Brain, behavior, & immunity - health最新文献

{"title":"Functional olfactory impairment and fatigue in post-COVID-19 syndrome including ME/CFS – a longitudinal prospective observational study","authors":"Lil Meyer-Arndt ,&nbsp;Greta Pierchalla ,&nbsp;Lukas Mödl ,&nbsp;Felix Wohlrab ,&nbsp;Franziska Legler ,&nbsp;Uta Hoppmann ,&nbsp;Claudia Kedor ,&nbsp;Kirsten Wittke ,&nbsp;Helma Freitag ,&nbsp;Frank Konietschke ,&nbsp;Heidi Olze ,&nbsp;Friedemann Paul ,&nbsp;Carmen Scheibenbogen ,&nbsp;Judith Bellmann-Strobl ,&nbsp;Ulrike Förster-Ruhrmann","doi":"10.1016/j.bbih.2025.101124","DOIUrl":"10.1016/j.bbih.2025.101124","url":null,"abstract":"<div><div>Post-COVID-19 syndrome (PCS) affects a significant proportion of individuals, with olfactory impairment and fatigue as prominent long-term symptoms. A subset of PCS patients with pronounced fatigue meets the diagnostic criteria for myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), here referred to as PCS-ME/CFS. This study explores the relationship between PCS, fatigue, and olfactory function, and investigates the potential of olfactory impairment as a diagnostic and prognostic marker.</div><div>We assessed olfactory function up to 28 months post-COVID-19 in 45 PCS patients (22 PCS, 23 PCS-ME/CFS) using the extended Sniffin’ Sticks test, which evaluates odor threshold, discrimination, and identification, providing a composite score. Fatigue severity and health-related quality of life were assessed using validated questionnaires, a standardized test measured cognitive function, and handgrip strength indicated physical fatiguability.</div><div>Both PCS and PCS-ME/CFS patients showed significant improvement in olfactory function, with all patients returning to normosmia after 20 months, regardless of diagnosis. While odor threshold was the most affected olfactory measure in Sniffin’ Sticks testing, odor identification was the only measure that remained impaired over time. Olfactory impairment correlated with cognitive, physical, and mental performance, with stronger correlations in the PCS group, particularly linking better odor discrimination at baseline to improved daily functioning and health-related quality of life after 20 months.</div><div>Our findings suggest that odor identification assessed in standardized testing may remain impaired the longest in patients with persisting symptoms after COVID-19, reflecting persisting central processing difficulties. Correlations between olfactory performance, cognitive function, and physical ability point to shared underlying mechanisms. Early olfactory improvements may be linked to better long-term cognitive outcomes, highlighting a possible prognostic role of olfactory function in these patients.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"50 ","pages":"Article 101124"},"PeriodicalIF":3.5,"publicationDate":"2025-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145428836","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":"Combined effects of calorie restriction and chronic stress on systemic inflammation and gut microbiota in rats exposed to Leptospira interrogans lipopolysaccharide","authors":"Pavlo Petakh ,&nbsp;Yaroslav Stravskyy ,&nbsp;Iryna Halabitska ,&nbsp;Alina Pavliuk ,&nbsp;Oleksandr Kamyshnyi","doi":"10.1016/j.bbih.2025.101121","DOIUrl":"10.1016/j.bbih.2025.101121","url":null,"abstract":"<div><h3>Background</h3><div>Calorie restriction (CR) is widely studied for its anti-inflammatory and immunomodulatory effects. However, under conditions of chronic stress—such as those experienced during war, displacement, or famine—its impact on immune function remains poorly understood. In such contexts, combined nutritional and psychosocial stress may exacerbate inflammation and compromise host defences against pathogens.</div></div><div><h3>Objective</h3><div>To investigate how the combination of moderate calorie restriction and chronic social stress affects systemic immune responses and gut microbiota composition following exposure to <em>Leptospira interrogans</em> lipopolysaccharide (LPS) in rats.