Brain, Behavior, and Immunity最新文献

{"title":"Gut microbiota links vitamin C supplementation to enhanced mental vitality in healthy young adults with suboptimal vitamin C status: A randomized, double-blind, placebo-controlled trial","authors":"Minju Sim ,&nbsp;Sehwa Hong ,&nbsp;Min Ho Jung ,&nbsp;Eun Young Choi ,&nbsp;Geum-Sook Hwang ,&nbsp;Dong-Mi Shin ,&nbsp;Chong-Su Kim","doi":"10.1016/j.bbi.2025.03.032","DOIUrl":"10.1016/j.bbi.2025.03.032","url":null,"abstract":"<div><div>The intricate relationship between nutrition, gut microbiome, and mental health has gained increasing attention. We aimed to determine how vitamin C supplementation improves mental vitality through the gut microbiome and associated neurological and immunological changes. We used 16S rRNA sequencing to analyze gut microbiota profiles of participants from our previous trial, in which healthy young adults (20–39 years) with inadequate serum vitamin C levels (&lt; 50 μM) received 500 mg vitamin C or a placebo twice daily for 4 weeks (vitamin C, <em>n</em> = 21; placebo, <em>n</em> = 19). We examined whether changes in gut microbiota correlated with previously determined mental vitality indices, including Stroop test performance, work engagement, and serum brain-derived neurotrophic factor (BDNF) levels. Serum concentrations of microbial-derived molecules, cytokines, and neurotransmitters were analyzed using enzyme-linked immunosorbent assay, electrochemiluminescence-based immunoassay, or ultra-high-performance liquid chromatography–mass spectrometry. Monocyte subpopulations in peripheral blood were quantified using fluorescence-activated cell sorting analysis. Vitamin C supplementation increased the relative abundance of Bacillaceae and <em>Anaerotruncus</em>, while decreasing <em>Desulfovibrio</em>, with the <em>Desulfovibrio</em> reduction correlating with Stroop test performance. Moreover, participants showing a substantial <em>Desulfovibrio</em> reduction (“responders”) demonstrated greater BDNF increases and stronger correlations between serum L-DOPA levels and work engagement scores than did non-responders. In addition, vitamin C supplementation suppressed inflammatory responses with concurrent reduction in serum lipopolysaccharide levels, and responders showed greater decreases in IL-10 levels and classical monocyte frequencies than non-responders. In conclusion, vitamin C supplementation modulates gut microbiota composition, particularly by reducing <em>Desulfovibrio</em> abundance, with the extent of reduction correlating with mental vitality improvements and decreased inflammation. This study provides insights into vitamin C supplementation as a critical dietary intervention, as it may modulate mental health through its influence on the gut-brain-immune axis.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 179-191"},"PeriodicalIF":8.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787951","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":"Perinatal exposure to polystyrene nanoplastics alters socioemotional behaviors via the microbiota–gut–brain axis in adult offspring mice","authors":"Yi Guo ,&nbsp;Mei Li ,&nbsp;Xiaoyu Liu ,&nbsp;Huiling Duo ,&nbsp;Boya Huang ,&nbsp;Hengtai Lu ,&nbsp;Xiangyu Zhang ,&nbsp;Xuzhe Li ,&nbsp;Ye Zhao ,&nbsp;Kaoqi Lian ,&nbsp;Tengfei Liu ,&nbsp;Yun Shi ,&nbsp;Yuan Gao ,&nbsp;Li Meng ,&nbsp;Di Zhao ,&nbsp;Li Song ,&nbsp;Rui Jiang ,&nbsp;Haishui Shi","doi":"10.1016/j.bbi.2025.04.002","DOIUrl":"10.1016/j.bbi.2025.04.002","url":null,"abstract":"<div><div>Polystyrene nanoplastics (PS-NPs), ubiquitous environmental contaminants, have been detected in various tissues of humans and animals, raising significant concerns regarding their potential health hazards. The long-term consequences of PS-NPs exposure during early developmental stages remain inadequately characterized. In this study, we established a murine model to investigate the chronic oral administration of PS-NPs via drinking water during the perinatal period, with a focus on elucidating the impact of PS-NPs ingestion on the social behaviors of adult offspring and the underlying mechanisms, particularly those involving the gut–brain axis. Our findings revealed that perinatal PS-NPs exposure elicited depression-like behaviors, diminished social dominance, and reduced social interactions in adult offspring. Additionally, we observed a decrease in dendritic spine density within hippocampal neurons, along with ultrastructural damage to hippocampal neurons and synapses in the adult offspring. PS-NPs exposure also led to a reduction in the richness and evenness of gut microbiota species composition in both male and female mice, with gut dysbiosis being particularly pronounced in adult males. Furthermore, alterations in metabolite abundance and metabolic pathways were detected in the hippocampus of both male and female adult offspring. Notably, a significant correlation was identified between the relative abundance of intestinal microorganisms and hippocampal metabolites. These results offer new insights into the association between early-life PS-NPs exposure and adult social behaviors, mediated through the microbiota–gut–brain axis.