Brain, Behavior, and Immunity最新文献

{"title":"Peripheral-central immune crosstalk in Parkinson’s disease and its association with clinical severity","authors":"Julia C. Greenland , Jonathan Holbrook , Lakmini Kahanawita , Marta Camacho , Tim D. Fryer , Young T. Hong , Caroline H. Williams-Gray","doi":"10.1016/j.bbi.2025.04.028","DOIUrl":"10.1016/j.bbi.2025.04.028","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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 [<sup>11</sup>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, [<sup>11</sup>C]-PK11195 binding, and clinical measures were investigated in exploratory analyses using multiple linear regression.</div></div><div><h3>Results</h3><div>Compared to controls, PD participants had a pro-inflammatory profile in the blood with an elevated Systemic Inflammatory Index (SII) (<em>p</em> = 0.049), a higher percentage of classical monocytes (<em>p =</em> 0.046), and decreased expression of functional markers of T regulatory cells (FoxP3 (<em>p =</em> 0.030) and Helios (<em>p =</em> 0.015)) and B regulatory cells (CD1d (<em>p =</em> 0.031)).</div><div>Immune cell subset numbers in blood and CSF were correlated for CD8+ cells (rho = 0.42, <em>p</em> = 0.011), CD16+ NK cells (rho = 0.49, <em>p</em> = 0.004) and classical monocytes (rho = −0.38, <em>p</em> = 0.028). CSF immune populations were also correlated with [<sup>11</sup>C]-PK11195 binding in disease-relevant regions of interest.</div><div>Several blood and CSF immune cell subsets and regional [<sup>11</sup>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 [<sup>11</sup>C]-PK11195 binding in the substantia nigra independently predicted motor score (MDS-UPDRS-III).</div></div><div><h3>Conclusion</h3><div>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, Theodore Samore, Daniel M T Fessler, Tom R Kupfer, Soyeon Choi, Wilson N Merrell, Lene Aarøe, Toivo Aavik, Stephen Acabado, Grace Akello, Ilham N Alfian, Laith Al-Shawaf, Marinés M Alvarez, Jeanine Ammann, Gizem Arikan, Saiyeda A Asha, Anibal M Astobiza, Pat Barclay, Fiona Kate Barlow, Lisiane Bizarro, Paola Bressan, Andres Castellanos-Chacón, Bryan K C Choy, Achmad Chusairi, Brenda L Chávez Cosamalón, Jorge Contreras-Garduño, Mallika De, Tiago J S de Lima, Angelica N Oliveira, Piyanjali de Zoysa, Ieva Dryžaitė, Christian T Elbæk, Peter Fedor, Ana M Fernández, Márta Fülöp, Vladimer Lado Gamsakhurdia, Leonor Garcia-Gómez, Leonel Garcia-Marques, Jimena Garduño-Franco, María Del Pilar Grazioso, Fanny Habacht, Youssef Hasan, Camila P Haugestad, Christian P Haugestad, Jan Havlíček, Earl J Hernandez, Vu M Hoang, Minsung Hong, Ivana Hromatko, Dzintra Iliško, Hirotaka Imada, Ivana Jakšić, Tomasz Jarmakowski, Harpa L Hjördísar Jónsdóttir, Kotrina Kajokaite, Šárka Kaňková, Nicolas Kervyn, Jinseok P Kim, Jonas R Kunst, Michael Laakasuo, Juan David Leongómez, Norman Li, Junsong Lu, Nathan Lynch, María A Maegli, Harry Manley, Gabriela Marcu, Thea McAfee, Panagiotis Mitkidis, Regina Fernandez-Morales, Coby Morvinski, Haslina Muhamad, Molnár B Nándor, Pegah Nejat, Bernardo Costa-Neves, Hoang Nguyen Huy, Mats J Olsson, Charity N Onyishi, Ike E Onyishi, Reegan Orozco, Tobias Otterbring, Ida S Ottersen, Gustavo Pacheco-López, Penny Panagiotopoulou, Walter Paniagua, Roksana Parvin, Zoran Pavlović, Pavol Prokop, Emma Raffman, Muhammad Rizwan, Sheila Rojas, Joanna Różycka-Tran, Oscar R Sánchez, Heyla Selim, Barış Sevi, Yaniv Shani, Madhulika S Shastry, Stefan Stieger, Eunkook M Suh, Melati Sumari, Kosuke Takemura, Arnaud Tognetti, Joshua Tybur, Eylul B Ucak, Yukiko Uchida, Carmen G Baeza-Ugarte, Jaroslava V Valentova, Hugo Viciana, Amandine Visine, Jin Wang, X T Wang, Illia I Yahiiaiev, Roberta Z R Trombetta, Rizqy A Zein, Iris Žeželj","doi":"10.1016/j.bbi.2025.04.020","DOIUrl":"https://doi.org/10.1016/j.bbi.2025.04.020","url":null,"abstract":"<p><p>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 > audition > touch > smell > 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.</p>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":" ","pages":""},"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}