</div></div><div><h3>Methods</h3><div>Male Wistar rats were assigned to either <em>ad libitum</em> feeding (control) (n = 6), calorie restriction (CR, 30 % reduction) (n = 12), or CR combined with chronic overcrowding stress for 14 days (n = 12). All animals were subsequently challenged with <em>Leptospira</em> LPS. Immune gene expression was analyzed in peripheral blood using RT-qPCR arrays. Culture-based quantification of fecal microbiota was performed to assess compositional changes. Correlations between microbiota and cytokine gene expression were evaluated.</div></div><div><h3>Results</h3><div>Compared with the control group, CR increased <em>Il10</em> expression and increased the abundance of beneficial bacteria such as <em>Lactobacillus</em> and <em>Bifidobacterium</em>, suggesting an anti-inflammatory and microbiota-supportive effect. In contrast, relative to the CR-only group, rats exposed to CR combined with chronic social stress showed marked upregulation of pro-inflammatory cytokine genes (<em>Il1b</em>, <em>Il6</em>, <em>Tnf</em>) and a shift toward gut dysbiosis, characterized by increased abundance of <em>Klebsiella</em> spp., <em>Escherichia coli</em>, and <em>Enterococcus</em> species.</div></div><div><h3>Conclusion</h3><div>A combination of chronic stress and calorie restriction can promote inflammation and cause gut dysbiosis, which may lead to a more severe form of leptospirosis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101121"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325426","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":"Integrative evidence for causal links between gut microbiota and Schizophrenia: A Mendelian randomization and 16S rRNA study","authors":"Jianye Zeng ,&nbsp;Xiumei Zhu ,&nbsp;Huajie Ba ,&nbsp;Shilin Li ,&nbsp;Chun Yang ,&nbsp;Ping Huang ,&nbsp;Anqi Chen ,&nbsp;Yingnan Bian ,&nbsp;Chengtao Li ,&nbsp;Suhua Zhang","doi":"10.1016/j.bbih.2025.101123","DOIUrl":"10.1016/j.bbih.2025.101123","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia is a severe psychiatric disorder with a complex etiology. Emerging evidence implicates the gut microbiota in its pathogenesis via the microbiota-gut-brain axis, although causal relationships remain unclear.</div></div><div><h3>Methods</h3><div>We used a two-sample Mendelian randomization (MR) approach to investigate potential causal links between gut microbial taxa and schizophrenia. To provide a biological context for these findings, we performed 16S rRNA V3-V4 sequencing of fecal samples from an independent cohort of individuals with schizophrenia (SCZ, n = 21) and matched healthy controls (HC, n = 21).</div></div><div><h3>Results</h3><div>Forward MR analysis revealed a significant causal association between seven microbial taxa and schizophrenia risk. Notably, a higher genetically predicted abundance of <em>Bifidobacterium</em> was associated with increased schizophrenia risk (OR = 1.47, 95 %CI: 1.05–2.05), with results robust to multivariable adjustment. Reverse MR found no evidence of reverse causation. In the independent cohort, exploratory 16S rRNA analysis of the top 15 most abundant genera revealed nominal differences, including <em>Bifidobacterium</em>, <em>Megamonas</em>, <em>Streptococcus</em>, and <em>Fusicatenibacter</em>, but none remained significant after FDR correction (all <em>Q</em> &gt; 0.05). However, a targeted confirmatory analysis of four MR-identified taxa revealed significant group differences for three taxa (all <em>Q</em> = 0.010), whereas <em>Lachnospiraceae</em> did not.</div></div><div><h3>Conclusions</h3><div>By integrating MR with 16S rRNA V3-V4 sequencing, this study provides convergent evidence for a potential causal role of specific gut microbial taxa, particularly <em>Bifidobacterium</em>, in contributing to schizophrenia risk. Our findings underscore the context-dependent nature of host-microbiota interactions and support the need for strain-level and functional studies to further elucidate schizophrenia pathogenesis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101123"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363582","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":"Interleukin-6 moderates the relationship between social support, strain, and future