Brain, Behavior, and Immunity最新文献

{"title":"Maternal immune activation during gestation modulates offspring immune profiles in a nonhuman primate model","authors":"Chelsea Kelland ,&nbsp;Joseph Schauer ,&nbsp;Ana-Maria Iosif ,&nbsp;Steven Rollins ,&nbsp;Apurv Srivastav ,&nbsp;Tyler Lesh ,&nbsp;Casey Hogrefe ,&nbsp;Cynthia Schumann ,&nbsp;Cameron Carter ,&nbsp;Kimberley McAllister ,&nbsp;Melissa D. Bauman ,&nbsp;Judy Van de Water","doi":"10.1016/j.bbi.2025.106207","DOIUrl":"10.1016/j.bbi.2025.106207","url":null,"abstract":"<div><h3>Background</h3><div>Maternal Immune Activation (MIA) during pregnancy is an environmental risk factor implicated in neurodevelopmental disorders such as autism spectrum disorder and schizophrenia. While numerous studies have shown that MIA can lead to neuropathological and behavioral abnormalities in offspring, the consequences for immune system development and function are less well characterized.</div></div><div><h3>Methods</h3><div>To assess the impact of MIA on offspring immune function, we utilized samples from 24 nonhuman primate (NHP) dam-infant pairs. Pregnant dams received either saline (control) or polyinosinic: polycytidylic acid [poly(I:C)] injections in the late first trimester to induce MIA. Dam sickness behaviors and immune response were monitored. Offspring immune status was assessed longitudinally by measuring plasma cytokine, chemokine, and growth factor levels at postnatal days (PND) 30, 90, and 180. Additionally, a complete blood count, including differential leukocyte counts, was performed on blood samples collected from the offspring at PND 90 to quantify immune cell profiles.</div></div><div><h3>Results</h3><div>Poly(I:C)-induced MIA triggered immediate and sustained increases in antiviral pro-inflammatory and anti-inflammatory cytokines, as well as enhanced T-cell responses in NHP dams compared with saline controls. At PND 90, MIA-exposed offspring had higher total white blood cell counts (<em>p</em> = 0.03), monocytes (<em>p</em> = 0.01), neutrophils (<em>p</em> = 0.04), and lymphocytes (<em>p</em> = 0.048) compared to controls. Further, gestational MIA exposure modulated offspring cytokine profiles at PND 30, 90, and 180, as indicated by persistent changes in the plasma levels of several cytokines and chemokines associated with both the innate and adaptive immune responses, compared with saline control offspring.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that exposure to MIA during early gestation has a significant long-term impact on the offspring’s developing immune system. These data highlight the direct connection between maternal immune perturbation during pregnancy and immune system imprinting in offspring.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106207"},"PeriodicalIF":7.6,"publicationDate":"2025-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145676587","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":"TEMPORARY REMOVAL: Sexual minority adults exhibit greater inflammation than heterosexual adults in the context of depressive symptoms and Anxiety: Pathways to health disparities.","authors":"Lisa M Christian, Rebecca R Andridge, Juan Peng, Nithya P Kasibhatla, Thomas W McDade, Tessa Blevins, Steve W Cole, Wendy D Manning, Claire M Kamp Dush","doi":"10.1016/j.bbi.2025.106202","DOIUrl":"10.1016/j.bbi.2025.106202","url":null,"abstract":"<p><p>The publisher regrets that this article has been temporarily removed. A replacement will appear as soon as possible in which the reason for the removal of the article will be specified, or the article will be reinstated. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/policies-and-standards/article-withdrawal.