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 121-133"},"PeriodicalIF":8.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787956","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-specific effects of chronic alcohol consumption across the lifespan in the transgenic Alzheimer’s Disease (TgF344-AD) rat model","authors":"Paige Marsland,&nbsp;Andrew S. Vore,&nbsp;Ashley Lutzke,&nbsp;Anny Gano,&nbsp;Abigail Fischer,&nbsp;Sarah Trapp,&nbsp;Lisa M. Savage,&nbsp;Terrence Deak","doi":"10.1016/j.bbi.2025.03.034","DOIUrl":"10.1016/j.bbi.2025.03.034","url":null,"abstract":"<div><div>Alcohol consumption across the lifespan contributes to mood fluctuations and cognitive dysfunction, two neurobehavioral features also associated with Alzheimer’s Disease and Related Dementias (ADRD). Yet, few studies have used rodent models to determine how a history of ethanol consumption across the lifespan might contribute to neurobehavioral and neuropathological features of ADRD. We exposed Wild Type (WT) and transgenic Fischer 344 CE rats (TgF344-AD) that have been genetically modified to express the human Amyloid Precursor Protein (APP) and presenilin-1 genes with mutations, to ethanol using a chronic, intermittent ethanol consumption model. Beginning at P28, rats were given a single bottle 10 % ethanol solution for 2 consecutive days, followed by 2 days of tap water. This pattern (2 days on, days off) was repeated for a total of 12 cycles until rats reached the age of ∼ 3 months, and repeated at 6 (Exp 1 and Exp 2) and 9 months of age (Exp 2). In experiment 1, ethanol consumption decreased alternations in a spontaneous alternation task in females, only at the 3-month time point, whereas TgF344-AD females showed increased contextual fear conditioning in the test of retention and reinstatement tests at 6 months of age. In experiment 2, a battery of anxiety-like behaviors (Elevated Plus Maze, Marble Burying, and Novelty Induced Hypophagia) were assessed following a 2-week abstinence period at 3, 6, and 9 months of age in ethanol-consuming rats. Data from the EPM and marble burying tasks revealed evidence of heightened anxiety-like behavior in Tg-F344-AD rats that varied by sex and age, with no significant effects of ethanol. In the novelty-induced hypophagia task, males with a history of ethanol consumption had a lower latency to approach a familiar, salient reward at 3 months old, but effects of ethanol were overall minimal. Examination of dorsal hippocampal gene expression at 6 months of age under basal conditions also revealed predominantly genotype and sex-specific effects on inflammation- and AD-related genes (<em>App, Il-6, Bace1, Rage, Lrp-1</em>). When examined at 9 months old following LPS challenge, ethanol increased inflammatory genes in males (<em>Il-1β, Il-6</em>) in the hippocampus, whereas ethanol decreased several inflammatory and AD-related genes (<em>Hmgb1, Rage, Bace1, Lrp-1</em>) in TgF344-AD females. Overall, these data provide further evidence that females are especially vulnerable to AD, and that a history of ethanol consumption had selective, rather than global, effects on AD- and inflammation-related genes following an inflammatory stimulus.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 192-207"},"PeriodicalIF":8.8,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787570","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":"Minocycline treatment attenuates neurobehavioural abnormalities and neurostructural aberrations in the medial prefrontal cortex in mice fed a high-fat diet during adolescence","authors":"Yuxi Chen ,&nbsp;Xiuting Yao ,&nbsp;Conghui Wang ,&nbsp;Hong Zhuang ,&nbsp;Bingjie Xie ,&nbsp;Congli Sun ,&nbsp;Zixuan Wang ,&nbsp;Xinguo Zhou ,&nbsp;Yu Luo ,&nbsp;Yilin Zhang ,&nbsp;Shihui Zhou ,&nbsp;Lijie Liu","doi":"10.1016/j.bbi.2025.03.035","DOIUrl":"10.1016/j.bbi.2025.03.035","url":null,"abstract":"<div><div>A preference for and