Brain, Behavior, and Immunity最新文献

{"title":"Dr. Linda R. Watkins: A pioneer who rewrote the science of pain and neuroimmune signaling","authors":"Mark R. Hutchinson ,&nbsp;Erin D. Milligan ,&nbsp;Peter M. Grace","doi":"10.1016/j.bbi.2025.05.013","DOIUrl":"10.1016/j.bbi.2025.05.013","url":null,"abstract":"<div><div>Dr. Linda R. Watkins, a Distinguished Professor at the University of Colorado Boulder, fundamentally altered the understanding of pain and neuroimmune signaling. As she concludes her tenure as Associate Editor of Brain, Behavior, and Immunity, this tribute reflects<!--> <!-->on her revolutionary discoveries. She pioneered the concept that glial cells actively participate in pain states, challenging neuron-centric dogma. Her work elucidated the roles of cytokines like IL-1β and IL-10, the chemokine fractalkine (CX3CL1), and the Toll-Like Receptor 4 (TLR4) in glial reactivity, sickness behavior, and unwanted opioid effects (tolerance, hyperalgesia). As a dedicated mentor and collaborator, particularly with Steve Maier, she fosters interdisciplinary research. Watkins champions translational science, co-founding Xalud Therapeutics to develop immune therapies like IL-10 gene therapy, leaving a profound legacy in neuroscience.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 685-688"},"PeriodicalIF":8.8,"publicationDate":"2025-05-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070635","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":"Blood immuno-metabolic biomarker signatures of depression and affective symptoms in young adults","authors":"Nicholas A. Donnelly ,&nbsp;Ruby S.M. Tsang ,&nbsp;Éimear M. Foley ,&nbsp;Holly Fraser ,&nbsp;Aimee L. Hanson ,&nbsp;Golam M. Khandaker","doi":"10.1016/j.bbi.2025.05.011","DOIUrl":"10.1016/j.bbi.2025.05.011","url":null,"abstract":"<div><h3>Background</h3><div>Depression is associated with alterations in immuno-metabolic biomarkers, but it remains unclear whether these alterations are limited to specific markers, and whether there are subtypes of depression and depressive symptoms which are associated with specific patterns of immuno-metabolic dysfunction.</div></div><div><h3>Methods</h3><div>To investigate whether immuno-metabolic biomarkers could be used to profile subtypes of depression, we applied regression, clustering, and machine learning to a dataset comprising depression diagnosis, depressive and anxiety symptoms, and blood-based immunological and metabolic biomarkers (n = 118). We measured inflammatory proteins, cell counts, lipids, hormones, and metabolites from up to n = 4161 participants (2363 female, 337 with depression) aged 24 years from the Avon Longitudinal Study of Parents and Children birth cohort.</div></div><div><h3>Results</h3><div>Depression at age 24 was associated with both altered concentrations of immuno-metabolic markers, and increased extreme-valued inflammatory markers. Inflammatory and metabolic biomarkers show distinct, opposing associations with somatic and anxiety symptoms. We identified two latent components representing the relationship between blood biomarkers, symptoms, and covariates, one characterised by higher somatic symptoms and inflammatory markers (neutrophils, WBC, IL-6), and the other characterised by higher anxiety and worry and lower inflammatory markers (CRP, WBC, IL-6). Individuals with higher somatic-inflammatory component scores had greater depressive symptoms severity over the next five years. Immuno-metabolic biomarkers predicted depression diagnosis (Balanced Accuracy = 0.580) and depression with high somatic symptoms (Balanced Accuracy = 0.575) better than chance, but not depression with high anxiety symptoms (Balanced Accuracy = 0.479).</div></div><div><h3>Conclusions</h3><div>Alterations in immuno-metabolic homeostasis is present in young adults with depression well before the typical age of onset of cardiometabolic diseases. The relationships between affective symptoms and blood immuno-metabolic biomarkers indicate two biotypes of depressive symptoms (somatic-inflamed vs anxious-non-inflamed). These patterns are relevant for prognosis and prediction, highlighting the potential usefulness of immuno-metabolic biomarkers for depression subtyping.