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":"106202"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660406","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":"Circadian rhythms and gut microbiota Dysbiosis: emerging gut-brain axis pathways in insomnia pathophysiology and Therapeutics","authors":"Dan Zhao ,&nbsp;Bo Zou ,&nbsp;Quang Le Do ,&nbsp;Suet-Kei Wu ,&nbsp;Ying Shen ,&nbsp;Yan Yang ,&nbsp;Jing X. Kang ,&nbsp;Kuan-Pin Su ,&nbsp;Bin Wang","doi":"10.1016/j.bbi.2025.106203","DOIUrl":"10.1016/j.bbi.2025.106203","url":null,"abstract":"<div><div>Insomnia, a widespread sleep disorder, significantly impacts mental and physical health. Emerging research highlights the crucial role of gut microbiota (GM) in modulating circadian rhythms (CR), which regulate sleep-wake cycles. This review explores the interplay between GM dysbiosis, CR disruptions, and insomnia, synthesizing findings from human and animal studies. GM dysbiosis is linked to reduced microbial diversity and altered abundance of key taxa, such as short-chain fatty acid-producing bacteria, which influence clock gene expression and hormonal rhythms. CR disruption exacerbates GM imbalances, forming a feedback loop that impairs sleep regulation through both central and peripheral pathways.</div><div>We also examine the therapeutic potential of probiotics in restoring GM balance and synchronizing CR. Clinical trials suggest that specific probiotic strains improve sleep quality by modulating microbial metabolites and their downstream effects on the circadian system. However, inconsistencies in outcomes underscore the need for precision interventions. The review concludes by identifying gaps in the current literature, emphasizing the necessity of integrative approaches combining metagenomics and personalized medicine to optimize GM-targeted therapies. These insights pave the way for novel, safer, and more effective strategies to manage insomnia by addressing its biological underpinnings.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106203"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660485","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":"Diabetes-linked metabolic dysfunction relates with distinct tau phosphorylation patterns, neuroinflammation and cognitive impairment in mouse models of Alzheimer’s disease","authors":"Maria Vargas-Soria ,&nbsp;Miriam Corraliza-Gomez ,&nbsp;Carmen Infante-Garcia ,&nbsp;Alan W. Stitt ,&nbsp;Rafael Simó ,&nbsp;Monica Garcia-Alloza","doi":"10.1016/j.bbi.2025.106204","DOIUrl":"10.1016/j.bbi.2025.106204","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by amyloid-β plaques and tau neurofibrillary tangles, with tau pathology being closely linked to cognitive decline. Growing evidence suggests that metabolic dysfunction including type 1 diabetes (T1D) and type 2 diabetes (T2D), as well as prediabetes (PreDM), exacerbate AD by promoting different degrees of insulinopenia, insulin resistance and hyperglycemia which can drive chronic inflammation and oxidative stress across multiple organs. Precisely how these metabolic disturbances influence tau phosphorylation remains unclear. To address this, we studied mouse models of AD, T1D, PreDM, T2D and the combination of AD with all three metabolic alterations, at 26 weeks of age, when pathologies are well established. The fact that we are including models of insulin resistance and insulin deficiency allows us to further explore the specific role of insulin as observed in the clinic. We assessed metabolic status, tau phosphorylation and cytokine levels in the brain cortex and cognitive function using the Morris water maze (MWM) and novel object discrimination (NOD) tests. Our results revealed that AD mice with metabolic disorders exhibited tau hyperphosphorylation, particularly at Ser199, Ser202/Thr205 and Ser404, correlating with metabolic dysfunction, cognitive impairment and inflammatory markers. Notably, AD-T2D mice showed the most severe deficits in MWM and NOD performance, indicating a synergistic cognitive decline. Machine learning analysis by random forest effectively classified AD-metabolic phenotypes, identifying key molecular and metabolic markers of neurodegeneration, mainly blood glucose and plasma insulin. These findings highlight the critical role of metabolic dysfunction in exacerbating tau pathology and accelerating cognitive decline in AD. Targeting metabolic pathways may provide concomitant therapeutic opportunities for AD patients with diabetes. Future research should explore interventions that restore insulin signaling and glucose metabolism to mitigate AD progression, probably by repurposing antidiabetic drugs.