overconsumption of a high-fat diet (HFD) are common among adolescents and are recognized as risk factors for multiple mental disorders. The protracted maturation of the medial prefrontal cortex (mPFC), a key brain structure that plays a critical role in mental functions that are essential for both developing and mature individuals (including emotional processing, decision making, risk assessment, and creative thinking), during adolescence renders it more vulnerable to the environmental insults experienced during this critical developmental window. However, the effects of HFD consumption during adolescence on mPFC-related behaviours and the underlying mechanisms need to be further investigated. In this study, we observed that mice fed a HFD throughout adolescence developed depressive- and anxiety-like behaviours and distinctively increased risk-avoidance behaviour, accompanied by morphological aberrations of both pyramidal neuron and microglia in the mPFC. The systemic administration of minocycline, a well-known broad-spectrum antibiotic, effectively attenuated the adverse effects of HFD consumption during adolescence on neurobehaviours and the morphology of pyramidal neurons in the mPFC. This study provides new insights into the psychological effects of long-term HFD consumption during adolescence and indicates the existence of a window during which microglial stabilization may be a promising strategy to protect against the HFD consumption-induced increase in the risk of psychiatric disorders.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 83-98"},"PeriodicalIF":8.8,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769047","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":"TLR9 in satellite glial cells promotes paclitaxel-induced neuropathic pain by reducing Kir4.1 transcription through histone methylation activation","authors":"Qingtian Luo ,&nbsp;Jian Jiang ,&nbsp;Qing Zhu ,&nbsp;Sashuang Wang ,&nbsp;Yifei Wu ,&nbsp;Nan Li ,&nbsp;Xiyuan Ba ,&nbsp;Fengling Wu ,&nbsp;Xu Liu ,&nbsp;Yuhui Luo ,&nbsp;Donglin Xiong ,&nbsp;Lizu Xiao ,&nbsp;Xiang Liao ,&nbsp;Zhenhe Huang ,&nbsp;Zixian Chen ,&nbsp;Changyu Jiang","doi":"10.1016/j.bbi.2025.03.037","DOIUrl":"10.1016/j.bbi.2025.03.037","url":null,"abstract":"<div><div>Chemotherapy-induced neuropathic pain (CINP), commonly induced by paclitaxel (PTX), is a debilitating side effect that often leads to the discontinuation of cancer treatment. Despite its significant impact on patients’ quality of life, the mechanisms underlying CINP remain poorly understood. Recent studies have suggested that immune system activation, particularly through Toll-like receptor 9 (TLR9), plays a crucial role in the development of neuropathic pain. In this study, we investigated the involvement of TLR9 in PTX-induced CINP, with a focus on satellite glial cells (SGCs) in the dorsal root ganglion (DRG). We found that TLR9 expression was significantly upregulated in SGCs following PTX treatment, and its activation contributed to the downregulation of Kir4.1 (potassium inwardly rectifying channel, subfamily J, member 10), a key potassium channel that regulates neuronal excitability. This process was mediated through histone methylation, involving the methyltransferase G9a and the NF-κB signaling pathway. Inhibition of TLR9 or knockdown of its expression alleviated PTX-induced pain behaviors while inhibiting G9a restored Kir4.1 function and reduced pain. These findings suggest that TLR9 and its downstream signaling pathways, including G9a-mediated histone modification, play a critical role in the development of CINP. Targeting TLR9 and histone methylation may provide novel therapeutic strategies for managing CINP and improving cancer treatment outcomes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 65-82"},"PeriodicalIF":8.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143769046","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 effects of P2Y12 loss on microglial gene expression, dynamics, and injury response in the cerebellum and cerebral cortex","authors":"Mark B. Stoessel ,&nbsp;Rianne D. Stowell ,&nbsp;Rebecca L. Lowery ,&nbsp;Linh H.D. Le ,&nbsp;Andy N. Vu ,&nbsp;Brendan S. Whitelaw ,&nbsp;Ania K. Majewska","doi":"10.1016/j.bbi.2025.03.036","DOIUrl":"10.1016/j.bbi.2025.03.036","url":null,"abstract":"<div><div><ul><li><span></span><span><div>Despite the emerging consensus that microglia are critical to physiological and pathological brain function, it is unclear how microglial roles, and their underlying mechanisms differ between