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 673-684"},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144070634","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":"Using a murine model to explore the impact of sex and APOE4 on cisplatin-induced cognitive impairment.","authors":"Caroline G Fowler, Mia I Tarantino, Avery E Gillett, Valeria Muñiz, Marlee A Anderson, Reece L Bonner, Elisabeth G Vichaya","doi":"10.1016/j.bbi.2025.05.010","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.05.010","url":null,"abstract":"<p><p>Chemotherapy-induced cognitive impairment (CICI) is reported in over 35 % of cancer survivors. Understanding risk factors for the development of CICI may provide insight into mechanisms and treatment. Being female and carrying the E4 allele of the APOE gene are risk factors for late-onset Alzheimer's disease, and there is emerging evidence that they may also confer risk for CICI. We sought to investigate these factors in a middle-aged (8-9 months) murine model of CICI. We used a 2 (+/- cisplatin) x 2 (male/female) x 2 (wild-type/APOE4 transgenic) factorial design in which cisplatin, or an equal volume of saline vehicle, was administered at 2.3 mg/kg/day for 5 days for 2 rounds separated by a 5-day rest. Behavioral tests of cognition and activity were evaluated one month after treatment completion followed by tissue collection. Male mice exhibited more severe weight loss following cisplatin irrespective of genotype. Cisplatin was also associated with reduced open-field and nest building activity for both sexes and genotypes. In the puzzle box task, cisplatin treatment reduced performance in the task with indication that sex and genotype trial dependently modulated performance. In the novel object task male mice of both genotypes showed cisplatin-induced deficits. In analyzing tissue, we did not note significant cisplatin-induced neuroinflammatory processes. We did observe an effect of cisplatin on brain Bdnf mRNA expression that varied by brain region, sex, and genotype. Within the hippocampus, cisplatin reduced Bdnf in male mice but mildly elevated it within female mice; within the frontal cortex, Bdnf expression was reduced by cisplatin in both sexes but more severely in APOE4 mice. Overall, our data provide evidence that both sex and genotype may modulate the effect of cisplatin on the brain and on cognitive performance.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075825","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":"Dysfunction of cholinergic neuron in nucleus ambiguous aggravates sepsis-induced lung injury via a GluA1-dependment mechanism","authors":"Junli Jiang ,&nbsp;Shiqing Ai ,&nbsp;Chengdong Yuan ,&nbsp;Qianjin Wang ,&nbsp;Bo Xu ,&nbsp;Liang Zhou ,&nbsp;Lin Zhang ,&nbsp;Yi Chen ,&nbsp;Tian Yu ,&nbsp;Haiying Wang","doi":"10.1016/j.bbi.2025.05.006","DOIUrl":"10.1016/j.bbi.2025.05.006","url":null,"abstract":"<div><div>Clinical and neuropathological observations suggest that patients with sepsis may have brainstem autonomic dysfunction. However, the influence of peripheral inflammation on vagal preganglionic neurons is poorly understood. Our hypothesis is that sepsis-induced central vagus dysfunction affects the cholinergic anti-inflammatory pathway and consequently contributes to respiratory failure. Here, we identified neuron apoptosis in the nucleus ambiguus (NA) after sepsis; NA is not only a component of the efferent arm of the inflammatory reflex but also plays an important role in respiratory regulation. Conditional ablation of cholinergic neurons in the NA leads to a decrease in vagus nerve firing, significant impairment of respiratory function, and inflammatory changes in lung tissues. The accumulation of glutamate and increased expression of Ca²⁺-permeable (CP)-AMPA receptors (AMPARs) mediated the excitotoxicity of NA neurons. Microinjection of IEM1460 (a selective blocker of GluA2- lacking AMPARs) partly rescued vagus firing and respiratory function in mice with sepsis. We showed that peripheral sepsis caused brainstem inflammation and impaired the cholinergic anti-inflammatory pathway after infection. We conclude that central efferent vagus dysfunction may impact vital organ systems in sepsis.