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106204"},"PeriodicalIF":7.6,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145660409","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 “Gut microbiome-derived tryptophan metabolites predict relapse in alcohol use disorder”","authors":"Cameron Forton ,&nbsp;Jack DeVries ,&nbsp;Miles Lou ,&nbsp;Samuel Brundin ,&nbsp;Tyce Cave ,&nbsp;Ehraz Anis ,&nbsp;Zachary B. Madaj ,&nbsp;Christine Isaguirre ,&nbsp;Amy Johnson ,&nbsp;Ryan D. Sheldon ,&nbsp;LeAnn Smart ,&nbsp;Kipling M. Bohnert ,&nbsp;Janelle Kassien ,&nbsp;Olivia Holzgen ,&nbsp;Nagy A. Youssef ,&nbsp;Talal Khan ,&nbsp;Lena Brundin","doi":"10.1016/j.bbi.2025.106193","DOIUrl":"10.1016/j.bbi.2025.106193","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106193"},"PeriodicalIF":7.6,"publicationDate":"2025-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145630012","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":"The kynurenine pathway in pediatric “mild-to-moderate” traumatic brain injury: translational insights from a prospective human study and a large-animal model","authors":"Harm J. van der Horn ,&nbsp;Koen Visser ,&nbsp;Tracey V. Wick ,&nbsp;Samuel D. Miller ,&nbsp;Andrew P. Gigliotti ,&nbsp;Timothy B. Meier ,&nbsp;Harry van Goor ,&nbsp;T. Kent Teague ,&nbsp;Claude van der Ley ,&nbsp;Martijn van Faassen ,&nbsp;Ido P. Kema ,&nbsp;Joukje van der Naalt ,&nbsp;Andrew R. Mayer","doi":"10.1016/j.bbi.2025.106189","DOIUrl":"10.1016/j.bbi.2025.106189","url":null,"abstract":"<div><div>Elucidating the biochemical pathways affected by pediatric traumatic brain injury (TBI) is essential for identifying informative blood-based biomarkers that may support future precision medicine and clinical trials. The kynurenine pathway (KP)–the primary route for tryptophan (Trp) degradation–represents a promising candidate due to its established link to (neuro)inflammation and TBI. The current study used liquid chromatography with tandem mass spectrometry to investigate KP metabolites in serum from 54 human patients with pediatric mild TBI (pmTBI; age 8–18 years) at ∼ 7 days and ∼ 4 months post-injury and 38 age- and sex-matched healthy controls (HC). The early temporal trajectories of KP metabolites were examined in more detail in serum samples collected from 33 juvenile swine with mild-to-moderate traumatic brain injury (mmTBI) at pre-injury baseline, and at 5 min, 35 min, 2.5 h, 24 h, and 7 days post-injury. Data from 10 sham animals were collected at equivalent time points. Interleukin 1 receptor antagonist (IL-1RA), IL-1β, IL-6, IL-10 and tumor necrosis factor (TNF) α were examined as measures of inflammation. In human pmTBI, significantly lower concentrations of Trp, 3-hydroxykynurenine (3HK), 3-hydroxyanthranilic acid (3HA), xanthurenic acid (XA) and picolinic acid (PA) were observed relative to HC, with stronger effects at 4 months relative to 7 days post-injury. Lower concentrations of Trp, 3HA, and XA at 4 months were associated with persistent post-concussive symptoms (PCS). As predicted, findings for inflammatory markers were null at these time points. In the large-animal model, an increased response of the anti-inflammatory IL-1RA was found at 2.5 h post-injury in mmTBI relative to sham animals, without any group differences in KP metabolites or other inflammatory markers. Both animal groups showed prominent temporal metabolite changes, including increased Trp at 2.5 h and decreased PA up to 24 h post-injury, likely reflecting cumulative effects of isoflurane anesthesia and associated dampening of pro-inflammatory responses. Altogether, our findings indicate long-lasting effects of pmTBI on the KP in humans. Disparate profiles were observed for human and large-animal injuries, which highlights the importance of incorporating clinically relevant biomarkers in preclinical studies to improve the translation of preclinical findings into successful future clinical trials.