{"title":"Microglia endotoxin tolerance is retained after enforced repopulation","authors":"Tiago Medeiros-Furquim,&nbsp;Anneke Miedema,&nbsp;Edwin Schilder,&nbsp;Nieske Brouwer,&nbsp;Inge R. Holtman,&nbsp;Susanne M. Kooistra,&nbsp;Bart J.L. Eggen","doi":"10.1016/j.bbi.2025.04.014","DOIUrl":"10.1016/j.bbi.2025.04.014","url":null,"abstract":"<div><div>Microglia are crucial for CNS homeostasis and are involved in a wide range of neurodegenerative and neuroinflammatory diseases. Systemic inflammation and infections can contribute to neurodegeneration later in life by affecting microglia. Like other innate immune cells, microglia can develop innate immune memory (IIM) in response to an inflammatory challenge, altering their response to subsequent stimuli. IIM can ameliorate or worsen CNS pathology, but it is unclear if IIM can be reversed to restore microglia functions. Here, we investigated whether microglia depletion-repopulation by inhibition of the colony-stimulating factor 1 receptor with BLZ945 reversed LPS-induced microglia endotoxin tolerance in mice. Repopulated microglia displayed a reduced expression of homeostatic genes and genes related to mitochondrial respiration and TCA cycle metabolism and an increased expression of immune effector and activation genes. Nonetheless, the blunted inflammatory gene response after LPS-preconditioning was retained after a depletion-repopulation cycle. Our study highlights the persistence of endotoxin tolerance in microglia after a depletion-repopulation cycle, which might impact the potential effectiveness of strategies targeted at microglia depletion for clinical applications.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 512-528"},"PeriodicalIF":8.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886467","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":"SARS-CoV2 vaccination during pregnancy – Vetting the impact on maternal health and long-term consequences for offspring brain function","authors":"Anna Gundacker ,&nbsp;Ron Schaer ,&nbsp;Arnold Pollak ,&nbsp;Ulrike Weber-Stadlbauer ,&nbsp;Daniela D. Pollak","doi":"10.1016/j.bbi.2025.04.029","DOIUrl":"10.1016/j.bbi.2025.04.029","url":null,"abstract":"<div><div>The COVID-19 pandemic has shown the critical importance of vaccination strategies to protect vulnerable populations, including pregnant women, from severe disease and its lingering consequences. Although growing evidence demonstrates that COVID-19 vaccines are both safe and highly beneficial during pregnancy, vaccine hesitancy among pregnant women persists, partly fueled by the persistent, decade-old “urban myth” linking vaccination during pregnancy to neuropsychiatric disorders in children.</div><div>Here we used a mouse model of passive immunization with severe acute respiratory syndrome coronavirus 2 spike neutralizing monoclonal antibodies (SaCoV-AB) to determine the effects of gestational COVID-19 vaccination on key pregnancy outcomes, maternal and offspring health, and behavior.</div><div>We show that at a higher SaCoV-AB dosage, maternal immune response is reflected in elevated TNF-α levels in maternal serum, but not in the placenta or the fetal brain, with no effect on pregnancy outcomes. We report no consequences for postpartum maternal care behavior and neonatal communication signatures. Behavioral assessment of adult female and male offspring after maternal SaCoV-AB treatment revealed no differences in phenotypes relevant to neurodevelopmental disorders.</div><div>Our findings indicate that in a preclinical model, passive immunization with SaCoV-AB during pregnancy is well-tolerated, with no discernable impact on maternal or offspring health and behavior.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 549-557"},"PeriodicalIF":8.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886585","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 basolateral amygdala and striatum propagate alpha-synuclein pathology causing increased fear response in a Parkinson’s disease model","authors":"Thuy Thi Lai ,&nbsp;Wei Xiang ,&nbsp;Milos Stanojlovic ,&nbsp;Christopher Käufer ,&nbsp;Malte Feja ,&nbsp;Kristina Lau ,&nbsp;Friederike Zunke ,&nbsp;Franziska Richter","doi":"10.1016/j.bbi.2025.04.025","DOIUrl":"10.1016/j.bbi.2025.04.025","url":null,"abstract":"<div><div>Alpha-synuclein (aSyn)-related pathology crucially contributes to the pathogenesis of Parkinson’s disease, a frequent and incurable neurodegenerative disease characterized