Brain, behavior, & immunity - health最新文献

{"title":"Exploring the effects of faecal microbiota transplantation on cognitive function: A review of clinical trials","authors":"Sara Alaeddin ,&nbsp;Anushka Chatterjee ,&nbsp;Tara L. Roberts ,&nbsp;Genevieve Z. Steiner-Lim ,&nbsp;Slade O. Jensen ,&nbsp;Erika Gyengesi ,&nbsp;Gerald Muench ,&nbsp;Vincent Ho","doi":"10.1016/j.bbih.2025.101049","DOIUrl":"10.1016/j.bbih.2025.101049","url":null,"abstract":"<div><div>Faecal Microbiota Transplantation (FMT) is a widely used microbiota-modulation technique to treat recurrent <em>Clostridioides difficile</em> infections (rCDI). Rodent studies and clinical trials on probiotic interventions indicate that alterations in microbiota composition may impact cognitive function. To explore whether FMT influences cognitive function in humans, we conducted a systematic search and narrative synthesis and identified 14 studies examining its effects on cognition. A variety of cohort studies, single-arm trials, case reports and randomised, placebo-controlled trials have been conducted on different neurological patient cohorts, including those with Hepatic Encephalopathy, Parkinson's Disease, dementia, and Mild Cognitive Impairment. FMT has been shown to have a significant impact on cognitive function in these populations, accompanied by alterations in microbial composition and blood markers. Interestingly, success was influenced by the route of FMT administration, indicating greater efficacy of rectal cf. oral administration on microbiome composition and cognitive improvements. However, no clinical trials have yet examined the effects of FMT on cognitively healthy individuals. FMT appears to have potential as a therapeutic strategy for cognitive impairment, though further research with larger sample sizes is needed to explore its effects in both impaired and cognitively healthy populations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101049"},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144571408","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional Mendelian randomization analysis of inflammatory factors and sleep related traits","authors":"Zaiming Liao ,&nbsp;Sheng Guo ,&nbsp;Kunying Wang ,&nbsp;Yanmin Xu ,&nbsp;Rui Zheng ,&nbsp;Binhe Yu ,&nbsp;Guoan Zhao ,&nbsp;Ruizhi Zhang ,&nbsp;Xiaohong Kang ,&nbsp;Sizhi Ai","doi":"10.1016/j.bbih.2025.101053","DOIUrl":"10.1016/j.bbih.2025.101053","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Observational research has shown significant associations between inflammatory factors and sleep. Experimental studies suggested acute increase in the levels of inflammatory markers following sleep deprivation and sleep restriction. However, the causal association between inflammatory factors and sleep remains unclear in chronic and natural settings.</div></div><div><h3>Objectives</h3><div>This study aimed to investigate the causal association of inflammatory factors with chronotype, daytime napping, daytime sleepiness, insomnia symptoms, and sleep duration.</div></div><div><h3>Methods</h3><div>Two-sample bidirectional Mendelian randomization (MR) analysis was employed to investigate the causal associations between 91 inflammatory factors and 7 sleep-related traits. Summary-level data of inflammatory factors were derived from the EBI GWAS Catalog (n = 14,824); sleep-related traits were obtained from UK Biobank. We calculated effect estimates using the inverse-variance weighted (IVW), weighted median, and MR-Egger methods. Heterogeneity and pleiotropy were detected and measured by the MR pleiotropy residual sum and outlier, Cochran's Q statistics, and MR-Egger regression.</div></div><div><h3>Results</h3><div>Significant bidirectional causal associations were observed. The most crucial findings included the causal effects of CD40 (OR = 1.02, 95 % CI: 1.01–1.03), ST1A1 (OR = 0.97, 95 % CI: 0.96–0.99), uPA (OR = 1.03, 95 % CI: 1.01–1.04) on chronotype, and FGF-21 (OR = 1.02, 95 % CI: 1.01–1.03), hGDNF (OR = 1.01, 95 % CI: 1.00–1.02), TNFB (OR = 0.99, 95 % CI: 0.98–1.00), TNFSF14 (OR = 1.01, 95 % CI: 1.00–1.02) on napping. Overall, 30 inflammatory factors were found to causally affect sleep traits, and 20 reciprocal effects were observed.</div></div><div><h3>Conclusion</h3><div>Our study suggested a bidirectional causal association between inflammatory factors and sleep-related traits, such as the roles of CD40, ST1A1, and uPA in regulating chronotype, and FGF-21, hGDNF, and TNFB in influencing daytime napping.