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 689-702"},"PeriodicalIF":8.8,"publicationDate":"2025-05-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965795","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":"Brain inflammation and its predictive value for post-operative pain in total knee arthroplasty patients","authors":"Zeynab Alshelh ,&nbsp;Ludovica Brusaferri ,&nbsp;Erin Janas Morrissey ,&nbsp;Angel Torrado-Carvajal ,&nbsp;Minhae Kim ,&nbsp;Oluwaseun Akeju ,&nbsp;Grace Grmek ,&nbsp;Courtney Chane ,&nbsp;Jennifer Murphy ,&nbsp;Andrew Schrepf ,&nbsp;Richard E. Harris ,&nbsp;Young-Min Kwon ,&nbsp;Hany Bedair ,&nbsp;John Siliski ,&nbsp;Antonia F. Chen ,&nbsp;Christopher Melnic ,&nbsp;Mohamed Jarraya ,&nbsp;Vitaly Napadow ,&nbsp;Mattia Veronese ,&nbsp;Lucia Maccioni ,&nbsp;Marco L. Loggia","doi":"10.1016/j.bbi.2025.05.008","DOIUrl":"10.1016/j.bbi.2025.05.008","url":null,"abstract":"<div><div>Recent evidence suggests that chronic pain patients exhibit elevated brain levels of the neuroinflammation marker 18 kDa translocator protein (TSPO). However, the clinical significance of brain TSPO elevations, and their responses to pain interventions, remain unknown. To explore these questions, we studied patients with knee osteoarthritis (KOA) undergoing total knee arthroplasty (TKA), a procedure which is curative for most, but carries a relatively high risk of persistent post-surgical pain. Pre-surgical KOA patients (n = 41) and healthy controls (n = 22) underwent brain positron emission tomography/magnetic resonance imaging, using the TSPO radioligand [¹¹C]PBR28. A subset of KOA patients (n = 27) returned for a second scan one-year post-TKA. When compared groups, pre-surgical KOA patients exhibited widespread [¹¹C]PBR28 PET signal elevations (Standardized Uptake Value Ratio), with pituitary uptake positively correlating with knee pain severity (rho = 0.51; p = 0.003). A voxel-wise paired <em>t</em>-test revealed that while most brain regions showed no change post-surgery, the [¹¹C]PBR28 PET signal significantly decreased in the thalamus and caudate, reaching control levels. Additionally, a Support Vector Machine model based on pre-surgical imaging, clinical, and demographic features, achieved a correlation of rho = 0.487 (p = 0.001) between the predicted and actual pain improvement. Top predictive features included [¹¹C]PBR28 uptake in the pituitary gland, cuneal cortex, amygdala and other regions. This study suggests that neuroinflammation 1) is widespread in KOA and, in some regions, 2) is linked to pain severity, 3) undergoes normalization following TKA, and 4) can predict post-surgical TKA outcomes. Understanding the neuroinflammatory mechanisms in KOA and post-surgical pain may guide targeted interventions and improve patient outcomes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 703-712"},"PeriodicalIF":8.8,"publicationDate":"2025-05-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143965447","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":"Composite lifestyle, genetic risk, blood biomarkers, and risk of suicide attempts: a prospective cohort study","authors":"Wei Hu ,&nbsp;Tian-Shu Liu ,&nbsp;Zhen-Zhen Shen,&nbsp;Ge Tian,&nbsp;Jia-Ning Wang,&nbsp;Zhen-Yu Zhao,&nbsp;Bao-Peng Liu,&nbsp;Cun-Xian Jia","doi":"10.1016/j.bbi.2025.05.005","DOIUrl":"10.1016/j.bbi.2025.05.005","url":null,"abstract":"<div><h3>Background</h3><div>Although individual lifestyle factors may be associated with suicide attempts (SA), the prospective association of composite lifestyles with SA remains unknown. Furthermore, whether this association is modulated by genetic risk remains to be elucidated. The study aimed to investigate the association of composite lifestyles and genetic risk with SA risk and to explore the underlying biological mechanisms.</div></div><div><h3>Methods</h3><div>435,154 individuals from the UK Biobank without a history of SA at baseline were enrolled. The SA diagnosis was based on the International Classification of Diseases coding system. Composite lifestyles were developed based on seven modifiable lifestyle factors and categorized into favorable, intermediate, and unfavorable groups. According to the polygenic risk score for SA, genetic risk was classified as low, intermediate, or high. Cox proportional hazard models and mediation analyses were conducted to examine the associations and mechanisms, respectively.