Brain, Behavior, and Immunity最新文献

{"title":"Role of early life adversities in inflammation-related neuropsychiatric comorbidity in obesity","authors":"Juliette Montet ,&nbsp;Sandra Dexpert ,&nbsp;Muriel Darnaudéry ,&nbsp;Cédric Beau ,&nbsp;Damien Forestier ,&nbsp;Patrick Ledaguenel ,&nbsp;Eric Magne ,&nbsp;Bruno Aouizerate ,&nbsp;Lucile Capuron","doi":"10.1016/j.bbi.2025.04.039","DOIUrl":"10.1016/j.bbi.2025.04.039","url":null,"abstract":"<div><div>A growing body of data highlights the key role of adiposity-related inflammation in the development of neuropsychiatric comorbidity in obesity. Nevertheless, despite similar levels of inflammation, only a subgroup of obese subjects is afflicted with neuropsychiatric symptoms, suggesting the contribution of additional vulnerability factors. In light of previous work suggesting the involvement of early life adversity (ELA), this study aims to determine whether ELA promotes the emergence of inflammation-related neuropsychiatric symptoms in a sample of obese subjects.</div><div>Eighty-two adults afflicted with obesity (BMI &gt; 30 kg/m²) and twenty-one lean individuals (BMI &lt; 25 kg/m²) were recruited. Depressive symptoms, fatigue and neurobehavioral symptoms were assessed through semi-structured interviews and validated self-reports. ELA was measured using the Childhood Trauma Questionnaire (CTQ). Systemic inflammation was determined through serum concentrations of high-sensitivity C-reactive protein (hsCRP).</div><div>In the whole population under study, hsCRP concentrations were significantly associated with neuropsychiatric symptoms, consistent with the increased prevalence of neuropsychiatric comorbidity in obese subjects. Significant associations were also found between ELA severity and neuropsychiatric symptoms. Although they did not influence hsCRP levels, ELA antecedents in obese subjects were associated with more marked mood, fatigue and cognitive symptoms. Among ELA, sexual abuse was the only significant predictor of the association between hsCRP levels and neuropsychiatric comorbidity in obesity. These findings support the hypothesis that ELA represents a potent vulnerability factor for the development of neuropsychiatric comorbidity in obese subjects with chronic inflammation.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 612-619"},"PeriodicalIF":8.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143912606","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":"PACAP a mediator of inflammation following trauma exposure and mild traumatic brain injury: Differential effects in males and females","authors":"Shane W. Adams ,&nbsp;Aoife O’Donovan ,&nbsp;Thomas C. Neylan ,&nbsp;Victor May ,&nbsp;Sayamwong E. Hammack ,&nbsp;Kerry Ressler ,&nbsp;Odette A. Harris ,&nbsp;Sabra S. Inslicht","doi":"10.1016/j.bbi.2025.04.038","DOIUrl":"10.1016/j.bbi.2025.04.038","url":null,"abstract":"<div><div>Individual differences in systemic responses to trauma exposure, posttraumatic stress disorder (PTSD), and/or mild traumatic brain injury (mTBI) may help account for differential risk of adverse sequalae in females and heterogeneity in pathophysiology, symptoms, and treatment responses. Accordingly, this study investigated sex differences in the association between neuroendocrine (pituitary adenylate cyclase-activating polypeptide [PACAP]) and inflammatory markers following lifespan trauma exposure, PTSD, and mTBI in 71 trauma-exposed veteran and non-veteran males (<em>n</em> = 41) and females (<em>n</em> = 30). Two mediation models were proposed and evaluated, informed by an existing theoretical model. Both mediation models examined elevated PACAP as a key variable that may be associated with elevated inflammatory cytokine interleukin-6 (IL-6). The first model evaluated this effect following psychological trauma exposure and the second following mTBI. Trauma exposure and mTBI accounted for a large proportion of sex differences in PACAP and inflammation independent of the effects of time since the events (<em>M</em> = 8–11 years), PTSD symptom