Brain, Behavior, and Immunity最新文献

{"title":"Chronic intermittent hypoxia drives M1 macrophage polarization in dorsal root ganglia","authors":"Samuel B. Chivers ,&nbsp;Mary Ann Andrade ,&nbsp;Cassandra L. McLay ,&nbsp;Kristopher L. Wieland ,&nbsp;Pankil K. Shah ,&nbsp;Glenn M. Toney ,&nbsp;Nathaniel A. Jeske","doi":"10.1016/j.bbi.2025.06.028","DOIUrl":"10.1016/j.bbi.2025.06.028","url":null,"abstract":"<div><div>Immune cells play a crucial role in maintaining the health of all body tissues. When chemical signals are released into the local environment from injured or infected cells, tissue-specific immune cells become attracted and migrate to that area. Upon arrival, they begin releasing their own signals that produce a cascade of effects, including pain modulation. However, little is known about how systemic hypoxia influences immune modulation of pain in the peripheral nervous system. We sought to identify the unique role of macrophages in peripheral sensory ganglia by using a translational model of sleep apnea. Mice were exposed to chronic intermittent hypoxia (CIH) for 14 days and L4-L6 dorsal root ganglia were removed for analyses of macrophage content. Immunofluorescence histochemistry and fluorescence-activated cell sorting indicate a prevalence of M1 macrophage markers and a reduction of M2 macrophage markers in DRG tissues taken from CIH mice. Total RNA-seq identified multiple genes upregulated in DRG macrophages following CIH exposure, including toll-like receptor 9 (TLR9). In vitro treatment of primary macrophage cultures with the FDA-approved TLR9 antagonist hydroxychloroquine (HCQ) inhibited M1 macrophage polarization. Calcium imaging of DRG neurons taken from CIH-exposed mice revealed hypersensitivity to KCL that was prevented by HCQ co-treatment. Furthermore, HCQ acutely abated hyperalgesic priming behavior in mice exposed to CIH. Together, these results identify TLR9 as a druggable target capable of reducing nociceptor sensitization in CIH, with implications for exaggerated pain sensitivity in patients with sleep apnea.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 442-452"},"PeriodicalIF":8.8,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365216","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":"Identification of SAA1 in extracellular vesicles contribute to methamphetamine withdrawal","authors":"Yehong Fang ,&nbsp;Yanpan Gao ,&nbsp;Feiyan Shen ,&nbsp;Ying Zhu ,&nbsp;Liangliang Wang ,&nbsp;Zuxin Chen ,&nbsp;Jinsong Tang ,&nbsp;Yanhui Liao","doi":"10.1016/j.bbi.2025.06.029","DOIUrl":"10.1016/j.bbi.2025.06.029","url":null,"abstract":"<div><div>Anxiety and depression-like symptoms are highly prevalent among methamphetamine (MA) users, particularly during the acute withdrawal (AW) phase, which plays a crucial role in the high relapse rates observed in this population. Despite their clinical importance, the mechanisms driving these withdrawal symptoms remain largely unclear. In this study, we focused on the plasma extracellular vesicles (EVs) in the MA users during the acute withdrawal (MA-AW EVs). Our findings demonstrate that the transplantation of MA-AW EVs induces anxiety and depression-like behaviors in mice, suggesting a direct link between EVs and affective withdrawal symptoms. <em>In vivo</em> and <em>in vitro</em> analyses further revealed that transplantation of MA-AW EVs induces alterations in neuronal and synaptic morphology, with withdrawal-related behaviors manifesting in a microglia-dependent manner. Proteomic profiling revealed that the EVs contained serum amyloid A-1 (SAA1) and serum amyloid A-2 (SAA2) proteins closely linked to the duration of MA withdrawal. These proteins were notably upregulated during the AW phase and declined rapidly during the protracted withdrawal (PW) stage. Subsequent experiments further validated the critical role of SAA1 in mediating anxiety and depression-like behaviors, neurotoxicity, synaptic plasticity and microgliosis. Our findings underscore the pivotal role of EVs in the MA process and suggest a close relationship between SAA1 protein and withdrawal symptoms, which may potentially serve as a novel target for MA addiction intervention.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 453-469"},"PeriodicalIF":8.8,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339835","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":"Corrigendum to \"SOAT1 dysregulation in astrocytes drives Blood-Brain barrier dysfunction and neuroinflammation in Alzheimer's disease\" [Brain Behav. Immun. 