brain regions. Microglia throughout the brain express common markers, such as the purinergic receptor P2Y12, that delineate them from monocytes and brain macrophages. P2Y12 is a critical sensor of injury but also contributes to the sensing of neuronal activity and remodeling of synapses, with microglial loss of P2Y12 resulting in behavioral deficits. P2Y12 has largely been studied in cortical microglia, despite the fact that a growing body of evidence suggests that microglia exhibit a high degree of regional specialization. Cerebellar microglia, in particular, exhibit transcriptional, epigenetic, and functional profiles that set them apart from their better studied cortical and hippocampal counterparts. Here, we demonstrate that P2Y12 is required for a full microglial response to focal injury in the cortex but not in the cerebellum, suggesting that cerebellar and cortical microglia utilize P2Y12 signaling differently. We therefore investigated the effects of P2Y12 deficiency on cerebellar microglial physiology and function, and overall contributions to synaptic plasticity. We found that P2Y12 deficiency does little to disturb the distinct transcriptomic profiles of cortical and cerebellar microglia and does not alter the morphology, distribution, or homeostatic dynamics of microglia in the cerebellum. However, we show that P2Y12 deficiency impairs cerebellar learning in a delay eyeblink conditioning task, a common test of cerebellar plasticity and circuit function. Overall, our findings suggest not only region-specific roles of microglial P2Y12 signaling in the focal injury response, but also indicate a conserved role for P2Y12 in microglial modulation of plasticity across regions.</div></span></li></ul></div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 99-120"},"PeriodicalIF":8.8,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143768981","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":"CCL25 in the cerebrospinal fluid is negatively correlated with fatigue in chronic pain patients","authors":"Alexander H.C. Rosenström ,&nbsp;Aisha Siddiqah Ahmed ,&nbsp;Alex Bersellini Farinotti ,&nbsp;Kim Kultima ,&nbsp;Svante Berg ,&nbsp;Martin F. Bjurström ,&nbsp;Camilla I. Svensson ,&nbsp;Eva Kosek","doi":"10.1016/j.bbi.2025.03.030","DOIUrl":"10.1016/j.bbi.2025.03.030","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background and aim&lt;/h3&gt;&lt;div&gt;Chronic pain is often accompanied by other symptoms such as fatigue and sleep disturbance, and these symptoms all correlate with neuroimmune activation. However, their relation to one another on a neuroimmune axis remains elusive. Based on a recent review, cytokines in the cerebrospinal fluid (CSF) seem to be generally upregulated in patients with chronic pain compared to controls, disregarding pain type. Some of these have the possilibity of altering blood–brain barrier (BBB) permeability. Therefore, cytokine levels in serum and CSF, as well as BBB permeability, were measured in a cohort of patients suffering from either degenerative disc disease (DDD), lumbar disc herniation (LDH) or osteoarthritis (OA). In this exploratory study, we were interested in whether cytokines in the serum or CSF are associated with sleep disturbance or fatigue, with special consideration of the effect of BBB permeability, and whether functional clusters can be found among these cytokines.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;One-hundred-twenty patients with DDD/LDH/OA, all awaiting surgery, were included. Blood and CSF were collected on the day of surgery. Pain was measured with a visual analog scale 0–100 mm, sleep disturbance was assessed using Pittsburgh Sleep Quality Index (PSQI), and fatigue was measured using the Multidimensional Fatigue Inventory (MFI). A 92-protein multiplex panel (OLINK, Sweden) was used to analyze cytokine expression in serum and CSF, respectively. CSF-serum albumin quotient was measured using ELISA. Non-parametric statistics were used for univariate analyses, and a false discovery rate (FDR) &lt; 0.10 was considered statistically significant. Bonferroni correction was applied to all multivariable protein analyses to obtain conservative effect estimates.