severity and diagnostic status, suggesting potentially long-term impacts of trauma exposure and mTBI on systemic pathophysiological responses regardless of PTSD symptom variations. Specifically, PACAP mediated the relationship between cumulative trauma exposure and IL-6 as well as mTBI history and IL-6, with a stronger mediating effect of PACAP on mTBI (<em>β</em> = 0.352) than trauma exposure (<em>β</em> = 0.149). Sex differences were observed in which males with mTBI histories had significantly elevated PACAP levels (Hedges’ g = 0.79) and females with mTBI histories had significantly elevated IL-6 levels (Hedges’ g = 1.03). PACAP was uniquely associated with trauma exposure in females (<em>β</em> = 0.56) and mTBI in males (<em>β</em> = 0.35). Conversely, IL-6 was uniquely associated with mTBI in females (<em>β</em> = 0.47–0.61) and trauma exposure in males (<em>β</em> = 0.42–0.54). For both sexes, childhood emotional neglect was uniquely associated with PACAP and inflammation later in life. This study presents preliminary evidence of the association between PACAP and inflammation following both trauma exposure and mTBI, which was differentially related in males and females. Although further study is needed, findings have the potential to help explicate heterogeneous presentations and differential risk of trauma-related pathology and mTBI that could lead to more targeted and effective treatments.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 589-599"},"PeriodicalIF":8.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899941","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":"Exercise-induced β2-adrenergic receptor activation enhances effector lymphocyte mobilization in humans and suppresses lymphoma growth in mice through NK-cells","authors":"Kyle A. Smith ,&nbsp;Helena Batatinha ,&nbsp;Grace M. Niemiro ,&nbsp;Forrest L. Baker ,&nbsp;Tiffany M. Zúñiga ,&nbsp;Douglass M. Diak ,&nbsp;Preteesh L. Mylabathula ,&nbsp;Timothy M. Kistner ,&nbsp;Dan Davini ,&nbsp;Emely Hoffman ,&nbsp;Jamie N. Colombo ,&nbsp;Michael D. Seckeler ,&nbsp;Richard A. Bond ,&nbsp;Emmanuel Katsanis ,&nbsp;Richard J. Simpson","doi":"10.1016/j.bbi.2025.04.040","DOIUrl":"10.1016/j.bbi.2025.04.040","url":null,"abstract":"<div><div>Signaling through the β₂-adrenergic receptor (β2-AR) mobilizes immune cells during exercise and is implicated in tumor lymphocyte infiltration. We investigated mechanisms governing immune cell mobilization in humans and the role of adrenergic signaling in anti-cancer responses to a murine lymphoma. Human studies included double-blind, placebo-controlled, crossover trials with beta blocker drugs and a phosphodiesterase inhibitor during steady-state and graded exercise, and a synthetic β agonist (isoproterenol) infusion model. β₁ + β₂-AR blockade reduced lymphocyte and NK-cell mobilization during steady-state exercise, while β₁-AR blockade enhanced the mobilization of NK-cells. Combining a β₁-AR antagonist with a phosphodiesterase-4 (PDE4) inhibitor during graded exercise further increased mobilization of CD8 + T-cells, γδ T-cells, and monocytes. Isoproterenol infusion also elevated lymphocyte and NK-cell levels similarly to exercise at 70 % VO_2max. Single cell RNA sequencing revealed complex signaling downstream of cAMP that relate to lymphocyte activation and effector function. In murine models of voluntary wheel running, β₂-AR signaling and NK-cells were critical for exercise-induced protection against B-cell lymphoma, as β₂-AR blockade or NK-cell depletion abrogated these effects. These findings highlight the pivotal role of β₂-AR signaling in mobilizing cytotoxic immune cells and protecting against tumor progression through exercise, suggesting potential therapeutic strategies combining exercise with adrenergic modulation to enhance immune responses.