128 (2025) 497-End 509].","authors":"Lian Huang, Fu Zeng, Hui Wei, Tong Su, Yuwen Su, Yarong Lin, Qi Niu, Qi Xu","doi":"10.1016/j.bbi.2025.06.008","DOIUrl":"10.1016/j.bbi.2025.06.008","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144332451","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":"Sex differences in neurological disorders: Insights from ischemic stroke, Parkinson’s disease, and multiple sclerosis","authors":"Cassandra J. Kaufhold,&nbsp;Kathiresh Kumar Mani,&nbsp;Zara Akbari,&nbsp;Farida Sohrabji","doi":"10.1016/j.bbi.2025.06.026","DOIUrl":"10.1016/j.bbi.2025.06.026","url":null,"abstract":"<div><div>Ischemic stroke, Parkinson’s disease (PD), and multiple sclerosis (MS), are neurodegenerative disorders that exhibit significant sex differences in pathophysiology, clinical manifestations, and outcomes. Women are more likely to experience strokes in older age, with estrogen playing dual protective/detrimental roles depending on reproductive age. In PD, men show earlier onset and steadier decline, while women exhibit a protective estrogen-driven advantage and distinct gut-brain axis interactions. MS disproportionately affects women (3:1 ratio), particularly during reproductive years, with sex hormones and X-linked genes modulating autoimmune demyelination. This review synthesizes sex-specific mechanisms across these diseases, emphasizing immune dysregulation, hormonal influences, and emerging roles of the gut microbiome. Key modifiers such as epigenetic factors, microbiome composition, and sex chromosome interactions are discussed to inform personalized therapeutic strategies.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 335-347"},"PeriodicalIF":8.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144313289","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":"TNFR1 and TNFR2 levels in patients with severe alcohol use disorder undergoing withdrawal and their relationship with delirium tremens","authors":"Shu-Hao Hsu ,&nbsp;Ming-Chyi Huang ,&nbsp;Tung‑Hsia Liu ,&nbsp;Hu-Ming Chang ,&nbsp;Shu-Wei Liu ,&nbsp;Yu‑Li Liu","doi":"10.1016/j.bbi.2025.06.024","DOIUrl":"10.1016/j.bbi.2025.06.024","url":null,"abstract":"<div><h3>Background</h3><div>Chronic alcohol consumption has been associated with cytokine dysregulation. Tumor necrosis factor-alpha (TNF-α), mediated through two distinct receptors—TNF receptor type 1 (TNFR1) and TNF receptor type 2 (TNFR2)—plays a role in alcohol use disorder (AUD). Evidence also suggests a potential role of TNFR1 and TNFR2 in delirium development. We aimed to investigate the role of TNFR1 and TNFR2 in patients with AUD undergoing withdrawal and the differences in these levels between those with and without delirium tremens (DT).</div></div><div><h3>Methods</h3><div>Ninety treatment-seeking patients with severe AUD and 117 healthy controls (HC) were enrolled and measured for blood levels of TNF-α, TNFR1 and TNFR2 using enzyme-linked immunosorbent assays. We followed the levels in AUD group after 2 weeks of withdrawal and categorized them based on the occurrence of DT (DT group, n = 19) and non-DT group (n = 71) during this period.</div></div><div><h3>Results</h3><div>At both week 0 and week 2, patients with AUD had higher plasma TNFR1, TNFR2, and TNF-α levels than healthy controls, with the DT subgroup showing greater elevations than the non-DT subgroup. Although levels declined after two weeks of alcohol withdrawal, they remained elevated compared to controls. Regression analysis indicated that age, sex, and TNF-α levels were significant contributors to TNFR1 and TNFR2 levels.</div></div><div><h3>Conclusions</h3><div>This study is the first to indicate that TNFR1 and TNFR2 levels were increased in patients with AUD but decreased, though not normalized, after early abstinence. DT subgroup is associated with more severe TNFR1 and TNFR2 dysregulation than non-DT subgroup.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 409-415"},"PeriodicalIF":8.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144365657","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":"Cortical thickness and low-grade inflammation moderate the association between depressive symptoms and cognitive function in early widowhood: A preliminary study","authors":"E. Lydia Wu-Chung ,&nbsp;Kristen M. Kennedy ,&nbsp;Luis D. Medina ,&nbsp;Paul E. Schulz ,&nbsp;Frederick L. Oswald ,&nbsp;Cobi J. Heijnen ,&nbsp;Stephanie L. Leal ,&nbsp;Bryan T. Denny ,&nbsp;Christopher P. Fagundes","doi":"10.1016/j.bbi.2025.06.027","DOIUrl":"10.1016/j.bbi.2025.06.027","url":null,"abstract":"<div><div>Spousal bereavement is a major life stressor that significantly increases the risk of dementia. However, it remains unclear how the bereavement experience accelerates cognitive aging. In the broader neurocognitive aging literature, depression and cognitive function are closely linked, such that depression is sometimes accompanied by cognitive impairments. Individual differences in depression-related cognitive function may depend on low-grade inflammation and cortical atrophy, two phenomena implicated in cognitive dysfunction and dementia risk. No study to date has examined how psychobiological health relates to cognition in early widowhood. Among recently bereaved spouses, we examined (1) whether depressive symptom severity accounted for variations in cognitive performance and (2) whether the association between depressive symptoms and cognitive function depended on one’s biological profile. In a sample of 68 bereaved spouses, depressive symptom severity, cortical thickness in 8 <em>a priori</em> regions, serum proinflammatory composite (IL-6, sIL-6R, TNF-⍺, sTNFRI, and sTNFRII), and a battery of cognitive tests were evaluated at 6 months post-loss. Using multiple linear regression to test hypotheses, we observed a significant negative association between depressive symptoms and performance on global