Brain, behavior, & immunity - health最新文献

{"title":"Neuroimmunology of psoriasis: Possible roles for calcitonin gene-related peptide in its pathogenesis","authors":"Joshua Kotlyar ,&nbsp;Richard D. Granstein","doi":"10.1016/j.bbih.2025.100958","DOIUrl":"10.1016/j.bbih.2025.100958","url":null,"abstract":"<div><div>The nervous system has a complex interplay with the immune system, especially at barrier sites such as the skin. This allows it to play a role in a variety of cutaneous inflammatory disorders such as psoriasis, exerting effects on various immune cells via effector molecules such as neuropeptides. In this review, we discuss the role of calcitonin gene-related peptide in modulating the immune system and inflammation, with a focus on psoriasis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100958"},"PeriodicalIF":3.7,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143324896","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":"The relationship between cognitive function and neuropsychiatric disorders with quantitative electroencephalogram (qEEG) on long COVID syndrome patients","authors":"Yetty Ramli ,&nbsp;Pukovisa Prawiroharjo ,&nbsp;Winnugroho Wiratman ,&nbsp;Eric Tenda ,&nbsp;Nurhadi Ibrahim ,&nbsp;Damar Susilaradeya ,&nbsp;Abdi Reza ,&nbsp;Jennifer Agatha ,&nbsp;Rejoel Siagian ,&nbsp;Hazrina Fauhan ,&nbsp;Florencia Evelyn ,&nbsp;Yoshikazu Ugawa ,&nbsp;Prasandhya Yusuf","doi":"10.1016/j.bbih.2025.100954","DOIUrl":"10.1016/j.bbih.2025.100954","url":null,"abstract":"<div><h3>Background</h3><div>The COVID-19 pandemic has resulted in long-term consequences for a subset of affected individuals, known as long COVID syndrome. The neurological and psychiatric effects of this condition remain incompletely understood. This study aims to evaluate heightened common mental disorders in long COVID through assessing psychiatric, cognitive, neurophysiological aspects, and emphasizing lasting mental health impacts.</div></div><div><h3>Methods</h3><div>This cross-sectional study compared patients with long COVID to those who had recovered from COVID-19 without residual symptoms using quantitative electroencephalogram (qEEG) analysis. We conducted qEEG analyses, and Montreal Cognitive Assessment (MoCA) and Self-Rating Questionnaire (SRQ) tests on participants. Analyses included brain spectrum examination, hemispheric asymmetry, and inter-electrode connectivity.</div></div><div><h3>Results</h3><div>Analyses revealed lower MoCA scores in the memory domain were lower in the long COVID group (Mann Whitney <em>U</em>test), indicating that individuals with long COVID experience more substantial cognitive deficits. There is no statistical difference for spectrum examination and hemispheric asymmetry observed in the qEEG data between the COVID and long COVID groups. Connectivity analysis showed statistically significant higher connectivity in temporal-occipital (T6-O2) in long COVID groups (Mann Whitney <em>U</em>test).</div></div><div><h3>Conclusion</h3><div>Our findings underscore the persistent neuropsychiatric impact of COVID-19, particularly in long COVID patients. Notably, working memory deficits in MoCA scores were identified as one of the most frequent neuropsychological symptoms in these individuals. Decreased brain connectivity indicates cognitive-sensorimotor decline and is confirmed by the frequent brain fog symptoms in long COVID.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100954"},"PeriodicalIF":3.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143571","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":"Understanding the potential impact of trimester-specific maternal immune activation due to SARS-CoV-2 on early human neurodevelopment and the role of cytokine balance","authors":"Alexandre Díaz-Pons ,&nbsp;Sergio Castaño-Castaño ,&nbsp;Víctor Ortiz-García de la Foz ,&nbsp;Ángel Yorca-Ruiz ,&nbsp;Carlos Martínez-Asensi ,&nbsp;Eva Munarriz-Cuezva ,&nbsp;Rosa Ayesa-Arriola","doi":"10.1016/j.bbih.2025.100956","DOIUrl":"10.1016/j.bbih.2025.100956","url":null,"abstract":"<div><h3>Purpose</h3><div>The COVID-19 pandemic presents significant future health challenges. Its impact on pregnant women and their newborn is a particular area of concern. This study aims to examine the potential role of maternal immune activation (MIA), due to SARS-CoV-2 infection, on early neurodevelopment.</div></div><div><h3>Methods</h3><div>We analysed 107 mother-infant dyads from the COGESTCOV-19 study in Cantabria, Spain, which included 59 SARS-CoV-2 exposed (cases) and 48 unexposed (controls) mothers, recruited between December 2020 and February 2022. Cytokine levels (IL-6 and IL-10) were obtained from maternal blood and cord blood. Neurodevelopment was assessed using the Neonatal Behavioral Assessment Scale (NBAS) at six weeks of age. Trimester of infection was considered in the main analyses.