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 751-765"},"PeriodicalIF":8.8,"publicationDate":"2025-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143966739","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 immune system: An effective therapeutic target for duloxetine","authors":"Nathalie Castanon","doi":"10.1016/j.bbi.2025.04.035","DOIUrl":"10.1016/j.bbi.2025.04.035","url":null,"abstract":"","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 510-511"},"PeriodicalIF":8.8,"publicationDate":"2025-04-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886586","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":"Beneficial and adverse effects of THC on cognition in the HIV-1 transgenic rat model: Importance of exploring task- and sex-dependent outcomes","authors":"Samantha M. Ayoub ,&nbsp;Sunitha Vemuri ,&nbsp;Elizabeth B. Hoang ,&nbsp;Neal A. Jha ,&nbsp;Arpi Minassian ,&nbsp;Jared W. Young","doi":"10.1016/j.bbi.2025.04.030","DOIUrl":"10.1016/j.bbi.2025.04.030","url":null,"abstract":"<div><div>HIV-associated neurocognitive impairment (NCI) is an untreated concern among people living with HIV (PLWH). Cannabis use in PLWH may complicate outcomes on cognition, with evidence to suggest function-dependent effects that are modulated by several factors including use patterns (e.g., frequency of use) and demographic influences (e.g., age). Animal studies can control for these factors.</div><div>Here, we characterized the impact of the primary psychoactive ingredient in cannabis (delta-9-tetrahydrocannabinol; THC), on function-dependent cognitive outcomes in HIV-1 transgenic (Tg) rats using cross-species translatable assays. Female and male HIV-1Tg rats and their controls were tested in the rat Iowa Gambling Task (IGT; to measure risk-based decision-making), and the Probabilistic Reversal Learning Task (PRLT; to measure learning and cognitive flexibility). Rats were tested at baseline, then retested following acute and chronic exposures to THC (0, 0.3, 3 mg/kg, intraperitoneal injection).</div><div>At baseline, HIV-1Tg rats took longer to make decisions, but exhibited intact cognition across tasks, suggestive of a speed-accuracy trade-off and early cognitive deficits. Both acute and chronic THC exposures produced selective effects on primary performance measures in HIV-1Tg rats, including enhanced learning performance but worsened risk-based decision-making, not observed in controls.</div><div>This work confirms function-dependent effects of THC on cognitive function in an animal model of HIV using cross-species translatable tasks used in the clinic. Findings are consistent with evidence for function-dependent cannabis effects observed in HIV, and suggest THC may drive cannabis-induced changes observed on cognitive performance in PLWH. These data may serve as guidance for clinicians prescribing cannabis to patients with HIV, and for further research exploring the interactive effects of HIV and cannabinoid treatment on cognitive function.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 571-588"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143899940","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":"Decreased excitatory and increased inhibitory transmission in the hippocampal CA1 drive neuroinflammation-induced cognitive impairments in mice","authors":"Xin-miao Wu ,&nbsp;Cui-na Shi ,&nbsp;Kai Liu ,&nbsp;Xiao-yi Hu ,&nbsp;Qiu-li He ,&nbsp;Hao Yao ,&nbsp;Di Fan ,&nbsp;Da-qing Ma ,&nbsp;Jian-jun Yang ,&nbsp;Jin-chun Shen ,&nbsp;Mu-huo Ji","doi":"10.1016/j.bbi.2025.04.027","DOIUrl":"10.1016/j.bbi.2025.04.027","url":null,"abstract":"<div><div>Neuroinflammation is one of crucial pathogenic mechanisms underlying Alzheimer’s disease, sepsis-associated encephalopathy, and postoperative cognitive dysfunction. These diseases or conditions are often accompanied by typical clinical manifestations of cognitive impairments, including impaired learning and memory but underlying mechanisms are unknown. Hence, effective treatments are not available. In the current study, mice received intraperitoneal administrations of LPS (0.5 mg/kg, daily, Escherichia coli<!--> <!