cognitive function, cognitive inhibition, visuospatial processing, and working memory. The interaction between depressive symptoms and the cortical signature composite on global cognition was statistically significant: Depressive symptoms were negatively associated with global cognitive function, only for widow(er)s with average and less than average cortical gray matter. The interaction between depressive symptoms and low-grade inflammation on cognitive inhibition was also statistically significant: Depressive symptoms were negatively associated with cognitive inhibition only for those with average and higher than average levels of the serum inflammatory composite. This suggests that widow(er)s experiencing higher levels of depressive symptoms were more likely to have poorer cognitive function, especially if they presented with a more adverse biological profile (i.e., higher cytokine levels and less cortical gray matter than average); in contrast, for widow(er)s with less adverse biological profiles, there was no evidence for an association between depressive symptoms and cognitive function. This exploratory study identifies psychobiological correlates of cognitive function in early widowhood, offering insight into risk factors for abnormal cognitive aging after profound interpersonal loss.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 620-633"},"PeriodicalIF":8.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144336328","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":"Corrigendum to \"Early-life gut inflammation drives sex-dependent shifts in the microbiome-endocrine-brain axis\" [Brain Behav. Immun. 125 (2025) 117-139].","authors":"Olivia Sullivan, Claire Sie, Katharine M Ng, Sophie Cotton, Cal Rosete, Jordan E Hamden, Ajay Paul Singh, Kristen Lee, Jatin Choudhary, Jennifer Kim, Huaxu Yu, Charlotte A Clayton, Natalia A Carranza Garcia, Kateryna Voznyuk, Brian D Deng, Nadine Plett, Sana Arora, Hans Ghezzi, Tao Huan, Kiran K Soma, John-Paul J Yu, Carolina Tropini, Annie Vogel Ciernia","doi":"10.1016/j.bbi.2025.06.007","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.06.007","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324524","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":"Corrigendum to \"Microbiota-microglia crosstalk between Blautia producta and neuroinflammation of Parkinson's disease: A bench-to-bedside translational approach\" [Brain, Behavior, and Immunity 117 (2024) 270-282].","authors":"Jiaming Liu, Xinhuang Lv, Tao Ye, Ming Zhao, Zhibo Chen, Yang Zhang, Wenwen Yang, Huijia Xie, Lu Zhan, Liuzhu Chen, Wen-Chun Liu, Kuan-Pin Su, Jing Sun","doi":"10.1016/j.bbi.2025.06.006","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.06.006","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"PeriodicalIF":8.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144324525","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":"Latent classes of adverse childhood experiences and changes in inflammation across middle age among urban-dwelling adults","authors":"Eileen M. Condon ,&nbsp;Ana I. Maldonado ,&nbsp;Michele K. Evans ,&nbsp;Alan B. Zonderman","doi":"10.1016/j.bbi.2025.06.018","DOIUrl":"10.1016/j.bbi.2025.06.018","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 494-504"},"PeriodicalIF":8.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144483149","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":"Protective impact of physical exercise on methamphetamine-induced neuroinflammation and neurogenesis impairment depends on the activity level","authors":"Mateusz Smolarz ,&nbsp;Magdalena Dębiec ,&nbsp;Gracjana Zając ,&nbsp;Natalia Pondel ,&nbsp;Katarzyna Bogus ,&nbsp;Agnieszka Kosowska ,&nbsp;Ewelina Pieprzyca ,&nbsp;Bogusława Orzechowska-Wylęgała ,&nbsp;Andrzej Małecki ,&nbsp;Marta Nowacka-Chmielewska ,&nbsp;Michal Toborek","doi":"10.1016/j.bbi.2025.06.025","DOIUrl":"10.1016/j.bbi.2025.06.025","url":null,"abstract":"<div><div>One of the outcomes of methamphetamine (METH) misuse is impaired hippocampal function. In addition, regular physical exercise has been proposed as an effective behavioral intervention with numerous health benefits, particularly in the treatment of drug misuse. In this study, we evaluated the impact of physical exercise on METH-induced neurotoxicity and inflammation in male and female adult mice. Importantly, we assessed whether the protective effects of exercise vary depending on activity levels. Our findings indicate that METH causes neuroinflammation, abnormal neurogenesis, and cognitive impairment in mice, with notable sexual dimorphism in response to METH toxicity. In addition, the protective effect of physical exercise against METH-induced neuroinflammation and neurogenesis impairment depended on the activity level. Overall, our results indicate the importance of introducing tailored physical exercise protocols into treatment and recovery strategies for individuals who misuse psychoactive substances, such as METH.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"129 ","pages":"Pages 373-387"},"PeriodicalIF":8.8,"publicationDate":"2025-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144330440","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}