Brain, behavior, & immunity - health最新文献

{"title":"Neuroimmune axis: Linking environmental factors to pancreatic β-cell dysfunction in Diabetes","authors":"Luz Andreone","doi":"10.1016/j.bbih.2024.100926","DOIUrl":"10.1016/j.bbih.2024.100926","url":null,"abstract":"<div><div>Pancreatic β-cells are specialized in secreting insulin in response to circulating nutrients, mainly glucose.</div><div>Diabetes is one of the most prevalent endocrine-metabolic diseases characterized by an imbalance in glucose homeostasis, which result mainly from lack of insulin production (type 1 diabetes) or insufficient insulin and peripheral insulin resistance (type 2 diabetes), both influenced by genetic and environmental components. Pancreatic β-cell dysfunction and islet inflammation are common characteristics of both types of the disease. Pancreatic islets are a highly innervated tissue whose function can be influenced by the brain, either directly through the autonomic nervous system or indirectly via neuroendocrine mechanisms. In addition, it is well-established that there is a fine-tuned communication between the immune and neuroendocrine tissues in maintaining endocrine pancreas homeostasis.</div><div>Various psycho-social, physico-chemical and lifestyle environmental factors have been associated with diabetes risk. In this review, I briefly comment on certain aspects of the psycho-neuro-immune interactions that link environmental factors and the endocrine pancreas, leading to metabolic health or diabetes<strong>.</strong></div><div>Interdisciplinary research, embracing new and broader perspectives, should be conducted to explore strategies for preventing or slowing down the constant increase in diabetes worldwide.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100926"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142985667","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chemokine associations with blood cerebrospinal fluid (CSF) barrier permeability and delirium","authors":"Paul Denver ,&nbsp;Lucas Tortorelli ,&nbsp;Karen Hov ,&nbsp;Jens Petter Berg ,&nbsp;Lasse M. Giil ,&nbsp;Arshed Nazmi ,&nbsp;Ana Lopez-Rodriguez ,&nbsp;Daire Healy ,&nbsp;Carol Murray ,&nbsp;Robyn Barry ,&nbsp;Leiv Otto Watne ,&nbsp;Colm Cunningham","doi":"10.1016/j.bbih.2024.100920","DOIUrl":"10.1016/j.bbih.2024.100920","url":null,"abstract":"<div><div>Delirium is a highly prevalent neuropsychiatric syndrome characterised by acute and fluctuating impairments in attention and cognition. Mechanisms driving delirium are poorly understood but it has been suggested that blood cytokines and chemokines cross the blood brain barrier during delirium, directly impairing brain function. It is not known whether these molecules reach higher brain levels when the blood cerebrospinal fluid barrier (BCSFB) is impaired. Here, in human hip-fracture patients, we tested the influence of BCSFB integrity on CSF levels of chemokines and assessed their association with delirium. CSF levels of IP-10, eotaxin, eotaxin 3 and TARC showed weak to moderate correlations with BCSFB permeability, as measured by the Q_albumin ratio, while MCP1, IL-8, MIP1α and MIP1β showed no significant correlation. Chemokines were not associated with delirium in univariate analysis or when stratified on dementia status, but exploratory analyses showed that elevated Eotaxin (CCL11) and MIP1α (CCL3) were associated with prevalent delirium. Modelling acute systemic inflammation, we used bacterial LPS (250 μg/kg) or sterile laparotomy surgery in mice to demonstrate <em>de novo</em> synthesis of chemokines at the choroid plexus (CP) and microvasculature. Gene expression data showed CP-enriched expression of <em>Il1b, Tnfa, Cxcl1</em> and <em>Ccl3</em> in both models and immunohistochemistry showed cytokine and chemokine synthesis in CP stromal (IL-1β, CCL2/MCP1) or epithelial cells (CXCL10/IP-10) cells and at the microvasculature. Larger studies are required to confirm these human findings on chemokine associations with BCSFB permeability and prevalent delirium. Preclinical studies are warranted to determine whether chemokines might play a role in the pathophysiology of delirium.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100920"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11750293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143017333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deep immunophenotyping of circulating immune cells in major depressive disorder patients reveals immune correlates of clinical course and treatment response","authors":"Fabiola Stolfi ,&nbsp;Claudio Brasso ,&nbsp;Davide Raineri ,&nbsp;Virginia Landra ,&nbsp;Camilla Barbero Mazzucca ,&nbsp;Ali Ghazanfar ,&nbsp;Lorenza Scotti ,&nbsp;Riccardo Sinella ,&nbsp;Vincenzo Villari ,&nbsp;Giuseppe Cappellano ,&nbsp;Paola Rocca ,&nbsp;Annalisa Chiocchetti","doi":"10.1016/j.bbih.2024.100942","DOIUrl":"10.1016/j.bbih.2024.100942","url":null,"abstract":"<div><div>Major Depressive Disorder (MDD) is a widespread psychiatric condition impacting social and occupational functioning, making it a leading cause of disability. The diagnosis of MDD remains clinical, based on the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 