depressive symptoms","authors":"Timothy Bang Hao Aw,&nbsp;Nur Hani Zainal","doi":"10.1016/j.bbih.2025.101122","DOIUrl":"10.1016/j.bbih.2025.101122","url":null,"abstract":"<div><h3>Background</h3><div>Inflammation has been increasingly implicated in major depressive disorder (MDD), with interleukin-6 (IL-6) emerging as a key biomarker. How this relates to psychosocial risk factors, such as social support and strain, remains underexplored. IL-6 levels, social support, and strain may interact through shared underlying mechanisms in conferring depression risk. The study examined whether IL-6 levels moderate the associations between social support and strain with future MDD symptoms.</div></div><div><h3>Methods</h3><div>Longitudinal data from 1,054 community adults in the Midlife Development in the United States (MIDUS) study were analyzed. Multiple linear regression models examined the main and interactive effects of social support, social strain, and IL-6 on future MDD symptoms. Serum IL-6 levels were measured using both enzyme-linked immunosorbent assay (ELISA) and Meso Scale Discovery (MSD) immunoassays, with results cross-examined. Sensitivity analyses, including generalized additive models (GAM) and covariate-adjusted models, were conducted to account for potential nonlinearities and confounders.</div></div><div><h3>Results</h3><div>Lower social support and greater social strain predicted higher future MDD symptoms, particularly among individuals with elevated IL-6 levels. The interaction between social strain and IL-6 levels was robust across both ELISA (<em>d</em> = 0.18, <em>p</em> = .003) and MSD-derived (<em>d</em> = 0.12, <em>p</em> = .048) assay methods. In contrast, the interaction between social support and IL-6 was observed only in ELISA-based measurements (<em>d</em> = −0.13, <em>p</em> = .033).</div></div><div><h3>Conclusion</h3><div>IL-6 levels may moderate the relationship between social support, strain, and future MDD symptoms. Interpersonally-focused interventions enhancing social support or mitigating strain may consider the potential interacting role of inflammation in alleviating the psychosocial risk of depression.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101122"},"PeriodicalIF":3.5,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145363581","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":"Acute and chronic nasal inflammation induces lymphangiogenesis in the olfactory mucosa in mice","authors":"Suzuho Komaki ,&nbsp;Ryuichi Imai ,&nbsp;Yuzuki Sugimoto ,&nbsp;Rei Settsu ,&nbsp;Aki Obara ,&nbsp;Atsuyoshi Shimada ,&nbsp;Robert Dantzer ,&nbsp;Geoffroy Laumet ,&nbsp;Fumiaki Imamura ,&nbsp;Sanae Hasegawa-Ishii","doi":"10.1016/j.bbih.2025.101119","DOIUrl":"10.1016/j.bbih.2025.101119","url":null,"abstract":"<div><h3>Background</h3><div>Lymphangiogenesis, the formation of new lymphatic vessels, is primarily driven by VEGF-C-mediated activation of VEGFR-3 and plays a critical role in immune regulation and tissue repair. Although lymphangiogenesis has been well documented in various inflamed tissues, its occurrence and spatiotemporal characteristics in the olfactory mucosa during nasal inflammation remain poorly understood. To address this, we investigated the localization and development of lymphatic vessels in a mouse model of both acute and chronic nasal inflammation.</div></div><div><h3>Methods</h3><div>Acute inflammation was induced by intranasal administration of lipopolysaccharide (LPS; 10 μg per nostril) in 8-week-old male mice, with saline-treated mice as controls. Behavioral tests were conducted at 24 and 48 h post-administration. Nasal tissues were collected at multiple time points up to four weeks. Cytokine expression was analyzed by quantitative RT-PCR, and VEGF levels were quantified using ELISA. Immune cell infiltration and lymphatic vessel localization were assessed histologically using markers such as Lyve-1, VEGFR-3, and Prox-1. For the chronic inflammation model, mice received unilateral intranasal LPS or saline administration three times per week for 10 weeks, followed by histological analysis of lymphatic remodeling.