</div></div><div><h3>Findings</h3><div>During a mean follow-up of 13.6 years, 1,515 (0.35 %) individuals experienced SA. Compared to individuals with favorable lifestyles, the HR (95 % CI) for SA among those with unfavorable lifestyles was 2.19 (1.93–2.48). The risk of SA was 68 % higher among those with high genetic risk compared with low-risk individuals (HR = 1.68, 95 % CI: 1.48–1.92). The joint test revealed that individuals with unfavorable lifestyles and high genetic risk faced the highest risk of SA (HR = 3.58, 95 % CI: 2.91–4.40), which could be explained by an additive interaction. Several biomarkers in liver function, endocrine, inflammation, and blood cell pathways collectively explained 15.84 % (95 % CI: 7.68 %-27.68 %) of the association.</div></div><div><h3>Interpretation</h3><div>Adherence to favorable lifestyles was associated with a lower risk of SA, especially among those at high genetic risk. The beneficial association might be partially explained by improvement in key mediating biomarkers.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 634-642"},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143942073","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":"Pretreatment with dimethyl fumarate prevents chronic pain and its comorbidities via Nrf2 pathway in a rat model of neuropathic pain.","authors":"Anh Cong Tuan Le, Juliana Fiuza-Fernandes, Joana Margarida Silva, Mariana Teixeira Sampaio, Andreia Texeira-Castro, Sara Duarte-Silva, Hugo Leite-Almeida","doi":"10.1016/j.bbi.2025.05.003","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.05.003","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143976011","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":"LPS-induced systemic inflammation disrupts brain activity in a region- and vigilance-state specific manner","authors":"Susan Leemburg ,&nbsp;Annu Kala ,&nbsp;Athira Nataraj,&nbsp;Patricia Karkusova,&nbsp;Siddharth Baindur,&nbsp;Amritesh Suresh,&nbsp;Karel Blahna,&nbsp;Karel Jezek","doi":"10.1016/j.bbi.2025.05.002","DOIUrl":"10.1016/j.bbi.2025.05.002","url":null,"abstract":"<div><div>Sepsis-associated encephalopathy (SAE) is a common complication of sepsis and the systemic inflammatory response syndrome that leads to lasting consequences in survivors. It manifests as early EEG changes that are region-, time- and state-specific, possibly reflecting distinct mechanisms of injury.</div><div>Here, we investigated the effects of 5 mg/kg lipopolysaccharide (LPS) on hippocampal and cortical sleep-wake states, oscillatory and non-oscillatory neuronal activity, as well as on within- and between-state dynamics using state-space analysis.</div><div>LPS induced rapid-onset severe temporal and spatial vigilance state fragmentation, which preceded all other spectral changes by ∼90 min. Thereafter, LPS led to specific destabilization and increased delta oscillatory activity in wakefulness, but not NREM sleep, although state transitions remained largely normal. Instead, reduced NREM delta power resulted from aperiodic spectrum changes. LPS specifically reduced higher frequency hippocampal gamma oscillations (60–80 Hz peak) in wakefulness, but not cortical high gamma or lower frequency gamma oscillations.</div><div>These results suggest that disruption of sleep-wake patterns could serve as an early indicator of sepsis and associated encephalopathy, independent of spectral changes. Moreover, treatment aimed at stabilizing vigilance states in early stages of sepsis might prove to be a novel option preventing the development of further pathological neurophysiology, as well as limiting inflammation-related brain damage.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 713-724"},"PeriodicalIF":8.8,"publicationDate":"2025-05-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143959536","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":"A long-term mixed eosinophilic and neutrophilic chronic rhinosinusitis C57BL/6 mouse model with neuroinflammation, olfactory dysfunction and anxiety-like behaviors","authors":"Xiaojun Zhang ,&nbsp;Wensi Wu ,&nbsp;Haomiao Zhao ,&nbsp;Changqing Li ,&nbsp;Lijie Qi ,&nbsp;Changhua Wu ,&nbsp;Xinyu Xie ,&nbsp;Binxiang Tang ,&nbsp;Pin Wang ,&nbsp;Min Jin ,&nbsp;Xin Feng","doi":"10.1016/j.bbi.2025.05.001","DOIUrl":"10.1016/j.bbi.2025.05.001","url":null,"abstract":"<div><h3>Background</h3><div>Chronic rhinosinusitis (CRS) is a heterogeneous condition characterized by persistent inflammation and high recurrence rates. The mixed granulocytic endotype, marked by increased eosinophils and neutrophils, is particularly refractory and prone to relapse.