-->O55:B5) for seven consecutive days and after which, different cohorts were used for behavioral assessments with open field, Y maze, and novel object recognition test or for electrophysiology recordings of mEPSC, mIPSC or LTP in <em>ex vivo</em> preparations. Their hippocampi were harvested for immunostaining or Western blotting of PSD95, vGLUT1, vGAT, gephyrin, PV, and SST. <em>In vivo</em> optical fiber calcium recording was used to evaluate the neuronal excitability. During the early stage of neuroinflammation induced by LPS, there was a decrease of excitatory afferent synapses and transmission in the CA1. During the later stage of neuroinflammation, there was an increase of inhibitory afferent synapses and transmission in the CA1, resulting in excessive inhibition on excitatory neurons. Both of them contributed to the decreased hippocampal neuronal excitability and impaired LTP, ultimately leading to cognitive impairments. Overexpression of CREB in the early stage or inactivation of PV-positive interneurons in the later stage in the CA1 both improved cognitive impairments. Our work suggests that negating decreased excitatory and increased inhibitory afferent in the hippocampus may improve cognitive impairments relate to neuroinflammation associated with neurological diseases.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 416-428"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874411","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":"Cell-type-specific and inflammatory DNA methylation patterns associated with PTSD","authors":"Alicia K. Smith ,&nbsp;Seyma Katrinli ,&nbsp;Adam X. Maihofer ,&nbsp;Allison E. Aiello ,&nbsp;Dewleen G. Baker ,&nbsp;Marco P. Boks ,&nbsp;Leslie A. Brick ,&nbsp;Chia-Yen Chen ,&nbsp;Shareefa Dalvie ,&nbsp;Negar Fani ,&nbsp;Catherine B. Fortier ,&nbsp;Joel Gelernter ,&nbsp;Elbert Geuze ,&nbsp;Charles F. Gillespie ,&nbsp;Jasmeet P. Hayes ,&nbsp;Suzi Hong ,&nbsp;Ronald C. Kessler ,&nbsp;Anthony P. King ,&nbsp;Nastassja Koen ,&nbsp;Karestan C. Koenen ,&nbsp;Anthony S. Zannas","doi":"10.1016/j.bbi.2025.04.031","DOIUrl":"10.1016/j.bbi.2025.04.031","url":null,"abstract":"<div><h3>Background</h3><div>Epigenetic modifications, including DNA methylation (DNAm), can change in response to traumatic stress exposure, and may help to distinguish between individuals with and without PTSD. Here, we examine the DNAm patterns specific to immune cell types and inflammation in those with PTSD.</div></div><div><h3>Methods</h3><div>This study includes 3,277 participants from 11 cohorts participating in the Psychiatric Genomics Consortium (PGC) PTSD Epigenetics Workgroup. DNAm was assayed from blood with the MethylationEPIC BeadChip. A standardized QC pipeline was applied and used to impute cell composition. Within each cohort, we identified cell-type-specific DNAm patterns associated with PTSD, controlling for sex (if applicable), age, and ancestry. Meta-analyses were performed from summary statistics.</div></div><div><h3>Results</h3><div>PTSD cases had lower proportions of B cells and NK cells as well as higher proportions of neutrophils when compared to trauma-exposed controls. Overall, we identified 96 PTSD-associated CpGs across six types of immune cells. Most of these differences were identified in B cells, with 95 % exhibiting lower methylation levels in those with PTSD. Interestingly, the PTSD-associated CpGs annotated to a gene in B cells were enriched in a recent GWAS of PTSD (p &lt; 0.0001).</div></div><div><h3>Conclusions</h3><div>This study identifies novel PTSD-associated CpGs in individual immune cell types and supports the role of immune dysregulation and inflammation in PTSD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 540-548"},"PeriodicalIF":8.