</div></div><div><h3>Results</h3><div>Mice showed transient reduction in food and water intake and body weight, some aspects of sickness behavior within 24 h, but did not display depression-like phenotypes at 24 and 48 h post-LPS, as measured by duration of immobility in the tail suspension test and forced swim test, and percent sucrose volume consumed in the sucrose preference test. LPS treatment induced a sustained inflammatory response, with elevated pro- and anti-inflammatory cytokine expression persisting for up to two weeks. Immune cell infiltration and lymphangiogenesis were localized to specific areas of the olfactory mucosa, particularly the inner regions of the first and second turbinates. These inflammatory hotspots exhibited increased expression of lymphatic markers, primarily due to proliferation of lymphatic endothelial cells. VEGF-C and VEGF-A levels were significantly upregulated following LPS treatment. In the chronic model, lymphangiogenesis became more widespread throughout the olfactory mucosa, and was accompanied by dense infiltration of CD11b + immune cells.</div></div><div><h3>Conclusions</h3><div>Nasal inflammation induces region-specific lymphangiogenesis during the acute phase, likely driven by local proliferation of lymphatic endothelial cells. Under chronic inflammatory conditions, both inflammation and lymphangiogenesis expand across the olfactory mucosa. Further studies are needed to elucidate the underlying molecular mechanisms and to determine the functional relevance of olfactory lymphangiogenesis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101119"},"PeriodicalIF":3.5,"publicationDate":"2025-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268833","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":"Assessing the neuroendocrine and psychological effects of acute everolimus administration in healthy male participants","authors":"Lucie Jacquet ,&nbsp;Anna Lena Friedel ,&nbsp;Elisa Orth ,&nbsp;Nathalie Reiser ,&nbsp;Tina Hörbelt-Grünheidt ,&nbsp;Sophie Wiczoreck ,&nbsp;Oliver Witzke ,&nbsp;Manfred Schedlowski ,&nbsp;Marie Jakobs","doi":"10.1016/j.bbih.2025.101120","DOIUrl":"10.1016/j.bbih.2025.101120","url":null,"abstract":"<div><div>Previous experimental studies have shown that immunosuppressive mechanistic target of rapamycin inhibitors can induce neuropsychological changes, such as anxiety and depression, in healthy rodents. Furthermore, psychiatric conditions including anxiety have been reported in transplant patients and healthy subjects receiving the mechanistic target of rapamycin inhibitor everolimus. Thus, the present study aimed to further investigate the potentially dose-dependent neuroendocrine and psychological adverse side effects of acute everolimus intake in healthy male subjects. To this end, P70S6 kinase and Akt expression and phosphorylation in peripheral mononuclear blood cells as well as plasma and saliva cortisol, plasma noradrenaline and plasma dehydroepiandrosterone sulfate have been evaluated via western blotting and ELISA. State anxiety and depression have been assessed using questionnaires. Administering 2.5 mg of everolimus four times significantly increased blood peak levels. Additionally, acute everolimus intake led to decreased P70S6 kinase and slightly increased Akt phosphorylation, while protein expression remained unregulated. However, no effects on neuroendocrine parameters including cortisol, noradrenaline and dehydroepiandrosterone sulfate have been reported. Consistent with these findings, acute everolimus administration had no impact on psychological parameters, such as anxiety and depression. Overall, the present study demonstrated that the acute administration of 2.5 mg everolimus in healthy men does not lead to neuroendocrine or psychological adverse side effects. However, as other studies have reported neuroendocrine alterations as well as anxiety- and depression-like symptoms at lower everolimus doses, these findings should be further verified to determine whether everolimus induces psychiatric side effects in a dose-dependent manner.