by progressive motor and non-motor symptoms. Anxiety and fear- related neuropsychiatric symptoms develop frequently and early in the disease, but a lack of understanding of pathogenesis hampers rational therapy. This study aimed to decipher whether aSyn pathology in the basolateral amygdala (BLA) is causative of fear and anxiety. Bilateral stereotaxic injections of human aSyn-preformed amyloid fibrils (PFF) in BLA, striatum, or substantia nigra were conducted in female mice overexpressing human aSyn (Thy1-aSyn) and in wildtype littermates (WT). We characterized the propagation of aSyn pathology and related neuropathological changes across brain regions and examined the behavioral and fear responses in mice up to 2 months post-injection of PFF. While PFF injections induced local aSyn fibril pathology close to all respective injection sites in transgenic mice, we observed differences in propagation, downstream pathology and behavioral alterations. The BLA and the striatum, but not the substantia nigra, effectively propagated aSyn pathology to connected brain regions at 2.5 months post injection. This involved enhanced microgliosis and astrogliosis in the nigrostriatal system and loss of GABAergic parvalbuminergic interneurons in the striatum and corticolimbic brain regions. Intra-BLA PFF injections resulted in increased cued fear response in both transgenic mice and WT mice at 1 month post injection. The effect was more pronounced in the transgenic mice. Conversely, intra-striatal PFF injections enhanced contextual fear in WT at 2 months post injection. These findings imply that increased fear is inducible by aSyn pathology, especially if originating in the BLA or striatum. Furthermore, both regions are hub regions of aSyn pathology propagation, thereby contributing to disease progression. These insights provide mechanisms that can guide rational therapeutic development.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 469-486"},"PeriodicalIF":8.8,"publicationDate":"2025-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143878488","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":"Blockage of CCL3 with neutralizing antibody reduces neuroinflammation and reverses Alzheimer disease phenotypes","authors":"Chao Wei ,&nbsp;Jing Liu ,&nbsp;Bing Wu ,&nbsp;Tianhao Shen ,&nbsp;Jiao Fan ,&nbsp;Ye Lin ,&nbsp;Ke Li ,&nbsp;Yane Guo ,&nbsp;Yanchang Shang ,&nbsp;Bo Zhou ,&nbsp;Hengge Xie","doi":"10.1016/j.bbi.2025.04.034","DOIUrl":"10.1016/j.bbi.2025.04.034","url":null,"abstract":"<div><h3>Background</h3><div>Accumulating evidence indicates that neuroinflammation is involved in the pathogenesis of Alzheimer’s disease (AD). According to RNA sequencing and quantitative PCR (qPCR), we found that chemokine CCL3 mRNA expression was abnormally upregulated in the brains of AD transgenic mice. Moreover, the levels of CCL3 in the serum of AD patients were significantly elevated and negatively correlated with their cognitive abilities. However, the role of CCL3 in AD neuroinflammation and pathological damages remains elusive.</div></div><div><h3>Methods</h3><div>Using behavioral, histological, and biochemical methods, outcomes of CCL3 antibody treatment on neuropathology and cognitive deficits were studied in the APPswe/PS1dE9 mice.</div></div><div><h3>Results</h3><div>In the present study, we reported that CCL3 protein expression was increased in the APPswe/PS1dE9 mice, whereas blockage of CCL3 with neutralizing antibody potently inhibited CCL3 activation in the APPswe/PS1dE9 mice down to the levels of wild-type mice. Specifically, CCL3 antibody significantly improved the learning and memory abilities of APPswe/PS1dE9 mice. In addition, CCL3 antibody treatment decreased cerebral amyloid-β (Aβ) levels and plaque burden via inhibiting amyloid precursor protein (APP) processing by reducing beta-site APP cleaving enzyme 1 (BACE1) expression in the APPswe/PS1dE9 mice. We also found that CCL3 antibody treatment alleviated neuroinflammation and reduced synaptic defects in the APPswe/PS1dE9 mice. Furthermore, the activated NF-κB signaling pathway in APPswe/PS1dE9 mice was inhibited by CCL3 antibody treatment.</div></div><div><h3>Conclusions</h3><div>Collectively, our findings provide evidence that CCL3 activation may contribute to the AD pathogenesis and may serve as a novel therapeutic target in the treatment of AD.