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106189"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573108","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":"Temporally-regulated genetic access to IL-1β-expressing cellular networks in homeostasis and following peripheral or central immune stimuli","authors":"Daniel P. Nemeth ,&nbsp;Xiaoyu Liu ,&nbsp;Loretta Chen ,&nbsp;Margaret R. Hawkins ,&nbsp;Haroon S. Ali ,&nbsp;Madison G. Lapid ,&nbsp;Vesal Farsian ,&nbsp;Ashley Kim ,&nbsp;Julianna Saez ,&nbsp;Gabriella Maxey ,&nbsp;Numana Luqman ,&nbsp;Samantha McGovern ,&nbsp;Matt Schrier ,&nbsp;Chris Vargas ,&nbsp;Josh St. Juste-Ellis ,&nbsp;Jasmine Yip ,&nbsp;Joris Romain ,&nbsp;Adam D. Bachstetter ,&nbsp;Ning Quan","doi":"10.1016/j.bbi.2025.106177","DOIUrl":"10.1016/j.bbi.2025.106177","url":null,"abstract":"<div><h3>Background</h3><div>The proinflammatory cytokine Interleukin-1 beta (IL-1β) regulates nearly all aspects of immune function. In the brain, IL-1β is implicated in neural and immune functions under both basal and inflammatory conditions. Under basal conditions, IL-1β is known to alter sleep, memory, and affect. Under inflammatory conditions, IL-1β can induce sickness behaviors, HPA activation, and exacerbate neurological and psychological disorders. Sensitive detection and specific manipulation of IL-1β-expressing cells in the brain is currently not achievable; therefore, we generated the first mouse line to allow both robust visualization and genetic manipulation of the IL-1β-expressing cells.</div></div><div><h3>Methods</h3><div>The IL-1β-TRAP mouse was generated through Crispr9-mediated recombination. IRES-CreER^T2 was inserted following exon 7 after the stop codon of the <em>Il1b</em> gene which yielded an IL-1β-IRES-Cre-ER^T2 mouse (IL-1β-TRAP). To visualize IL-1β-expressing cells, IL-1β-IRES-Cre-ER^T2 line was crossed with ROSA26-lox-stop-lox-tdTomato mouse to generate the IL-1β-IRES-Cre-ER^T2:ROSA26-lox-stop-lox-tdTomato (IL-1β-TRAP-reporter). The IL-1β-TRAP-reporter mice were given intraperitoneal (i.p.) Tamoxifen before peripheral LPS or central IL-1β administration. PBS was used as control. The IL-1β-TRAP-reporter mice were also exposed to repetitive closed head injury (CHI) or i.p. kainic acid. tdTomato was allowed to express for 7d and distribution of IL-1β-expressing cells were observed via immunohistochemistry and/or lightsheet microscopy.</div></div><div><h3>Results</h3><div>Under basal conditions, IL-1β was found primarily to be expressed in MHCII⁺ and CD206⁺ meningeal and ventricular macrophages with sparse IL-1β-expressing microglia and neurons in brain parenchyma. Following i.p. LPS and i.c.v. IL-1β injections, IL-1β expression was found in meningeal macrophages and parenchymal P2YR12⁺ microglia. Following CHI, IL-1β-expressing macrophages increased in the meninges and IL-1β-expressing microglia were induced in the parenchyma at the injury site and along white matter tracts.</div></div><div><h3>Conclusions</h3><div>This is the first time active populations of cytokine-expressing cells are visualized, characterized, and genetically accessed using a mouse line with a knockin CreER. With this tool, we identified the choroid plexus as the predominant IL-1β-expressing region in homeostasis. Further, this mouse can be used to identify newly activated IL-1β-expressing cells; they can be targeted for manipulation in physiological and pathological contexts.