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886469","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":"Peripheral-central immune crosstalk in Parkinson’s disease and its association with clinical severity","authors":"Julia C. Greenland ,&nbsp;Jonathan Holbrook ,&nbsp;Lakmini Kahanawita ,&nbsp;Marta Camacho ,&nbsp;Tim D. Fryer ,&nbsp;Young T. Hong ,&nbsp;Caroline H. Williams-Gray","doi":"10.1016/j.bbi.2025.04.028","DOIUrl":"10.1016/j.bbi.2025.04.028","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Increasingly, the immune system is implicated in the aetiology and progression of Parkinson’s disease (PD). Immune activation is seen both peripherally in the blood, with a tendency towards a pro-inflammatory profile, and centrally in the cerebrospinal fluid and brain parenchyma, with microglial activation and increased numbers of immune cells in the central nervous system. However, the relationship between this peripheral and central immune profile, as well as the association with clinical measures of disease severity is not clear.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;61 people with PD, within three years of diagnosis and no immune comorbidities, and 51 matched controls underwent detailed blood immunophenotyping using a flow cytometry panel with markers to characterise adaptive and innate immune populations. In the PD cohort, 35 also had cerebrospinal fluid (CSF) immune cell analysis and 31 underwent positron emission tomography (PET) brain imaging with the radioligand [&lt;sup&gt;11&lt;/sup&gt;C]-PK11195 to assess microglial activation. PD participants were assessed with the Movement Disorder Society-Unified Parkinson’s disease rating Scale (MDS-UPDRS) and the Addenbrooke’s Cognitive Examination (ACE-III). The immune profiles of PD and control participants were compared. In the PD group, relationships between peripheral and CSF immune cell populations, [&lt;sup&gt;11&lt;/sup&gt;C]-PK11195 binding, and clinical measures were investigated in exploratory analyses using multiple linear regression.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;Compared to controls, PD participants had a pro-inflammatory profile in the blood with an elevated Systemic Inflammatory Index (SII) (&lt;em&gt;p&lt;/em&gt; = 0.049), a higher percentage of classical monocytes (&lt;em&gt;p =&lt;/em&gt; 0.046), and decreased expression of functional markers of T regulatory cells (FoxP3 (&lt;em&gt;p =&lt;/em&gt; 0.030) and Helios (&lt;em&gt;p =&lt;/em&gt; 0.015)) and B regulatory cells (CD1d (&lt;em&gt;p =&lt;/em&gt; 0.031)).&lt;/div&gt;&lt;div&gt;Immune cell subset numbers in blood and CSF were correlated for CD8+ cells (rho = 0.42, &lt;em&gt;p&lt;/em&gt; = 0.011), CD16+ NK cells (rho = 0.49, &lt;em&gt;p&lt;/em&gt; = 0.004) and classical monocytes (rho = −0.38, &lt;em&gt;p&lt;/em&gt; = 0.028). CSF immune populations were also correlated with [&lt;sup&gt;11&lt;/sup&gt;C]-PK11195 binding in disease-relevant regions of interest.&lt;/div&gt;&lt;div&gt;Several blood and CSF immune cell subsets and regional [&lt;sup&gt;11&lt;/sup&gt;C]-PK11195 binding showed relationships with motor and cognitive scores, with a consistent trend of pro-inflammatory markers being related to a more severe disease phenotype. Increased Toll-like receptor 2 expression on classical monocytes in the CSF and [&lt;sup&gt;11&lt;/sup&gt;C]-PK11195 binding in the substantia nigra independently predicted motor score (MDS-UPDRS-III).&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;This exploratory study suggests that peripheral and central immune changes are closely linked in PD, and relevant to clinical disease severity. These findings warrant further validation and exploration ","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 558-570"},"PeriodicalIF":8.8,"publicationDate":"2025-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143894899","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":"I see sick people: Beliefs about sensory detection of infectious disease are largely consistent across cultures","authors":"Joshua M. Ackerman ,&nbsp;Theodore Samore ,&nbsp;Daniel M.T. Fessler ,&nbsp;Tom R. Kupfer ,&nbsp;Soyeon Choi ,&nbsp;Wilson N. Merrell ,&nbsp;Lene Aarøe ,&nbsp;Toivo Aavik ,&nbsp;Stephen Acabado ,&nbsp;Grace Akello ,&nbsp;Ilham N. Alfian ,&nbsp;Laith Al-Shawaf ,&nbsp;Marinés M. Alvarez ,&nbsp;Jeanine Ammann ,&nbsp;Gizem Arikan ,&nbsp;Saiyeda A. Asha ,&nbsp;Anibal M. Astobiza ,&nbsp;Carmen G. Baeza-Ugarte ,&nbsp;Pat Barclay ,&nbsp;Fiona