</div></div><div><h3>Results</h3><div>Results showed no significant overall delays in early neurodevelopment due to maternal SARS-CoV-2 infection. Control infants performed better in some NBAS items. However, cases infants showed trimester-specific differences. First-trimester exposure was related to motor and reflex delays, second-trimester to poorer performances in motor tasks and autonomic stability, and third-trimester to weaker state organization, regulation, and reflexes. Some correlations between cytokine levels and NBAS performance showed moderate associations.</div></div><div><h3>Conclusions</h3><div>These findings highlight the need for ongoing neurodevelopmental monitoring of infants born during the COVID-19 pandemic. The study enhances our understanding of MIA's impact on early development, emphasizing the importance of addressing homeostatic mechanisms in mothers and newborns.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100956"},"PeriodicalIF":3.7,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143143570","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":"Evaluating sleep's role in type 2 diabetes mellitus: Evidence from NHANES","authors":"Jijun Zhang ,&nbsp;Chuanli Yang ,&nbsp;Jie An ,&nbsp;Yunhe Fan ,&nbsp;Xiushan Dong","doi":"10.1016/j.bbih.2025.100953","DOIUrl":"10.1016/j.bbih.2025.100953","url":null,"abstract":"<div><h3>Background</h3><div>Evidence is limited regarding the relationship between sleep factors (self-reported sleep disorder diagnosis, subjective sleep difficulties, and sleep duration), sleep patterns, and risk of type 2 diabetes mellitus (T2D). Thus, this study aims to investigate the relationship between sleep factors, sleep patterns, and the risk of T2D using data from the National Health and Nutrition Examination Survey (NHANES).</div></div><div><h3>Methods</h3><div>A total of 14,652 individuals aged ≥18 years from the NHANES (2005–2014) were enrolled with complete data on sleep factors, T2D, and covariates. Information on self-reported sleep disorder diagnosis, subjective sleep difficulties, and sleep duration was collected during in-home visits by trained interviewers using the Computer-Assisted Personal Interviewing system. The sleep pattern was derived from scoring three mentioned factors: no self-reported sleep disorder diagnosis, no subjective sleep difficulties, and sleep duration of 7–9 h were classified as low-risk (score 0), while the presence of self-reported sleep disorder diagnosis, subjective sleep difficulties, or sleep duration &lt;7 or &gt;9 h were classified as high-risk (score 1). Cumulative scores range from 0 to 3, with 0 indicating a healthy sleep pattern, 1 an intermediate sleep pattern, and 2–3 a poor sleep pattern, respectively. Weighted logistic regression was conducted to assess the association of sleep factors and sleep patterns with the risk of T2D.</div></div><div><h3>Results</h3><div>Self-reported sleep disorder diagnosis (odds ratio (OR) = 1.32, <em>P</em> = 0.01), subjective sleep difficulties (OR = 1.29, <em>P</em> = 0.001), and sleep deprivation (&lt;7 h; OR = 1.20, <em>P</em> = 0.01) were significantly positive with T2D. Poor sleep pattern also significantly increased T2D risk (OR = 1.52, <em>P</em> &lt; 0.0001). Moreover, subgroup analyses stratified by age and BMI (body mass index) further confirmed that the positive association between sleep patterns and T2D was consistent and robust across groups.</div></div><div><h3>Conclusion</h3><div>Our findings indicate that poorer sleep patterns are associated with an increased risk of T2D. These results emphasize the importance of sleep management in T2D prevention. Further prospective studies are needed to investigate the causal or bidirectional relationship between sleep and T2D risk, as well as the underlying molecular mechanisms.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100953"},"PeriodicalIF":3.7,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144334","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":"Glial activation among individuals with neurological post-acute sequelae of coronavirus disease 2019: A positron emission tomography study of brain fog using [18F]-FEPPA","authors":"Sean A.P. Clouston ,&nbsp;Paul Vaska ,&nbsp;Tesleem Babalola ,&nbsp;John Gardus III ,&nbsp;Chuan Huang ,&nbsp;Nicola Soriolo ,&nbsp;Ashley Fontana ,&nbsp;Christine DeLorenzo ,&nbsp;Ramin Parsey ,&nbsp;Benjamin J. Luft","doi":"10.1016/j.bbih.2025.100945","DOIUrl":"10.1016/j.bbih.2025.100945","url":null,"abstract":"<div><h3>Background</h3><div>This study examined the regional distribution of glial activation in essential workers with neurological post-acute sequelae of coronavirus disease 2019 (COVID-19) infections (N-PASC).</div></div><div><h3>Methods</h3><div>We injected ≤185 MBq of [¹⁸F]-FEPPA as an intravenous bolus and positron-emission tomography over 2 h. To measure distribution volume (V_T) we recruited 24 essential workers (14 N-PASC, 10 Never-COVID-19 Controls, of whom 22 successfully placed arterial lines). Individuals with low binding affinity were excluded from this study, and V_T was adjusted for translocator protein genotype. Analyses that passed the false discovery rate are reported.