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101053"},"PeriodicalIF":3.7,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144563252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prevalence and treatment response of neuropsychiatric disorders in mast cell activation syndrome","authors":"Leonard B. Weinstock ,&nbsp;Lawrence B. Afrin ,&nbsp;Angela M. Reiersen ,&nbsp;Jill Brook ,&nbsp;Svetlana Blitshteyn ,&nbsp;Gillian Ehrlich ,&nbsp;Jill R. Schofield ,&nbsp;Laurence Kinsella ,&nbsp;David Kaufman ,&nbsp;Tania Dempsey ,&nbsp;Gerhard J. Molderings","doi":"10.1016/j.bbih.2025.101048","DOIUrl":"10.1016/j.bbih.2025.101048","url":null,"abstract":"<div><h3>Background</h3><div>Neuropsychiatric disorders have been observed in mast cell activation syndrome (MCAS). MCAS is a common, yet rarely diagnosed, inflammatory, and immunologic disease characterized by mast cell dysregulation.</div></div><div><h3>Methods</h3><div>Questionnaires from 553 MCAS and 558 control subjects determined the prevalence and odds ratio of neurologic disorders (fatigue, cognitive dysfunction, fainting/near fainting, migraine-like headaches, muscle pain/tenderness/weakness, pain/numbness/tingling in extremities, restless legs syndrome, seizure-like activity, insomnia, sleep attacks, tinnitus, acoustic startle, Tourette's syndrome, resting tremor, and light/sun/pain/odors/scents/noise hypersensitivity) and psychiatric disorders (anxiety, agoraphobia, panic attacks, depression, bipolar depression, mania/hypomania, psychosis/schizophrenia, hallucinations, obsessive compulsive disorder, attention-deficit/hyperactivity disorder, anger management problems, post-traumatic stress disorder, suicidal thoughts, and eating disorders).</div></div><div><h3>Results</h3><div>Among 19 neurologic disorders, female MCAS patients reported higher rates in all but 1 disorder and male MCAS patients reported higher rates in all but 2 disorders. Among 14 psychiatric disorders, female MCAS patients reported higher rates in all and male MCAS patients reported higher rates in 8 disorders. Many of the disorders with increased prevalences were statistically greater compared to corresponding controls.</div><div>In self-reported ratings for effects on health status (0 = no benefit, 10 = maximum benefit), mean (SD) response was 6.3 (2.5) for antihistamines, 5.6 (3.2) for low-dose naltrexone, and 5.6 (3.1) for benzodiazepines.</div></div><div><h3>Conclusion</h3><div>MCAS subjects have significantly elevated odds ratios for many neuropsychiatric disorders and may see improvement of symptoms using MCAS-targeted therapies, suggesting that mast cell dysregulation affects the brain and peripheral nervous systems and contributes to neuropsychiatric symptoms. Certain mast cell mediators, specific genetic predisposition, and life experiences could determine which disorder is apt to develop or worsen.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101048"},"PeriodicalIF":3.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144549718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"C-reactive protein and fatigue after subarachnoid haemorrhage","authors":"Sean Daniel ,&nbsp;Ruihua Hou ,&nbsp;Ian Galea ,&nbsp;Diederik Bulters","doi":"10.1016/j.bbih.2025.101046","DOIUrl":"10.1016/j.bbih.2025.101046","url":null,"abstract":"<div><h3>Background</h3><div>Subarachnoid haemorrhage (SAH) is a severe type of intracranial bleed that causes significant morbidity. One of the most overlooked yet commonly reported symptom is persistent fatigue. Fatigue in the general population has been associated with inflammation and elevated C-reactive protein (CRP). Since inflammation and raised CRP are observed post-SAH, we hypothesized that CRP is associated with fatigue severity after SAH.</div></div><div><h3>Methods</h3><div>Data from 95 patients (26 males, 69 females; mean age 56 years) previously recruited to the SAS trial, a prospective randomised controlled trial (2016–2019) investigating the efficacy of sulforaphane after SAH, were analyzed. In this study CRP was measured on days 1, 7, and 28 post-SAH, and fatigue severity assessed using the Short-Form Health Survey (SF-36) on days 28, 90, and 180. Multivariable regression was conducted controlling for confounders, including age, gender, initial volume of blood on CT and World Federation of Neurological Surgeons (WFNS) grade.</div></div><div><h3>Results</h3><div>There was a robust association between the severity of fatigue at day 28 and CRP levels at baseline (OR = -2.67 (−1.23 to −0.18), p = 0.001) and CRP on day 28 (OR = -2.56 (−1.01 to −0.12), p = 0.013), even after controlling for confounders including blood volume and WFNS. There was no suggestion of an association between day 7 CRP and fatigue on day 28 (OR = -1.07 (−0.82 to 0.25), p = 0.287). There were no associations with any other fatigue timepoints.