criteria, as biomarkers have not yet been validated for diagnostic purposes or as predictors of treatment response. Traditional treatment strategies often follow a one-size-fits-all approach obtaining suboptimal outcomes for many patients who fail to experience response or recovery. Several studies have reported an association between MDD and immune system dysregulation, but few have focused on the deep characterization of circulating cells, during the acute phase of MDD. This work aimed at immunophenotyping peripheral blood cells in the relapse phase of the disorder, to identify relevant cell populations for clinical monitoring of patients. Multiparametric analysis was performed on the peripheral blood of 60 MDD patients using flow cytometry to identify lymphocytes (naïve/effector, memory, regulatory) and myeloid cells (dendritic cells, monocytes). We studied the associations between immunophenotype and depressive symptoms, social and working functioning, and subjective quality of life during the acute phase and after three months of treatment. Multivariate analysis showed that CD4⁺ terminally differentiated effector memory (TEMRA) were associated with more depressive symptoms with a particular emphasis on anhedonic features and worse social and working functioning and quality of life. CD8⁺ TEMRA were associated with those depressive symptoms related to hopelessness. Conversely, ICOS + Tregs were associated with low-intensity suicidal ideation, suggestive of a protective role. Baseline T CD4⁺ effector memory (EM) was a negative predictor of reduction of depressive symptoms after three months of treatment, whilst plasmacytoid dendritic cells (pDC) were predicting reduction of hopelessness. These results confirm the involvement of the immune system in MDD and demonstrate the existence of immunological signatures associated with the severity of major depressive episodes and treatment response that could guide clinical monitoring and future personalized therapies.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100942"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061072","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of a multiplex immune marker panel with incident cognitive impairment and dementia: The Northern Manhattan Study","authors":"Mohammad Abdurrehman Sheikh ,&nbsp;Michelle P. Moon ,&nbsp;Clinton B. Wright ,&nbsp;Jose Gutierrez ,&nbsp;Minghua Liu ,&nbsp;Tatjana Rundek ,&nbsp;Ken Cheung ,&nbsp;Mady Hornig ,&nbsp;Mitchell S.V. Elkind","doi":"10.1016/j.bbih.2024.100937","DOIUrl":"10.1016/j.bbih.2024.100937","url":null,"abstract":"<div><h3>Objective</h3><div>To determine whether a panel of immune markers adds significant information to known correlates of risk of dementia and cognitive impairment.</div></div><div><h3>Background</h3><div>The impact of immune mechanisms on dementia risk is incompletely characterized.</div></div><div><h3>Design/methods</h3><div>A subsample of the Northern Manhattan Study, a prospective cohort study in the racially/ethnically diverse population of New York City, underwent comprehensive neuropsychological testing up to three times, at approximately 5-year intervals. Cognitive outcomes were adjudicated as no cognitive impairment, mild cognitive impairment (MCI), or dementia. Immune markers were assessed using a multiplex immunoassay on plasma samples collected at the time of the first neuropsychological test. Least absolute shrinkage and selection operator (LASSO) techniques were employed to yield a panel of immune markers linearly related to the outcome of dementia/MCI vs. no cognitive impairment. Nested logistic regression models were run to determine the independent association of the immune marker panel with dementia/MCI after adjusting for other predictors of risk.</div></div><div><h3>Results</h3><div>Among 1179 participants (mean age 70.0 ± 8.9 years, 60% women, 68% Hispanic), immune markers improved model fit above demographic and vascular risk factors (p-value for likelihood ratio test &lt;0.0001) as correlates of MCI/dementia. Individual immune markers found to be associated with dementia/MCI were C-X-C Motif Chemokine Ligand 9 (CXCL9) and C-C Motif Chemokine Ligand 2 (CCL2). The effect of the immune markers was comparable to traditional risk factors, with CCL2 (per SD) having almost the same effect as 1 year of aging and CXCL9 (per SD) showing approximately twice this magnitude.</div></div><div><h3>Conclusion</h3><div>Immune markers are associated with cognitive decline and dementia outcomes in a multi-ethnic cohort. More work is needed to further characterize these associations and determine therapeutic strategies. (Funded by the National Institute of Health/National Institute of Neurological Disorders and Stroke; grant number R01 29993 (Sacco/Elkind)).