</div></div><div><h3>Results</h3><div>Participants at midlife survived mild to moderate COVID-19 without hospitalization but reported onset of post-acute sequelae of COVID-19 (PASC) for, on average, 22 months before undergoing neuroimaging. Hippocampal V_T was higher (V_T = 1.70, 95% C.I. = [1.30–2.21], p = 0.001) in participants with persistent brain fog after COVID-19, reflecting an increase of 10.58 mL/cm³ in V_T (area under the receiver-operating curve, AUC = 0.95 [0.85–1.00]). At a cutoff of 10.6, sensitivity/specificity/accuracy were 0.88/0.93/0.91.</div></div><div><h3>Conclusion</h3><div>The results from this study imply that neuroimmune response is a distinct and identifiable characteristic of brain fog after COVID-19. Results suggest that [¹⁸F]-FEPPA could be used to support N-PASC diagnosis.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100945"},"PeriodicalIF":3.7,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11786203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143082195","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":"Gut microbiota metabolites, secretory immunoglobulin A and Bayley-III cognitive scores in children from the CHILD Cohort Study","authors":"Aline Davias ,&nbsp;Myah Verghese ,&nbsp;Sarah L. Bridgman ,&nbsp;Hein M. Tun ,&nbsp;Catherine J. Field ,&nbsp;Matthew Hicks ,&nbsp;Jacqueline Pei ,&nbsp;Anne Hicks ,&nbsp;Theo J. Moraes ,&nbsp;Elinor Simons ,&nbsp;Stuart E. Turvey ,&nbsp;Padmaja Subbarao ,&nbsp;James A. Scott ,&nbsp;Piushkumar J. Mandhane ,&nbsp;Anita L. Kozyrskyj","doi":"10.1016/j.bbih.2025.100946","DOIUrl":"10.1016/j.bbih.2025.100946","url":null,"abstract":"<div><h3>Background</h3><div>Dysbiosis of the gut microbiota has been demonstrated in neurodevelopmental disorders but the underlying mechanisms that may explain these associations are poorly understood. Gut secretory immunoglobulin A (SIgA) binds pathogenic microbes, preventing mucosal penetration. Gut microbes also influence SIgA production and its binding characteristics through short-chain fatty acid (SCFA) metabolites, allowing them to regulate the immune response. Serum IgA deficiency has been noted in children with autism spectrum disorders (ASD). In this study, we aimed to determine whether SIgA level in infancy is associated with gut microbiota taxonomy and metabolites, and neurodevelopmental outcomes in preschool children.</div></div><div><h3>Methods</h3><div>For a subsample of 178 children from the Canadian CHILD Cohort Study, gut microbiota of fecal samples collected at 3–4 months and 12 months was profiled using 16S rRNA sequencing. Gut bacterial metabolites levels and SIgA level were measured by nuclear magnetic resonance (NMR) based metabolomics and SIgA enzyme-linked immunosorbent assay at 3–4 months, respectively. Bayley-III Scale of Infant Development was assessed at 12 and 24 months. We evaluated direct relationships in multiple linear regression models and putative causal relationships in statistical mediation models.</div></div><div><h3>Results</h3><div>Propionate and butyrate levels at 3–4 months were associated with decreased Bayley cognitive score at 24 months (p-values: 0.01 and 0.02, respectively) in adjusted multiple linear regression models, but when we investigated an indirect relationship mediated by decreased SIgA level at 3–4 months, it did not reach statistical significance (p-values: 0.18 and 0.20, respectively). Lactate level at 3–4 months was associated with increased Bayley cognitive score at 24 months in adjusted multiple linear regression models (p-value: 0.01), but the statistical model mediated by increased SIgA level at 3–4 months did not reach statistical significance neither (p-value: 0.20).</div></div><div><h3>Conclusions</h3><div>Our study contributes to growing evidence that neurodevelopment is influenced by the infant gut microbiota and that it might involve SIgA level, but larger studies are required.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100946"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144336","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":"Immune links in comorbid depression and psoriasis: A narrative mini-review and perspective","authors":"Georgia Lada","doi":"10.1016/j.bbih.2025.100949","DOIUrl":"10.1016/j.bbih.2025.100949","url":null,"abstract":"<div><div>Evidence suggests a bidirectional association between psoriasis and depression, which is considered to reflect complex neuroimmunological and psychosocial interactions. Despite an early interest in the brain-skin axis and the role of stress in psoriasis immunopathogenesis, there is ongoing limited preclinical and clinical research into the inflammatory links between depression and psoriasis. Existing findings for serum inflammatory markers of depression in psoriasis are inconsistent and do not fully align with those in the general population, while brain imaging evidence is scarce and has not confirmed direct brain involvement in the systemic inflammation of psoriasis. The present paper reviews the available literature on the immune interplay of psoriasis with depression, highlights the significance of further work in the field and proposes avenues for future research.