</div></div><div><h3>Conclusion</h3><div>CRP and fatigue in SAH patients are associated. The timings of the associations of baseline and day 28 CRP (but not day 7) with day 28 fatigue, and their independence from bleed severity suggest that fatigue is related partly to the magnitude of the initial response to the SAH and partly due to the degree of ongoing response at day 28 but not due to other events occurring in between. The lack of association of early CRP with fatigue beyond day 28 suggests that later fatigue is not driven by the initial CRP-related response to SAH. Further studies are needed to examine later CRP and the determinants of persistent fatigue.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"48 ","pages":"Article 101046"},"PeriodicalIF":3.7,"publicationDate":"2025-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144702819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proinflammatory transcriptomic and kinomic alterations in astrocytes derived from patients with familial Alzheimer's disease","authors":"Benjamin Siciliano ,&nbsp;Nicholas D. Henkel ,&nbsp;William G. Ryan V ,&nbsp;Ali Sajid Imami ,&nbsp;John M. Vergis ,&nbsp;Chongchong Xu ,&nbsp;Taylen O. Arvay ,&nbsp;Smita Sahay ,&nbsp;Priyanka Pulvender ,&nbsp;Abdul-rizaq Hamoud ,&nbsp;Chadwick Hales ,&nbsp;Robert E. McCullumsmith ,&nbsp;Zhexing Wen","doi":"10.1016/j.bbih.2025.101044","DOIUrl":"10.1016/j.bbih.2025.101044","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by profound neuronal and cognitive decline, with increasing evidence implicating astrocyte dysfunction in disease pathology. While traditional therapeutic approaches have primarily targeted neurons, the crucial role of astrocytes in metabolism, neurotransmission, amyloid-beta clearance, and neuroinflammation underscores their potential as therapeutic targets. In this study, we employed a multiomic integrative analysis combining transcriptomic and kinomic profiling of human induced pluripotent stem cell (hiPSC)-derived astrocytes from patients with familial AD (fAD) compared to healthy controls (HCs). Our transcriptomic analysis identified 1249 significantly differentially expressed genes, highlighting a pronounced upregulation of inflammatory genes (<em>SERPINA3</em>, <em>IL6R</em>, <em>IL1RAP</em>, <em>TNFRSF11A</em>) and a concomitant downregulation of genes essential for synaptic support and ion channel function (<em>STMN2</em>, <em>NMNAT2</em>, <em>SCN2A</em>, <em>GRIN1</em>). Kinomic profiling revealed dysregulated kinase activities within DYRK, GSK, and MAPK families, further implicating altered kinase signaling pathways in astrocyte dysfunction. Integration of these datasets pinpointed critical molecular hubs, notably within the PI3K signaling and inflammatory pathways, highlighting targets such as <em>JAK2</em>, <em>STAT3</em>, and <em>AKT1</em> as potential modulators of disease progression. Furthermore, leveraging the Library of Integrated Network-Based Cellular Signatures (LINCS) platform, we identified chemical perturbagens, including fluticasone propionate and Akt inhibitors, capable of reversing the transcriptomic signatures associated with fAD astrocytes. This integrative multiomic approach not only enhances our understanding of astrocyte-specific molecular mechanisms in AD but also provides novel targets for therapeutic intervention aimed at mitigating astrocyte-driven neurodegeneration.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101044"},"PeriodicalIF":3.7,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480999","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EBI2-oxysterol signalling regulates VE-cadherin expression and multiple sclerosis CD4+ T cell attachment to a human tri-cell spheroid blood-brain barrier model","authors":"Fionä Caratis ,&nbsp;Inez Mruk ,&nbsp;Klaudia Konieczna-Wolska ,&nbsp;Bartłomiej Rojek ,&nbsp;Marek Hałas ,&nbsp;Paulina Czaplewska ,&nbsp;Bartosz Karaszewski ,&nbsp;Tomomi Furihata ,&nbsp;Aleksandra Rutkowska","doi":"10.1016/j.bbih.2025.101045","DOIUrl":"10.1016/j.bbih.2025.101045","url":null,"abstract":"<div><div>Changes in the function of the blood-brain barrier (BBB) are one of the hallmarks of multiple sclerosis (MS) and are observed at very early stages of the disease. Several disease-modifying therapies for MS regulate tight junction and adherence junction proteins in the BBB thus limiting the entry of peripheral immune cells into the central nervous system (CNS). The Epstein-Barr virus-induced gene 2 (EBI2) was shown to drive immune cell migration towards high concentration of its endogenous ligand, oxysterol 7α,25OHC, which concentrations increase during inflammation in the CNS. Here, the data showed upregulated transcripts of <em>EBI2</em> and <em>CH25H</em>, the first enzyme in 7α, 25OHC synthesis pathway, in MS brain lesions. <em>In vitro</em>, cerebrospinal fluid (CSF) from patients with MS downregulated <em>HSD3B7</em>, the 7α, 25OHC degrading enzyme, and <em>VE-cadherin</em> levels in the tri-cell human BBB spheroid model. Importantly, EBI2 signalling mediated the attachment of MS patient-derived CD4⁺ T cells to the BBB spheroids. The data raises the possibility that elevated oxysterol levels in an inflamed brain might trigger a downregulation of VE-cadherin in endothelial cells, potentially easing the CNS infiltration of EBI2-expressing immune cells. This process can be modulated through the use of EBI2 ligands, suggesting a potential pathway for therapeutic intervention.