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Main results&lt;/h3&gt;&lt;div&gt;There was an association between BBB permeability and serum-CSF dynamics: thirty-one cytokines showed significant CSF-serum correlation, and BBB permeability was significantly correlated to the quotients of 35 cytokines and to the CSF levels of 11 cytokines. Several cytokines were negatively correlated to both pain at rest and general fatigue. No correlations were found between sleep disturbance and cytokines. Network analyses of serum and CSF cytokines that were correlated with fatigue revealed functional clusters in both compartments. Anxiety, depression, and pain during rest were important regressors for sleep disturbance with an R&lt;sup&gt;2&lt;/sup&gt; = 0.41. In addition to depression and pain during rest, CSF levels of CCL25 was a significant regressor regarding general fatigue, with an R&lt;sup&gt;2&lt;/sup&gt; = 0.47.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Discussion and conclusion&lt;/h3&gt;&lt;div&gt;In this exploratory study of immune profiles in chronic pain cohorts awaiting surgery, the importance of BBB dynamics on serum-CSF cytokine dynamics, and to a lesser extent on central levels of cytokines, is highlighted. Surprisingly, there were no association","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 54-64"},"PeriodicalIF":8.8,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143751218","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":"Elevated neuroinflammation, autoimmunity, and altered IgG glycosylation profile in the cerebral spinal fluid of severe COVID-19 patients","authors":"Tanner Shull ,&nbsp;Pavan Bhimalli ,&nbsp;Samantha Welninski ,&nbsp;Byoung-Kyu Cho ,&nbsp;Basil Mattamana ,&nbsp;Jaison Arivalagan ,&nbsp;Imad Tarhoni ,&nbsp;Young Ah Goo ,&nbsp;Julie A. Schneider ,&nbsp;Sonal Agrawal ,&nbsp;David A Bennett ,&nbsp;Sue Leurgans ,&nbsp;Mayur B. Patel ,&nbsp;E.Wesley Ely ,&nbsp;Neil L. Kelleher ,&nbsp;Jeffrey A. Borgia ,&nbsp;Jeffrey R. Schneider ,&nbsp;Lena Al-Harthi","doi":"10.1016/j.bbi.2025.03.031","DOIUrl":"10.1016/j.bbi.2025.03.031","url":null,"abstract":"<div><h3>Background and Objectives</h3><div>A spectrum of neurologic complications associated with COVID-19 are well documented. While neuroinflammation in the brain of COVID-19 patients likely contributes to these complications, the mechanisms of neuroinflammation and correlates of neurologic complications remain elusive, especially since the etiologic pathogen of COVID-19, SARS-CoV-2, minimally invades the CNS. This study aimed to evaluate markers of neuroinflammation, IgG glycosylation patterns indicative of pro- or anti-inflammatory state, and prevalence of brain auto-reactive antibodies in the CSF of COVID-19 patients and their relationship to brain neuropathology.</div></div><div><h3>Methods</h3><div>We evaluated the CSF of 11 deceased unvaccinated COVID-19 donors and 13 matched non-COVID-19 controls. Markers of neuroinflammation, IgG glycosylation patterns, and brain auto-reactive antibodies were assessed, along with their correlation to brain neuropathology. Statistical analyses were performed to compare groups and assess relationships between variables, using non-parametric tests and bootstrap analysis.</div></div><div><h3>Results</h3><div>COVID-19 CSF showed higher levels of neopterin and ANNA-1, markers of neuroinflammation and autoimmunity, respectively, and lower IFN response compared to non-COVID-19 donors. In brain regions of high microglial activation, IL4 and RANTES were significantly increased. SARS-CoV-2 was undetectable in the CSF and brain of COVID-19 donors, yet anti-SARS-CoV-2 CSF antibodies were detected. Fucosylated IgG were associated with Spike IgG, CSF protein, and soluble CD14, whereas afucosylated bisecting IgG were inversely correlated with Spike IgG. Sialic acid containing IgG were positively correlated with IL1β and TNFα. These associations were not found in non-COVID-19 donors. Inflammatory agalactosylated fucosylated IgG (G0F) were associated with infiltrating CD4 + T cells in the brains of COVID-19 donors. COVID-19 donor CSF displayed higher levels of auto-reactive antibodies to human brain antigens compared to non-COVID-19 donors and donors with positive autoantibodies showed higher levels of neopterin.</div></div><div><h3>Discussion</h3><div>These data describe increased neuroinflammation and autoreactive antibody markers in the CSF of COVID-19 donors and suggest that IgG glycosylation and autoimmunity may contribute to COVID-19 pathology, highlighting potential mechanisms underlying the neurologic complications associated with COVID-19.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 289-302"},"PeriodicalIF":8.8,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143742353","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":"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}