Kate Barlow ,&nbsp;Iris Žeželj","doi":"10.1016/j.bbi.2025.04.020","DOIUrl":"10.1016/j.bbi.2025.04.020","url":null,"abstract":"<div><div>Identifying cues to contagious disease is critical for effectively tracking and defending against interpersonal infection threats. People hold lay beliefs about the types of sensory information most relevant for identifying whether others are sick with transmissible illnesses. Are these beliefs universal, or do they vary along cultural and ecological dimensions? Participants in 58 countries (N = 19,217) judged how effective, and how likely they were to use, cues involving each of the five major sensory modalities in an imagined social interaction during a flu outbreak. Belief patterns were strongly consistent across countries (sight &gt; audition &gt; touch &gt; smell &gt; taste), suggesting a largely universal conceptualization of the role of sensory information for interpersonal respiratory disease detection. Results also support a safe senses hypothesis, with perceivers reporting that they would use senses that function at a distance—and thus reduce pathogen transmission risk—more than would be expected given participants’ beliefs as to the efficacy of these senses for disease detection. Where societal variation did emerge, it was captured by a cohesive set of socio-ecological factors, including human development, latitude, pathogen prevalence, and population density. Together, these findings reveal a shared lens through which contagious respiratory disease is assessed, one that prioritizes minimizing risk to perceivers, and may offer leverage for designing interventions to improve public health.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 737-750"},"PeriodicalIF":8.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143953885","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":"SOAT1 dysregulation in astrocytes drives Blood–Brain barrier dysfunction and neuroinflammation in Alzheimer’s disease","authors":"Lian Huang ,&nbsp;Fu Zeng ,&nbsp;Hui Wei ,&nbsp;Tong Su ,&nbsp;Yuwen Su ,&nbsp;Yarong Lin ,&nbsp;Qi Niu ,&nbsp;Qi Xu","doi":"10.1016/j.bbi.2025.04.032","DOIUrl":"10.1016/j.bbi.2025.04.032","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a neurodegenerative disorder that leads to memory loss and cognitive decline, in which blood–brain barrier (BBB) and astrocyte dysfunction are significantly involved. Recent evidence suggests that dysregulation of lipid metabolism in astrocytes contributes to BBB disruption and neuroinflammation in AD. Sterol O-acyltransferase 1 (SOAT1), an enzyme involved in cholesterol esterification, has been implicated in BBB disruption and neuroinflammation, but its specific role in AD remains unclear. This study aimed to investigate the impact of SOAT1 on lipid metabolism, BBB integrity, and neuroinflammation in AD. Using Oil Red O staining of human autopsy brain tissue and reanalysis of publicly available single-nucleus RNA sequencing (snRNA-seq) data, we identified a significant increase in lipid droplet accumulation and lipid metabolism gene expression, particularly in astrocytes, in the brains of AD patients. Furthermore, in vitro BBB models and the 5 × FAD mouse model were used to explore how SOAT1 expression influences BBB function. Our results demonstrated that elevated SOAT1 expression in astrocytes was positively correlated with increased lipid droplet accumulation and compromised BBB integrity. Knockdown of SOAT1 using siRNA or treatment with the SOAT1 inhibitor K604 restored BBB function, reduced neuroinflammation, and improved cognitive function in 5 × FAD mice. These findings suggest that SOAT1 plays a critical role in astrocytic lipid metabolism and BBB dysfunction in AD. Targeting SOAT1 may be a promising therapeutic approach to alleviate neuroinflammation and restore cognitive function in AD patients.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 497-509"},"PeriodicalIF":8.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886466","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}