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101045"},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144470972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Risk of neurodevelopmental disorders in the offspring of mothers with a history of endometriosis in Taiwanese women","authors":"Pei-Yin Yang ,&nbsp;Ching-Ming Wang ,&nbsp;Pei-Lun Liao ,&nbsp;Jing-Yang Huang ,&nbsp;Keng-Wei Liang ,&nbsp;Yu-Hsuan Lin ,&nbsp;Shun-Fa Yang ,&nbsp;Po-Hui Wang","doi":"10.1016/j.bbih.2025.101038","DOIUrl":"10.1016/j.bbih.2025.101038","url":null,"abstract":"<div><div>Several neurodevelopmental disorders have been linked to early life immune activation and inflammation, including developmental delay, cerebral palsy, intellectual disabilities, and other neurodevelopmental and psychiatric disorders. Certain inflammatory cytokines, such as interleukin-1β, interleukin-6, and tumor necrosis factor-α, secreted by endometriosis cells cause chronic pelvic inflammation and pain. The aim of this study was to evaluate whether maternal endometriosis increased the risk of neurodevelopmental disorders in offspring in <u>Taiwanese women</u>. The study included eligible mother–offspring pairs with maternal endometriosis (the case cohort) and mother–offspring pairs without maternal endometriosis (the comparison cohort) matched for maternal age at delivery, infant sex, and delivery date, both with offspring born during 2009–2016 and followed till 2019, from the Taiwan Maternal and Child Health Database. The incidence rates and crude hazard ratios (HRs) of development delay and cerebral palsy in the offspring delivered by mothers with endometriosis were higher than those in the offspring delivered by mothers without endometriosis (developmental delay: incidence 1.51 vs. 1.30 per 1000 person-months, crude HR = 1.16; cerebral palsy: incidence 0.04 vs. 0.03 per 1000 person-months, HR = 1.38). In model 1, the adjusted HRs of development delay and cerebral palsy in the offspring of mothers with endometriosis were 1.16 (95 % confidence interval [CI] = 1.11–1.22, <em>P</em> &lt; 0.0001) and 1.39 (95 % CI = 1.04–1.85, <em>P</em> = 0.0256). In model 2, these were 1.11 (95 % CI = 1.06–1.17) and 1.01 (95 % CI = 0.76–1.36), respectively. However, the HRs of intellectual disabilities and other neurodevelopmental and psychiatric disorders were not significantly different between the offspring of mothers with and without endometriosis. In conclusion, maternal endometriosis may increase the risks of cerebral palsy and specifically developmental delay in offspring.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101038"},"PeriodicalIF":3.7,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144366147","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal depressive and anxiety symptoms are associated with gut microbiota in pregnant women with overweight and obesity","authors":"Janina Hieta ,&nbsp;Chouaib Benchraka ,&nbsp;Katariina Pärnänen ,&nbsp;Noora Houttu ,&nbsp;Kati Mokkala ,&nbsp;Mrunalini Lotankar ,&nbsp;Eeva-Leena Kataja ,&nbsp;Leo Lahti ,&nbsp;Kirsi Laitinen","doi":"10.1016/j.bbih.2025.101042","DOIUrl":"10.1016/j.bbih.2025.101042","url":null,"abstract":"<div><div>The associations of gut microbiota with depressive and anxiety symptoms have been investigated mainly in non-pregnant humans, and currently there is a significant gap in research on pregnant women, especially those who are living with overweight and thus at a higher risk for experiencing perinatal mental health problems. In this study, we used shotgun metagenomic sequencing to analyze the gut microbiota of pregnant women with overweight and obesity, both in early and late pregnancy. We compared gut microbial diversity, composition, and function across groups with different trajectories of depressive (n=419) and anxiety (n=408) symptoms. Depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale (EPDS), and anxiety symptoms were evaluated with the Symptom Checklist 90 (SCL-90, anxiety subscale) at five time points spanning from early pregnancy to one year postpartum. Latent growth mixture modeling (LGMM) was used to model symptom trajectories from early pregnancy until one year postpartum and further symptom sum scores at five time points cross-sectionally. We observed differences in several bacterial species abundances between the trajectory groups and in cross-sectional analyses, including higher abundance of <em>Hungatella hathewayi</em> in the Moderate and increasing depressive symptoms group (FDR&lt;0.25), and <em>Bacteroides clarus</em> in the High and decreasing depressive symptoms group (FDR&lt;0.25) and in women experiencing clinically significant postpartum anxiety symptoms (FDR&lt;0.05). No differences were found regarding the gut microbiota diversity (α or β) or function. The results suggest that maternal gut microbiota, particularly the increased abundance of possible pro-inflammatory species, could be one of the factors affecting perinatal distress.