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106177"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573052","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 microglia morphology and function across the lifespan are mediated by the early hormone environment","authors":"Lourdes K. Davis ,&nbsp;Miranda M. Anders ,&nbsp;Steven P. Guerin ,&nbsp;Sophia E. Khoury ,&nbsp;Lindsay M. Thompson ,&nbsp;Jeffrey S. Darling ,&nbsp;Andrea C. Gore ,&nbsp;Laura K. Fonken","doi":"10.1016/j.bbi.2025.106187","DOIUrl":"10.1016/j.bbi.2025.106187","url":null,"abstract":"<div><div>Microglia, the resident immune cell of the central nervous system (CNS), contribute to a range of physiological processes across the lifespan. Microglia exhibit notable sex differences in morphology, reactivity, and transcriptomic profiles. Steroid hormones in early life are believed to elicit sex differences in many cells, including microglia, in the CNS. However, few studies have examined how neonatal hormone environment impacts microglial morphology and function across the lifespan. Therefore, here we used steroid hormones to manipulate the early hormone environment to assess the appearance and persistence of sex differences in a rat model of healthy aging. Rat pups were dosed with steroid hormones on postnatal day (P)0 and 1: females received testosterone to “masculinize” them and males received flutamide, an androgen antagonist, to “feminize” them. Brain tissue was then collected at three distinct developmental timepoints: adolescence (P30), adulthood (P150), and aging (P700) for immunohistochemistry and <em>ex vivo</em> microglial stimulation. Transcriptomic changes in hippocampal tissue of aged animals were also assessed using 3’UTR biased transcriptome sequencing (Tag-seq). We report that testosterone treatment in females leads to lifelong alterations in body size and vaginal morphology and results in microglia that display a more “masculinized” phenotype compared to controls. Flutamide had more moderate effects on microglia morphology in males, contributing to a more “feminized” phenotype in the hippocampus in adult and aged males. Testosterone treatment also resulted in greater transcriptomic changes in the aged hippocampus compared to flutamide treatment, especially in genes related to mitochondrial function and inflammation. These results indicate that (1) early hormone environment is critical for the induction of sex differences in microglial morphology and (2) sex differences in microglial morphology reverse during aging, and this reversal is also recapitulated with early hormone treatment.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106187"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573046","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":"Autophagy activation by the Becn1F121A mutation reprograms neuroinflammation and promotes neurological recovery after spinal cord injury","authors":"Zhuofan Lei,&nbsp;Yun Li,&nbsp;Hui Li,&nbsp;Junfang Wu","doi":"10.1016/j.bbi.2025.106191","DOIUrl":"10.1016/j.bbi.2025.106191","url":null,"abstract":"<div><div>Autophagy is essential for maintaining cellular homeostasis, particularly under stress conditions such as neurotrauma. In experimental models of spinal cord injury (SCI), dysregulated autophagy has been closely associated with secondary injury cascades. Our previous work demonstrated that post-injury inflammation is exacerbated by genetic inhibition of autophagy and alleviated by pharmacological enhancement. Emerging evidence also indicates that SCI can induce neuropathological changes in the brain, leading to cognitive impairments; however, the underlying molecular mechanisms remain largely unclear. In this study, we utilized Becn1^F121A/F121A knock-in (BMut) mice to investigate how genetically enhanced autophagy influences transcriptomic profiles, neural cell responses, tissue pathology, and functional recovery following contusion SCI. Transcriptomic analysis of BMut mouse spinal cord (SPC) tissues at 3 days post-injury revealed enhanced autophagy flux, reduced inflammatory responses, and altered microglial function and immune activity. Ten weeks after injury, BMut mice exhibited distinct transcriptomic profiles in the SPC, somatosensory cortex, and hippocampus. Further analyses revealed that the Becn1^F121A/F121A mutation enhanced autophagy and altered inflammatory responses to SCI across all three regions. Behavioral assessments demonstrated improved functional recovery in BMut mice, accompanied by better-preserved spared white matter and reduced lesion volume. Immunofluorescence staining analysis showed that the Becn1^F121A/F121A mutation reduced microglial activation and enhanced neurogenesis in the hippocampal dentate gyrus. Our study showed that genetic enhancement of autophagy altered transcriptomic responses, particularly inflammation, after SCI, reducing neuropathology in the spinal cord and brain and improving function. This is the first evidence linking autophagy enhancement to modulation of neuroinflammation after SCI, highlighting its therapeutic potential.