space was used to assess GS function. Functional connectivity (FC) and morphology within the motor circuit were also assessed. Moderation models were constructed to estimate the effect of GS function as a moderator of the relationships between hsCRP level and PMR and between hsCRP level and motor cortex FC and morphology.</div></div><div><h3>Results</h3><div>GS function in patients was impaired compared with that in HCs (<em>t</em> = –2.635, <em>p</em> = 0.009). Moderation models showed that hsCRP level significantly aggravated PMR severity at low levels of GS function, whereas this effect was negligible in patients with optimal GS function (<em>F</em> = 6.725, <em>p</em> = 0.021). GS function also exhibited a moderation effect on inflammation-related alterations in morphology (<em>F</em> = 13.86, <em>p</em> = 0.047) and FC (<em>F</em> = 13.765, <em>p</em> &lt; 0.001) in the motor circuit.</div></div><div><h3>Conclusion</h3><div>A well-functioning GS mitigates inflammation-induced PMR and protects neurons from inflammatory damage. Given its moderating effect, GS function may play a crucial role in MDD psychopathology, and targeting GS function may have therapeutic value as an MDD treatment strategy.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 387-395"},"PeriodicalIF":8.8,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691206","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanistic insights into the neuroprotective effects of low-intensity transcranial ultrasound stimulation in post-cardiac arrest brain injury: Modulation of the Piezo1-Dkk3/PI3K-Akt pathway","authors":"Shuang Xu ,&nbsp;Lulu Gu ,&nbsp;Banghe Bao ,&nbsp;Qian Liu ,&nbsp;Qiaofeng Jin ,&nbsp;Yannan Ma ,&nbsp;Siyi Zhou ,&nbsp;Beibei Li ,&nbsp;Li Xu ,&nbsp;Guangqi Guo ,&nbsp;Jinpiao Zhu ,&nbsp;Kuan-Pin Su ,&nbsp;Peng Sun","doi":"10.1016/j.bbi.2025.03.027","DOIUrl":"10.1016/j.bbi.2025.03.027","url":null,"abstract":"<div><div>Post-cardiac arrest brain injury (PCABI) remains a significant challenge, marked by high mortality and disability rates due to persistent neuroinflammation. This study explored the neuroprotective potential of low-intensity transcranial ultrasound stimulation (LITUS) in mitigating brain damage after cardiopulmonary resuscitation (CPR) using a murine model and in vitro assays. LITUS treatment improved 24-h survival rates and neurological recovery in cardiac arrest (CA) mice, as evidenced by behavioral assessments and reduced neurological deficit scores. Proteomic analyses revealed modulation of Piezo1-Dkk3/PI3K-Akt signaling pathway, characterized by decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Mechanistic studies demonstrated that LITUS enhanced Piezo1 and Dkk3 activation, promoting calcium influx and anti-inflammatory responses. The Piezo1 antagonist GsMTx4 abrogated these effects, underscoring Piezo1’s specific role. Additionally, in vitro experiments using oxygen/glucose deprivation and reoxygenation (OGD/R)-treated BV2 microglial cells confirmed that LITUS reduced inflammatory responses and enhanced cellular recovery via the Piezo1-Dkk3 axis. These findings highlight LITUS as a promising non-invasive therapeutic strategy to ameliorate PCABI by modulating neuroinflammation through the Piezo1-Dkk3/PI3K-Akt pathway. This work provides a basis for translational research and potential clinical applications in improving outcomes for CPR survivors.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 341-357"},"PeriodicalIF":8.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673251","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale effects of prenatal inflammation and early life circadian disruption in mice: Implications for neurodevelopmental disorders","authors":"Tara C. Delorme ,&nbsp;Danusa M. Arcego ,&nbsp;Danae Penichet ,&nbsp;Nicholas O’Toole ,&nbsp;Nikki Huebener ,&nbsp;Patrícia P. Silveira ,&nbsp;Lalit K. Srivastava ,&nbsp;Nicolas Cermakian","doi":"10.1016/j.bbi.2025.03.023","DOIUrl":"10.1016/j.bbi.2025.03.023","url":null,"abstract":"<div><div>Around 80 % of individuals with neurodevelopmental disorders such as schizophrenia and autism spectrum disorders experience disruptions in sleep/circadian rhythms. We explored whether environmental circadian disruption interacts with prenatal infection, a risk factor for neurodevelopmental disorders, to induce sex-specific deficits in mice. A maternal immune activation (MIA) protocol was used by injecting pregnant mice with viral mimic poly IC or saline at E9.5. Juvenile/adolescent male and female offspring (3–7 weeks old) were then subjected to a standard light:dark cycle (12:12LD) or to constant light (LL). Significant interactions between treatment (MIA, control) and lighting (12:12LD, LL) were evident in behaviors