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101042"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144480998","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dysregulated neural coding in the vagus nerve during long sepsis","authors":"Joshua J. Strohl ,&nbsp;Tomás S. Huerta ,&nbsp;Sergio Robbiati ,&nbsp;Patricio T. Huerta","doi":"10.1016/j.bbih.2025.101043","DOIUrl":"10.1016/j.bbih.2025.101043","url":null,"abstract":"<div><div>Sepsis is a life-threatening condition characterized by organ dysfunction resulting from the body's unbalanced and excessive response to an infection. ‘Long sepsis’ (LS) is an emerging concept referring to persistent sequelae experienced by long-term sepsis survivors, which include cognitive impairment, immune dysfunction, high cardiovascular risk, fatigue, and depression. Here, we investigated the role of the vagus nerve, a key component of the inflammatory reflex, in a mouse model of LS. Six weeks after cecal ligation and puncture (CLP) or sham surgery, we performed electrophysiological recordings from the cervical vagus nerve in anesthetized male mice. We found that LS mice exhibited significantly higher baseline vagal activity compared to controls, with elevated firing rates during both respiratory bursts and inter-burst intervals. Control mice showed clear increases in vagal activity following systemic administration of pro-inflammatory cytokines, tumor necrosis factor (TNF) and interleukin-1β (IL-1β), but LS mice displayed markedly dysregulated responses. LS mice showed altered firing dynamics, with many vagal units decreasing rather than increasing their activity after cytokine stimulation. Using a naïve Bayes decoder, we demonstrated that LS disrupted the neural code in the vagus nerve, significantly altering its activity pattern in response to cytokine signals. These results suggest that LS fundamentally alters vagus nerve function, with elevated baseline activity and diminished responsiveness to inflammatory signals. This neurophysiological dysregulation may contribute to the persistent multi-organ dysfunctions observed in long sepsis survivors, suggesting a potential role for vagal signaling in sepsis outcomes.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101043"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144335643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Parasympathetic nervous activity and CTRA gene expression among healthy young adults in Japan","authors":"Yoshino Murakami ,&nbsp;Takeshi Hashimoto ,&nbsp;Steve Cole","doi":"10.1016/j.bbih.2025.101040","DOIUrl":"10.1016/j.bbih.2025.101040","url":null,"abstract":"<div><div>Previous research suggests that parasympathetic nervous system (PNS) activity may inhibit the leukocyte Conserved Transcriptional Response to Adversity (CTRA) which has been observed in individuals exposed to prolonged stressors like loneliness, social isolation, and bereavement. Previous PNS-CTRA studies have focused on Western populations, raising questions about the generalizability of these findings across different cultural and ethnic backgrounds. This study examined the relationship between PNS activity (as indexed by heart rate variability; HRV) and CTRA gene expression in young, healthy adults in Japan (n = 26; Mean age = 26; 34.6 % female). In analyses that controlled for demographic and behavioral covariates (including age, sex, ethnicity, smoking, alcohol, and BMI), results showed a significant inverse relationship between HRV and CTRA gene expression (i.e., lower expression of pro-inflammatory genes and elevated expression of Type I interferon response genes). Convergent validation analyses of genome-wide transcription factor activity linked HRV to up-regulation of Interferon Response Factors and down-regulation of NF-κB. These results parallel previous findings from Western samples, confirming that PNS neuro-immune regulation generalizes to an population based in Japan, as part of broader East Asian region and identifying HRV as a useful index for optimizing immune health in diverse populations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"47 ","pages":"Article 101040"},"PeriodicalIF":3.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144489689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}