</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100937"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11757223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Repeated social defeat in male mice induced unique RNA profiles in projection neurons from the amygdala to the hippocampus","authors":"Rebecca G. Biltz ,&nbsp;Wenyuan Yin ,&nbsp;Ethan J. Goodman ,&nbsp;Lynde M. Wangler ,&nbsp;Amara C. Davis ,&nbsp;Braedan T. Oliver ,&nbsp;Jonathan P. Godbout ,&nbsp;John F. Sheridan","doi":"10.1016/j.bbih.2024.100908","DOIUrl":"10.1016/j.bbih.2024.100908","url":null,"abstract":"<div><div>Chronic stress increases the incidence of psychiatric disorders including anxiety, depression, and posttraumatic stress disorder. Repeated Social Defeat (RSD) in mice recapitulates several key physiological, immune, and behavioral changes evident after chronic stress in humans. For instance, neurons in the prefrontal cortex, amygdala, and hippocampus are involved in the interpretation of and response to fear and threatful stimuli after RSD. Therefore, the purpose of this study was to determine how stress influenced the RNA profile of hippocampal neurons and neurons that project into the hippocampus from threat appraisal centers. Here, RSD increased anxiety-like behavior in the elevated plus maze and reduced hippocampal-dependent novel object location memory in male mice. Next, pan-neuronal (Baf53 b-Cre) RiboTag mice were generated to capture ribosomal bound mRNA (i.e., active translation) activated by RSD in the hippocampus. RNAseq revealed that there were 1694 differentially expressed genes (DEGs) in hippocampal neurons after RSD. These DEGs were associated with an increase in oxidative stress, synaptic long-term potentiation, and neuroinflammatory signaling. To further examine region-specific neural circuitry associated with fear and anxiety, a retrograde-adeno-associated-virus (AAV2rg) expressing Cre-recombinase was injected into the hippocampus of male RiboTag mice. This induced expression of a hemagglutinin epitope in neurons that project into the hippocampus. These AAV2rg-RiboTag mice were subjected to RSD and ribosomal-bound mRNA was collected from the amygdala for RNA-sequencing. RSD induced 677 DEGs from amygdala projections. Amygdala neurons that project into the hippocampus had RNA profiles associated with increased synaptogenesis, interleukin-1 signaling, nitric oxide, and reactive oxygen species production. Using a similar approach, there were 1132 DEGs in neurons that project from the prefrontal cortex. These prefrontal cortex neurons had RNA profiles associated with increased synaptogenesis, integrin signaling, and dopamine feedback signaling after RSD. Collectively, there were unique RNA profiles of stress-influenced projection neurons and these profiles were associated with hippocampal-dependent behavioral and cognitive deficits.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100908"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11667635/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142886550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid mediators in post-mortem brain samples from patients with Alzheimer's disease: A systematic review","authors":"Aidan D. Tyrrell ,&nbsp;Giulia Cisbani ,&nbsp;Mackenzie E. Smith ,&nbsp;Chuck T. Chen ,&nbsp;Yue-Tong Chen ,&nbsp;Raphael Chouinard-Watkins ,&nbsp;Kathryn E. Hopperton ,&nbsp;Ameer Y. Taha ,&nbsp;Richard P. Bazinet","doi":"10.1016/j.bbih.2024.100938","DOIUrl":"10.1016/j.bbih.2024.100938","url":null,"abstract":"<div><div>A proposed contributor to Alzheimer's disease (AD) pathology is the induction of neuroinflammation due to tau and beta-amyloid protein accumulation causing neuronal injury and dysfunction. Dysregulation of lipid mediators derived from polyunsaturated fatty acids may contribute to this inflammatory response in the brain of patients with AD, yet the literature has not yet been systematically reviewed. A systematic search was conducted in Medline, Embase and PsychINFO for articles published up to April 22, 2024. Papers were included if they measured levels of lipid mediators and/or enzymes involved in their production in <em>post-mortem</em> brain samples from patients with AD and control without neurological disease. A total of 50 relevant studies were identified. Despite heterogeneity in the results, pro-inflammatory lipid mediators, including 5-, 11-, 12- and 15-hydroxyeicosatetraenoic acid oxylipins and prostaglandin D2, were significantly higher, while anti-inflammatory lipoxin A4 and DHA-derived docosanoids were significantly lower in brains of patients with AD compared to control (16 studies). Thirty-seven articles reported on enzymes, with 32 reporting values for enzyme level changes between AD and controls. Among the 32 articles, the majority reported on levels of cyclooxygenase (COX) (18/32), with fewer studies reporting on phospholipase (8/32), lipoxygenase (LOX) (4/32) and prostaglandin E synthase (4/32). Enzyme levels also exhibited variability in the literature, with a trend towards elevated expression of enzymes involved in the pro-inflammatory response, including COX and LOX enzymes. Overall, these results are consistent with the involvement of neuroinflammation in the pathogenesis of AD measured by lipid mediators. However, the specific contribution of each lipid metabolite and enzymes to either the progression or persistence of AD remains unclear, and more research is required.