related to cognition, anxiety, and sociability. This pattern persisted in our RNA sequencing analysis of the dorsal hippocampus, where poly IC exposure resulted in numerous differentially expressed genes (DEGs) in males, while exposure to both poly IC and LL led to a marked reduction in DEGs. Through WGCNA analysis, many significant gene modules were found to be positively associated with poly IC (vs. saline) and LL (vs. LD) in males (fewer in females). Many of the identified hub-bottleneck genes were homologous to human genes associated with sleep/circadian rhythms and neurodevelopmental disorders as revealed by GWA studies. The MIA- and LL-associated modules were enriched in microglia gene signatures, which was paralleled by trends of effects of each of the factors on microglia morphology. In conclusion, in a mouse model of prenatal infection, circadian disruption induced by LL during adolescence acts as a modulator of the effects of MIA at behavioral, cellular, and molecular levels.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 409-422"},"PeriodicalIF":8.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143673248","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}

{"title":"The schizophrenia-associated gene CSMD1 encodes a complement classical pathway inhibitor predominantly expressed by astrocytes and at synapses in mice and humans","authors":"Robert A.J. Byrne ,&nbsp;Jacqui Nimmo ,&nbsp;Megan Torvell ,&nbsp;Sarah M. Carpanini ,&nbsp;Nikoleta Daskoulidou ,&nbsp;Timothy R. Hughes ,&nbsp;Lucy V. Noble ,&nbsp;Aurora Veteleanu ,&nbsp;Lewis M. Watkins ,&nbsp;Wioleta M. Zelek ,&nbsp;Michael C. O’Donovan ,&nbsp;Bryan Paul Morgan","doi":"10.1016/j.bbi.2025.03.026","DOIUrl":"10.1016/j.bbi.2025.03.026","url":null,"abstract":"<div><div>CUB and sushi multiple domains 1 (<em>CSMD1</em>) is predominantly expressed in brain and robustly associated with schizophrenia risk; however, understanding of which cells express CSMD1 in brain and how it impacts risk is lacking. <em>CSMD1</em> encodes a large transmembrane protein including fifteen tandem short consensus repeats (SCRs), resembling complement C3 convertase regulators. CSMD1 complement regulatory activity has been reported and mapped to SCR17-21. We expressed two SCR domains of CSMD1, SCR17-21 and SCR23-26, and characterised their complement regulatory activity using a panel of functional assays testing convertase and terminal pathway inhibition. Both domains inhibited the classical pathway C3 convertase by acting as factor I cofactors; neither domain caused any inhibition in alternative or terminal pathway assays. Novel anti-CSMD1 monoclonal antibodies cross-reactive with human and mouse CSMD1 were generated that detected endogenous CSMD1 in human and rodent brain; immunostaining showed predominantly astrocyte and synaptic localisation of CSMD1, the latter confirmed using isolated synapses. Using iPSC-derived cells, astrocyte expression was confirmed and expression on cortical neurons demonstrated. We show that CSMD1 is a classical pathway-specific complement regulator expressed predominantly on astrocytes, neurons, and synapses in human and mouse brain. These findings will help reveal the mechanism by which CSMD1 impacts schizophrenia risk.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 287-302"},"PeriodicalIF":8.8,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143669001","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}

{"title":"Differences in inflammation among black and white individuals: A systematic review and meta-analysis","authors":"Cameron R. Wiley ,&nbsp;DeWayne P. Williams ,&nbsp;Christine Sigrist ,&nbsp;Briana N. Brownlow ,&nbsp;Anna Markser ,&nbsp;Suzi Hong ,&nbsp;Esther M. Sternberg ,&nbsp;Gaston Kapuku ,&nbsp;Julian Koenig ,&nbsp;Julian F. Thayer","doi":"10.1016/j.bbi.2025.03.019","DOIUrl":"10.1016/j.bbi.2025.03.019","url":null,"abstract":"<div><h3>Importance</h3><div>Despite persisting health disparities between Black and White individuals, racial differences in inflammation have yet to be comprehensively examined.</div></div><div><h3>Objective</h3><div>To determine if significant differences in circulating levels of inflammatory markers between Black and White populations exist.</div></div><div><h3>Data sources</h3><div>Studies were identified through systematic searches of four electronic databases in January 2022. Additional studies were identified via reference lists and e-mail contact.</div></div><div><h3>Study selection</h3><div>Eligible studies included full-text empirical articles that consisted of Black and White individuals and reported statistics for inflammatory markers for each racial group. Of the 1368 potentially eligible studies, 84 (6.6 %) representing more than one million participants met study selection criteria.