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101120"},"PeriodicalIF":3.5,"publicationDate":"2025-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268333","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":"Inverted “u-shaped” association of cold-water immersion frequency with mental health and upper respiratory tract infection: a cross-sectional study","authors":"Jan Czarnecki ,&nbsp;Łukasz Mokros","doi":"10.1016/j.bbih.2025.101118","DOIUrl":"10.1016/j.bbih.2025.101118","url":null,"abstract":"<div><h3>Introduction</h3><div>Evidence for a link between cold-water immersion (CWI) and health benefits remains scarce. The aim of this study was to verify whether CWI and its frequency is associated with mental health indices, duration of upper respiratory tract infection (URTI) and duration of sick leave (SL) taken due to URTI.</div></div><div><h3>Methods</h3><div>Data on N = 732 polar plungers and N = 501 controls was collected via the Internet in June 2022. The following self-reported methods were included: 28-item General Health Questionnaire (GHQ-28) comprising four subscales (somatic symptoms, anxiety and insomnia, social dysfunction, and depressive symptoms), URTI and SL durations were represented as a number of days. The statistical analysis involved analysis of covariance and linear regression controlled for confounding variables: sex, age, multimorbidity, temperament and mindfulness.</div></div><div><h3>Results</h3><div>Polar plungers declared better mental health status, shorter URTIs and SLs. The increase in frequency of CWI up to twice per week was associated with a decrease in general mental health index (effect size sR = −0.164), shortening of URTIs (sR = −0.144), and SLs (sR = −0.145). Further increase in the frequency was linked to worsening of the results. CWIs twice per week were related to the shortest URTIs (B = −4.431, p &lt; 0.001), shortest SLs (B = −2.606, p &lt; 0.001), and lowest depressive symptoms score (B = −1.057, p &lt; 0.001).</div></div><div><h3>Conclusion</h3><div>Regular performance of CWI may be related to better mental health, and immunity against URTI in a dose-related manner. These relationships resembled an inverted u-shaped curve and were independent of confounding parameters. Further studies are required to determine whether CWI could be a cost-effective health intervention.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101118"},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268834","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":"Break free from cognitive impairment: The magic of exercise-induced molecules","authors":"Wenbo Liu ,&nbsp;Hui Zhang ,&nbsp;Qiuting Zeng ,&nbsp;Wenlan Cai ,&nbsp;Yunfeng Rui ,&nbsp;Jie Sun","doi":"10.1016/j.bbih.2025.101117","DOIUrl":"10.1016/j.bbih.2025.101117","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101117"},"PeriodicalIF":3.5,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268836","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":"Blood diagnostic biomarkers for neurologic manifestations of long COVID","authors":"A.S. Padhye ,&nbsp;I.J. Koralnik ,&nbsp;B.A. Hanson ,&nbsp;L. Visvabharathy ,&nbsp;R.K. DeLisle ,&nbsp;G. Tachas","doi":"10.1016/j.bbih.2025.101110","DOIUrl":"10.1016/j.bbih.2025.101110","url":null,"abstract":"<div><h3>Background</h3><div>SARS-CoV-2 responsible for COVID-19 caused a global pandemic, with billions of infections, millions of deaths and ongoing manifestations post COVID-19. “Long Covid”, a Post-Acute Sequelae of COVID-19 (PASC), is an ongoing global healthcare problem, affecting all age groups, with many manifestations, and occurring despite vaccines and antivirals. Neurologic manifestations of PASC (Neuro-PASC) such as brain fog can last for years and are amongst the most debilitating and prevalent. There is a need for diagnostic tools and treatments.</div></div><div><h3>Methods</h3><div>Plasma samples from 48 non-hospitalized PASC patients with diagnosed Neuro-PASC symptoms (NP), 20 convalescent control (CC) subjects, and 24 unvaccinated healthy control (HC) subjects, was used to generate data on over 7000 proteins using the SomaLogic® proteomics platform. ProViz® software was used to perform T-tests, U-Tests, ANOVA and Kruskalis-Wallis tests at a Bonferroni p &lt; 0.05 and a Benjamini-Hochberg corrected False Discovery Rate &lt;0.02, and box plots and knowhow used to identify diagnostic biomarkers and therapeutic targets.