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 400-415"},"PeriodicalIF":8.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143864098","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":"Recombinant human DNase treatment mitigates extracellular trap mediated damage and improves long-term recovery after spinal cord injury in male mice","authors":"Shelby K. Reid ,&nbsp;Miranda E. Leal-Garcia ,&nbsp;Ashley V. Tran ,&nbsp;Nicole T. Rehtmeyer ,&nbsp;Isha S. Shirvaikar ,&nbsp;Megan A. Kirchhoff ,&nbsp;Alyson O. Narvaez ,&nbsp;Dylan A. McCreedy","doi":"10.1016/j.bbi.2025.04.033","DOIUrl":"10.1016/j.bbi.2025.04.033","url":null,"abstract":"<div><div>After traumatic spinal cord injury (SCI), inflammation and other reactive processes exacerbate tissue damage and impair long-term motor recovery. Extracellular traps (ETs) are an immune cell effector function first described in neutrophils wherein chromatin is decondensed, decorated with cytotoxic granule enzymes, and expelled from the cell body. Recently, ETs have been linked to poor functional outcomes in SCI; however, translatable agents to prevent ET-mediated damage after SCI have yet to be explored. We assessed recombinant human (rh) DNase (trade name Pulmozyme) as a potential therapeutic that could be repurposed to break down ETs after SCI. To determine the timing of treatment, we characterized the timeline of ET formation in a thoracic contusion model of SCI in mice. We found that ETs levels increased in the injured spinal cord by 4 h post injury (hpi), peaking within 24 hpi. When rhDNase was administered at 1 hpi, DNase activity in the serum remained elevated for 24 hpi with a corresponding increase in circulating ET fragments. At 6 hpi, blood-spinal cord barrier permeability was attenuated in rhDNase-treated animals. Long-term functional hind limb recovery, as assessed by the ladder rung walking test, was improved at 35 dpi in rhDNase-treated animals compared to vehicle-treated controls. RhDNase-treated animals also exhibited shorter SCI lesion lengths at 35 dpi. Altogether, our data demonstrate the potential of rhDNase as an anti-ET therapeutic to improve long-term SCI outcomes.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 456-468"},"PeriodicalIF":8.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143873872","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":"A pre-existing chronic Toxoplasma gondii infection promotes epileptogenesis and neuropathology in a mouse model of mesial temporal lobe epilepsy","authors":"Tamara L. Baker ,&nbsp;David K. Wright ,&nbsp;Peravina Thergarajan ,&nbsp;Alessandro D. Uboldi ,&nbsp;Anh Vo ,&nbsp;Trevor Wilson ,&nbsp;Christopher J. Tonkin ,&nbsp;Terence J. O’Brien ,&nbsp;Ana Antonic-Baker ,&nbsp;Michael J. Asmussen ,&nbsp;Stuart J. McDonald ,&nbsp;Pablo M. Casillas-Espinosa ,&nbsp;Nigel C. Jones ,&nbsp;Idrish Ali ,&nbsp;Mujun Sun ,&nbsp;Sandy R. Shultz","doi":"10.1016/j.bbi.2025.04.026","DOIUrl":"10.1016/j.bbi.2025.04.026","url":null,"abstract":"<div><h3>Objective</h3><div>There is initial evidence that the common neurotropic parasite <em>Toxoplasma gondii</em> is a risk factor for the development of epilepsy; however, whether it influences epileptogenesis is unknown. This study investigated whether a pre-existing chronic <em>T. gondii</em> infection alters epileptogenesis and neuropathology in a mouse model of mesial temporal lobe epilepsy.</div></div><div><h3>Methods</h3><div>Male and female C57BL/6Jax mice were intraperitoneally administered <em>T. gondii</em> tachyzoites or vehicle control. After 6 weeks, mice underwent self-sustained electrical status epilepticus (SSSE) through an implanted bipolar electrode, or a sham procedure. Continuous video-EEG recordings were taken 0–4- and 12–16-weeks post-SSSE to detect spontaneous seizures. Neuroinflammatory markers were assessed within 1-week post-SSSE, behavior testing was done at 8–12 weeks post-SSSE, and <em>ex vivo</em> MRI was conducted at 16 weeks post-SSSE.