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"131 ","pages":"Article 106191"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145572968","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":"Searching for blood biomarkers and treatment targets in Women with fibromyalgia – Protein interaction patterns and anti-satellite glia cell IgG antibodies as promising candidates","authors":"Karolina af Ekenstam ,&nbsp;Joana Menezes ,&nbsp;Jenny E. Jakobsson ,&nbsp;Helene Silverstein ,&nbsp;Emerson Krock ,&nbsp;Jeanette Tour ,&nbsp;Katalin Sandor ,&nbsp;Alexandra Kuliszkiewicz ,&nbsp;Matthew Hunt ,&nbsp;Kim Kultima ,&nbsp;Macarena Tejos-Bravo ,&nbsp;Camilla I. Svensson ,&nbsp;Eva Kosek","doi":"10.1016/j.bbi.2025.106185","DOIUrl":"10.1016/j.bbi.2025.106185","url":null,"abstract":"<div><h3>Background</h3><div>Recent studies suggest that autoreactive immunoglobulin G (IgG) antibodies binding to satellite glia cells (anti-SGC IgG) in the dorsal root ganglia influence pain intensity in a subgroup of fibromyalgia subjects (FMS), thus indicating altered immune activation. The main aim of this study was to identify proteins distinguishing female FMS from female healthy controls (HC) and within the FM group, proteins distinguishing FMS with high vs low levels of anti-SGC IgG. The secondary aim was to assess the associations between serum proteins and anti-SGC IgG, respectively, and FM symptoms.</div></div><div><h3>Methods</h3><div>Anti-SGC IgG was quantified using an immunofluorescence assay. Proteins in serum were assessed using Olink® Explore 384 Inflammation panel, regarding differences between FMS (n = 93) and HC (n = 40) and regarding differences between FMS with high (≥50 %) and low (&lt;50 %) anti-SGC IgG, respectively. Proteins found to differ between groups (VIP ≥ 1.3) were further analyzed regarding protein-interactions using the software tool STRING (FM vs HC n = 56, high vs low anti-SGC IgG n = 55). Results from the FM group were also compared with two nociceptive pain conditions.</div></div><div><h3>Results</h3><div>In FMS, a cluster of immune system-related proteins was found among upregulated proteins, including CD40 and CD40L, with central roles in humoral immune response. CD40 levels were associated with more severe FM symptoms. In contrast, a cluster of tissue development-/regeneration-related proteins was found among downregulated proteins, this was not seen in nociceptive pain conditions. In FMS with high anti-SGC IgG, clusters dominated by immune system-related proteins were found among both upregulated and downregulated proteins. The cluster of upregulated proteins included CD79b, a protein necessary for B-cell receptor function, and CD4, a co receptor needed for T cell activation, thus with central role in activating various immune responses, including B-cell activation. Positive correlations were seen between some of these proteins and symptoms. On the contrary, several of the downregulated proteins correlated negatively to symptoms.</div></div><div><h3>Conclusion</h3><div>Our data support the involvement of the immune system in FM and indicate that further studies on autoimmune mechanisms, proteomics, and protein interaction analysis could lead to new objective diagnostic criteria identifying FMS likely to benefit from immunomodulatory treatments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"132 ","pages":"Article 106185"},"PeriodicalIF":7.6,"publicationDate":"2025-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145573069","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}