</div></div><div><h3>Results</h3><div>C5a, TGFβ1, and Gliomedin, used together differentiated patients with Neuro-PASC from control subjects with 94 % sensitivity and 86 % specificity, a 90 % accuracy. Additional biomarkers, Gal3ST1, IFNλ1, and GHRH, improved accuracy to 94 %, and a combination of 5 more biomarkers, LFA-3, FASLG + Transgelin-1 and GPNMB + IGHG1, improved accuracy close to 100 %. These markers are suggestive of pathways involved in Neuro-PASC pathogenesis. A dozen partly overlying biomarkers were modulated to which there are FDA approved drugs.</div></div><div><h3>Conclusion</h3><div>C5a, TGFβ1, Gliomedin expressed highly in serum could be developed as a diagnostic tool, and with clinical assessment used to personalize treatments with repurposed novel drugs.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101110"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145325427","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":"Astroglia-mediated neuroinflammation as a putative mechanism of neurological outcomes in COVID-19? Insights from a Brazilian cohort","authors":"Ethiane Segabinazi ,&nbsp;Fernando R. Tocantins ,&nbsp;Talita Glaser ,&nbsp;Tamires Maglio ,&nbsp;Nathalia C. Oliveira ,&nbsp;Andrelissa Gorete Castanha ,&nbsp;Fabiele Baldino Russo ,&nbsp;Paulo Emílio Corrêa Leite ,&nbsp;Anita Brito ,&nbsp;Camila Vieira Molina ,&nbsp;Gabriela Prado Paludo ,&nbsp;Raquel de Oliveira Souza ,&nbsp;Simone Ravena Maia Alves ,&nbsp;Marielton dos Passos Cunha ,&nbsp;Henning Ulrich ,&nbsp;Edison Luiz Durigon ,&nbsp;Paola Minoprio ,&nbsp;Patricia C.B. Beltrão-Braga","doi":"10.1016/j.bbih.2025.101115","DOIUrl":"10.1016/j.bbih.2025.101115","url":null,"abstract":"<div><div>NeuroCOVID-19 has emerged as a significant global health concern, presenting a wide spectrum of neurological manifestations, including headaches, brain fog and anosmia. While mounting evidence indicates that SARS-CoV-2 infection compromises central nervous system (CNS) function, the precise processes underlying these effects remain incompletely understood. Although neurons have been extensively studied, astrocytes – critical regulators of brain homeostasis - have been largely overlooked in this context. In this study, we position astrocytes as central players in the neuropathological landscape of neuroCOVID-19, challenging their traditionally supportive role. We evaluated the frequent neurological symptoms in a Brazilian cohort of COVID-19 patients and investigated whether SARS-CoV-2 infection of cortical astrocytes induces neuroinflammation, glutamatergic imbalance, vasoregulatory disruption, and apoptosis as likely pathogenic processes. Among 162 COVID-19-positive patients, headache (53.09 %), brain fog (42.15 %), and anosmia (38.72 %) were the most commonly reported symptoms. Using human-induced pluripotent stem cell (hiPSC)-derived astrocytes, we found that SARS-CoV-2 infection promotes a pronounced pro-inflammatory response, evidenced by elevated levels of IL-6, IL-15, and IL-4 in the culture supernatant. Infected astrocytes also showed reduced mRNA expression of <em>KLK1</em> and <em>EAAT1</em>, key genes involved in vasodilation and glutamate clearance, respectively. Additionally, a significant increase in cleaved caspase-3-positive cells indicated enhanced apoptosis. Overall, these findings demonstrate that SARS-CoV-2 disrupts astrocyte homeostatic functions, leading to neuroinflammation, excitatory neurotransmission dysregulation, and cell death that may, hypothetically, underlie the neurological sequelae of COVID-19. By reframing astrocytes as active protagonists, this study highlights their essential role in CNS vulnerability. It also suggests potential targets for the future investigation in the development of therapies against the neurological complications of COVID-19.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"49 ","pages":"Article 101115"},"PeriodicalIF":3.5,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145268332","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}