</div></div><div><h3>Results</h3><div>Male <em>T. gondii</em> + SSSE mice had an increased incidence of epilepsy compared to Vehicle + SSSE, while female <em>T. gondii</em> + SSSE mice had worse seizure severity compared to non-infected SSSE mice. There was amplified neuroinflammation in both male and female <em>T. gondii</em> + SSSE mice compared to Vehicle + SSSE mice. <em>T. gondii</em> infection in the absence of SSSE also resulted in epilepsy and neuroinflammation. MRI revealed abnormalities in brain morphology in <em>T. gondii</em> + SSSE male and female mice and changes in white matter integrity in male <em>T. gondii</em> + SSSE mice, compared to both non-infected SSSE and <em>T. gondii</em> control mice. SSSE and <em>T. gondii</em> infection impacted anxiety and spatial memory in males, and anxiety and social behavior in females.</div></div><div><h3>Interpretation</h3><div>These findings demonstrate that a chronic <em>T. gondii</em> infection can result in epilepsy, and that a pre-existing <em>T. gondii</em> infection exacerbates epileptogenesis following a brain insult, in mice.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 440-455"},"PeriodicalIF":8.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143874413","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":"Investigating the relationship between toll-like receptor activity, low-grade inflammation and cognitive deficits in schizophrenia patients – A mediation analysis","authors":"Saahithh Redddi Patlola ,&nbsp;Laurena Holleran ,&nbsp;Maria R. Dauvermann ,&nbsp;Karolina Rokita ,&nbsp;Aodán Laighneach ,&nbsp;Brian Hallahan ,&nbsp;Ross McManus ,&nbsp;Marcus Kenyon ,&nbsp;Colm McDonald ,&nbsp;Derek W. Morris ,&nbsp;John P. Kelly ,&nbsp;Gary Donohoe ,&nbsp;Declan P. McKernan","doi":"10.1016/j.bbi.2025.04.024","DOIUrl":"10.1016/j.bbi.2025.04.024","url":null,"abstract":"<div><h3>Background</h3><div>Schizophrenia is a debilitating psychiatric illness. Many studies report alterations in immune biomarkers (cytokines) in such patients. In addition, such prolonged low-grade inflammatory responses are associated with lowered cognitive performance. In this study, we investigated whether the expression and activity of Toll-like receptors (TLRs), receptors involved in initiating innate immune responses, are associated with the reported immune changes and, if so, whether they are associated with cognitive deficits in such patients.</div></div><div><h3>Methods</h3><div>300 participants (202 healthy controls (HC) and 98 patients with schizophrenia (SZ)) were recruited. A battery of cognitive tasks using WAIS-III and CANTAB were administered to the participants. Whole blood collected from participants was used to assess TLR2, 3, and 4 activity. mRNA expression of cytokines and TLR1-10 were quantified using RT-QPCR. Using ELISA, plasma was analysed for basal levels of cytokines such as IL-6, IL-8, IL-10, IL-12, TNF-α, IFN-γ and C-reactive proteins (CRP).</div></div><div><h3>Results</h3><div>We found significantly elevated plasma levels of IL-6, IL-8, IL-10, TNF-α, and CRP in the SZ group. In the SZ patient-only group, significantly higher levels of TLR2 and −4 activity (as measured by IL-6, IL-8, and IL-10 release following agonist stimulation) were observed. Significant negative associations in patients were observed between plasma IL-6 levels and measures of attention &amp; processing speed and working memory; IL-8 and intelligence quotient; TNF-α and logical memory; and social cognition and IL-10 and CRP. Multiple-linear regression analysis suggests that TLR2 and TLR4 activity was associated with increased and decreased cytokine levels respectively and decreased cognitive performance. Finally, the significant association between TLR activity and decreased cognitive performance was mediated by IL-6 and IL-8.</div></div><div><h3>Conclusion</h3><div>We have demonstrated that patients with schizophrenia have elevated protein and mRNA expression of a range of cytokines and Toll-like receptors. Some of these changes are associated with deficits in cognition. Finally, our study has demonstrated a modest relationship between TLR activity and cognitive deficits in schizophrenia patients in a manner that may be mediated by IL-6 and IL-8.</div></div>","PeriodicalId":9199,"journal":{"name":"Brain, Behavior, and Immunity","volume":"128 ","pages":"Pages 529-539"},"PeriodicalIF":8.8,"publicationDate":"2025-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143886468","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}