</div></div><div><h3>Data extraction and synthesis</h3><div>Risk of bias was assessed via meta regressions that considered relevant covariates. Data heterogeneity was tested using both the Cochrane Q-statistic and the standard <em>I²</em> index. Random effects models were used to calculate estimates of effect size from standardized mean differences.</div></div><div><h3>Main outcomes and measures</h3><div>Outcome measures included 12 inflammatory markers, including C-reactive protein (CRP), Fibrinogen, Interleukin-6 (IL-6), Tumor necrosis factor-alpha (TNF-α), and soluble intercellular adhesion molecule 1 (sICAM-1).</div></div><div><h3>Results</h3><div>Several markers had robust sample sizes for analysis, including CRP (White <em>N</em> = 934,594; Black <em>N</em> = 55,234), Fibrinogen (White <em>N</em> = 80,880; Black <em>N</em> = 18,001), and IL-6 (White <em>N</em> = 20,269; Black <em>N</em> = 14,675). Initial results indicated significant effects on CRP (<em>k</em> = 56, pooled Hedges’ <em>g</em> = 0.24), IL-6 (<em>k</em> = 33, <em>g</em> = 0.15), and Fibrinogen (<em>k</em> = 19, <em>g</em> = 0.49), with Black individuals showing higher levels. Results also indicated significant effects on sICAM-1 (<em>k</em> = 6, <em>g</em> = −0.46), and Interleukin-10 (<em>k</em> = 4, <em>g</em> = −0.18), with White individuals showing higher levels. Sensitivity analyses confirmed robust effects for CRP, IL-6, Fibrinogen, and sICAM-1 while also revealing significant effects on TNF-α (<em>k</em> = 18, <em>g</em> = −0.17) and Interleukin-8 (<em>k</em> = 5, <em>g</em> = −0.19), with White individuals showing higher levels of both.</div></div><div><h3>Conclusions and relevance</h3><div>Current <em>meta</em>-analytic results provide evidence for marked racial differences in common circulating inflammatory markers and illustrate the complexity of the inflammatory profile differences between Black and White individuals.</div><div><strong>Review Pre-Registration:</strong> PROSPERO Identifier – CRD42022312352.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 269-286"},"PeriodicalIF":8.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656143","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Astrocyte elevated gene-1 (AEG-1) in myeloid cells is a key driver for the development of chemotherapy-induced peripheral neuropathy","authors":"Bryan D. Mckiver ,&nbsp;Sara M. Herz ,&nbsp;Shivani Patel ,&nbsp;Tayla Bryan ,&nbsp;Jared Mann ,&nbsp;Justin L. Poklis ,&nbsp;John W. Bigbee ,&nbsp;Jolene J. Windle ,&nbsp;Aliasger K. Salem ,&nbsp;Devanand Sarkar ,&nbsp;M.Imad Damaj","doi":"10.1016/j.bbi.2025.03.020","DOIUrl":"10.1016/j.bbi.2025.03.020","url":null,"abstract":"<div><div>Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting side effect of chemotherapy treatment, often resulting in the discontinuation of treatment. Paclitaxel activates peripheral macrophages, generating a neuroinflammatory response that contributes to CIPN development and maintenance.</div><div>Astrocyte Elevated Gene-1 (AEG-1), also known as Metadherin or LYRIC, is a multifunctional protein that modulates macrophage activity and regulates inflammation through direct interaction with NF-κB, a transcriptional regulator of proinflammatory cytokine/chemokine (PIC) expression.</div><div>We aimed to determine whether AEG-1 contributes to the development and maintenance of CIPN pathologies by using both global (AEG-1 KO) and myelocyte-specific knockout (AEG-1ΔMAC) transgenic mouse strains in an animal model of CIPN that replicates specific human clinical phenotypes. We hypothesized that inhibition of AEG1 expression in myeloid cells, such as monocytes and macrophages, would prevent the development and maintenance of CIPN.</div><div>Our results showed that global AEG-1 deletion prevented the development of CIPN pathologies induced by PAC, as well as oxaliplatin (OHP). PAC treatment was found to increase AEG-1 and PIC expression in the DRGs of WT mice and in peritoneal macrophages isolated from C57BL/6J mice. However, in the absence of AEG-1 expression, PAC-induced neuroinflammation was completely halted in the DRGs of AEG-1 KO mice. This preventative phenotype and PIC expression profile was mirrored in AEG-1ΔMAC mice, which also displayed reduced NF-κB protein levels and F4/80+ macrophages trafficked to the lumbar DRGs following PAC treatment.</div><div>In summary, our results are the first to demonstrate the biological role AEG-1, particularly in myeloid cells, in development of CIPN.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"127 ","pages":"Pages 329-340"},"PeriodicalIF":8.8,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656141","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}