</div></div><div><h3>Objective</h3><div>This study aimed to evaluate the papain-induced mouse model for investigating the more refractory mixed granulocytic CRS endotype, characterized by elevated eosinophils and neutrophils.</div></div><div><h3>Methods</h3><div>Male C57BL/6 mice were intranasally administered papain for 11 days to induce CRS. Cytokine profiles, nasal tissue histology, olfactory bulb analysis, assessments of olfactory function, cognition, anxiety-like and depression-like behaviors were performed at 30, 60, and 90 days post-treatment.</div></div><div><h3>Results</h3><div>A long-term mixed eosinophilic and neutrophilic CRS model was successfully established, showing elevated IgE, IL-4, IL-5, IL-13, IL-33, TSLP, and TNF-α in nasal lavage fluid, alongside infiltration of eosinophils and neutrophils in both olfactory and respiratory regions. Chronic pathology included increased mast cells, goblet cells, basal cells, mucus hyperproduction, and epithelial damage, persisting up to 90 days, with partial improvement observed at the 60-day mark. Brain analysis revealed ongoing neuroinflammation, olfactory dysfunction, and anxiety-like behaviors in CRS mice, without signs of cognitive impairment or depression-like behaviors.</div></div><div><h3>Conclusions</h3><div>This study phenotypically delineated a long-term mixed eosinophilic and neutrophilic CRS mouse model, demonstrating sustained neuroinflammation, olfactory dysfunction, and anxiety-like behaviors following short-term papain exposure. These findings highlighted the role of mixed inflammation in CRS and provided a time-efficient platform for further exploration of its pathogenesis and mind-brain-body interactions.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 654-672"},"PeriodicalIF":8.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941966","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":"Pro-inflammatory macrophages contribute to developing comorbid anxiety-like behaviors through gastrointestinal vagal afferent signaling in experimental colitis mice","authors":"Chin-Hao Chen ,&nbsp;Kuan-Chieh Yu ,&nbsp;Li-Jin Hsu ,&nbsp;Wen-Tai Chiu ,&nbsp;Kuei-Sen Hsu","doi":"10.1016/j.bbi.2025.05.007","DOIUrl":"10.1016/j.bbi.2025.05.007","url":null,"abstract":"<div><div>Anxiety symptoms are commonly observed in individuals with inflammatory bowel disease (IBD), but the mechanistic link between IBD and comorbid anxiety remains incompletely understood. Our previous study revealed that vagal gut-brain signaling contributes to driving comorbid anxiety-like behaviors in dextran sulfate sodium (DSS)-induced colitis mice, but how vagus nerve senses and transmits information to the brain in response to changes in the colonic microenvironment following DSS treatment remain elusive. Here, we identify a critical contribution of pro-inflammatory CD86⁺ macrophages to activate gut-innervating vagal afferents and ultimately drive anxiety-like behaviors in DSS-treated mice. An increased number of F4/80⁺ macrophages accumulated closely with gut-innervating vagal afferent fibers following DSS treatment. Depletion of macrophages alleviated DSS-induced anxiety-like behaviors, whereas peripheral delivery of lipopolysaccharide-activated M1 macrophages promoted anxiety-like behaviors, which were prevented by bilateral vagal afferent ablation. Moreover, differential expression levels of anxiety-like behaviors were positively correlated with neuronal activity changes in the nucleus tractus solitarius, locus coeruleus, and basolateral amygdala. Finally, treatment with either anti-α4β7 integrin antagonist vedolizumab or neutralizing anti-interleukin-1β monoclonal antibody effectively alleviated DSS-induced anxiety-like behaviors. Collectively, these findings unravel a mechanism of macrophage-to-vagus nerve communication via cytokine signaling responsible for comorbid anxiety associated with experimental colitis and suggest that pro-inflammatory CD86⁺ macrophages may represent a potential therapeutic target for psychological comorbidities in patients with IBD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 620-633"},"PeriodicalIF":8.8,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143931486","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}