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100938"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11782888/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fatigue in intensive care unit survivors with COVID-19: An observational cohort study","authors":"Kristina Struksnes Fjone ,&nbsp;Milada Hagen ,&nbsp;Jon Henrik Laake ,&nbsp;Luis Romundstad ,&nbsp;Eirik Alnes Buanes ,&nbsp;Kristin Hofsø","doi":"10.1016/j.bbih.2025.100943","DOIUrl":"10.1016/j.bbih.2025.100943","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100943"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11773270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143061074","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction between Th17 and central nervous system in multiple sclerosis","authors":"Shixin Lai,&nbsp;Xiaomin Wu,&nbsp;Yue Liu,&nbsp;Bo Liu,&nbsp;Haiqi Wu,&nbsp;Kongyang Ma","doi":"10.1016/j.bbih.2024.100928","DOIUrl":"10.1016/j.bbih.2024.100928","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100928"},"PeriodicalIF":3.7,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143026075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of machine learning models for the prediction of Alzheimer's: In search of the best performance","authors":"Michael Cabanillas-Carbonell ,&nbsp;Joselyn Zapata-Paulini","doi":"10.1016/j.bbih.2025.100957","DOIUrl":"10.1016/j.bbih.2025.100957","url":null,"abstract":"<div><div>Alzheimer's is a progressive and degenerative disease affecting millions worldwide, incapacitating them physically and cognitively. This study aims to perform a comparative analysis of Machine Learning models to determine the model with the best performance in predicting Alzheimer's disease. The models used were Random Forest (RF), Adaptive Boosting (AdaBoost), Support Vector Machine (SVM), K-nearest Neighbors (KNN), and Logistic Regression (LR). Two datasets called OASIS were used to train the models, the first one had a total of 436 records and 12 variables, while the second one stored 373 records and 15 variables. The article's content is divided into six main sections: introduction, literature review, methodological approach, results, discussions, and conclusions. After processing and pooling the datasets, RF, SVM, and LR proved the best predictors, achieving 96% accuracy, precision, sensitivity, and F1 score. This study highlights the efficacy of RF, SVM, and LR in predicting Alzheimer's disease, offering a significant advance toward understanding and management of this disease, which supports the relevance of implementing these models in future research and clinical applications.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100957"},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143350708","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation in blood-brain barrier integrity and susceptibility to immune cell penetration in a mouse model of Dravet syndrome","authors":"Cristina Alonso ,&nbsp;Alicia García-Culebras ,&nbsp;Valentina Satta ,&nbsp;Inés Hernández-Fisac ,&nbsp;Álvaro Sierra ,&nbsp;José A. Guimaré ,&nbsp;Ignacio Lizasoain ,&nbsp;Javier Fernández-Ruiz ,&nbsp;Onintza Sagredo","doi":"10.1016/j.bbih.2025.100955","DOIUrl":"10.1016/j.bbih.2025.100955","url":null,"abstract":"<div><div>Dravet Syndrome (DS) is a pediatric encephalopathy caused by mutations in <em>Scn1a</em> gene encoding the α1 subunit of the Na_V1.1 voltage-gated sodium channel, which lead to early febrile seizures that progress to severe tonic-clonic seizures and several long-term behavioural comorbidities. In the present study, we have investigated whether a possible early deterioration in the blood-brain barrier (BBB) may facilitate the infiltration of immune cells to the brain parenchyma, which may contribute to these pathogenic events. In this study, conditional knock-in <em>Scn1a</em>-A1783V mice and their controls were used at the postnatal day (PND25): (i) to compare their levels of several immune cell populations in the bone marrow and blood; and (ii) to analyze several BBB proteins, as well as the occurrence of immune cell infiltration and endogenous immunoglobulin G (IgG) extravasation into the brain parenchyma. Our data revealed an elevation in the number of neutrophils in the blood of DS mice, but not of B- and T-cells, despite the levels of these immune cells were significantly reduced in the bone marrow. The elevated number of blood neutrophils did not apparently originate their infiltration into the hippocampus of DS mice as an immunofluorescence analysis indicated, and the same happened in B- and T-cells. However, the levels of endogenous IgG in this brain structure were significantly elevated in DS mice compared to controls, directly indicating the occurrence of extravasation into the brain parenchyma and indirectly that the BBB in DS mice may be relatively affected, a fact confirmed by the reduction in the levels of BBB-related proteins such as ZO-1 in these mice. In conclusion, our results support the occurrence of certain degree of deterioration in the BBB in DS, which may facilitate the infiltration of immune cells to the brain, then contributing to the pathogenesis in this disease.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100955"},"PeriodicalIF":3.7,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143377216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}