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100949"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144335","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":"Serum proteomic correlates of mental health symptoms in a representative UK population sample","authors":"Anna Dearman ,&nbsp;Yanchun Bao ,&nbsp;Leonard Schalkwyk ,&nbsp;Meena Kumari","doi":"10.1016/j.bbih.2025.100947","DOIUrl":"10.1016/j.bbih.2025.100947","url":null,"abstract":"<div><div>Poor mental health constitutes a public health crisis due to its high prevalence, unmet need and its mechanistic heterogeneity. A comprehensive understanding of the biological correlates of poor mental health in the population could enhance epidemiological research and eventually help guide treatment strategies. The human bloodstream contains many proteins, several of which have been linked to diagnosed mental health conditions but not to population mental health symptoms, however recent technological advances have made this possible. Here we perform exploratory factor analyses of 184 proteins from two panels (cardiometabolic and neurology-related) measured using proximity extension assays from Understanding Society (the UK Household Longitudinal Study; UKHLS). Data reduction results in 28 factors that explain 55–59% of the variance per panel. We perform multiple linear regressions in up to 5304 participants using two mental health symptom-based outcomes: psychological distress assessed with the general health questionnaire (GHQ-12) and mental health functioning assessed with the 12-Item Short Form Survey, Mental Component Summary (SF12-MCS) using the proteomic factors as explanatory variables and adjusting for demographic covariates. We use backward selection to discard non-significant proteomic factors from the models. Ten factors are independently associated with population mental health symptoms, three of which are immune-related (immunometabolism, immune cell-mediated processes, acute phase processes), three brain-related (neurodevelopment, synaptic processes, neuroprotective processes), two proteolysis-related (proteolysis &amp; the kynurenine pathway, haemostasis &amp; proteolysis), growth factors &amp; muscle, and oxidative stress &amp; the cytoskeleton. Associations partially overlap across the two outcomes, and a sensitivity analysis excluding people taking antidepressants or other central nervous system medications suggestively implicates some of the factors in treatment-resistant poor mental health. Our findings replicate those of case-control studies and expand these to underlie mental health symptomatology in the adult population. More work is needed to understand the direction of causality in these associations.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100947"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143144337","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":"Acute urinary tract infection elicits bladder afferent hypersensitivity","authors":"Harman Sharma ,&nbsp;Sarah K. Manning ,&nbsp;Natalie E. Stevens ,&nbsp;Georgia Bourlotos ,&nbsp;Feargal J. Ryan ,&nbsp;Cindy Tay ,&nbsp;Sonja Klebe ,&nbsp;Geraint B. Rogers ,&nbsp;David J. Lynn ,&nbsp;Steven L. Taylor ,&nbsp;Luke Grundy","doi":"10.1016/j.bbih.2025.100944","DOIUrl":"10.1016/j.bbih.2025.100944","url":null,"abstract":"","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"44 ","pages":"Article 100944"},"PeriodicalIF":3.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11788684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143123567","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":"Biological sex, microglial signaling pathways, and radiation exposure shape cortical proteomic profiles and behavior in mice","authors":"Alexandra O. Strohm ,&nbsp;Sadie Oldfield ,&nbsp;Eric Hernady ,&nbsp;Carl J. Johnston ,&nbsp;Brian Marples ,&nbsp;M. Kerry O'Banion ,&nbsp;Ania K. Majewska","doi":"10.1016/j.bbih.2024.100911","DOIUrl":"10.1016/j.bbih.2024.100911","url":null,"abstract":"<div><div>Patients receiving cranial radiation therapy experience tissue damage and cognitive deficits that severely decrease their quality of life. Experiments in rodent models show that these adverse neurological effects are in part due to functional changes in microglia, the resident immune cells of the central nervous system. Increasing evidence suggests that experimental manipulation of microglial signaling can regulate radiation-induced changes in the brain and behavior. Furthermore, many studies show sex-dependent neurological effects of radiation exposure. Despite this, few studies have used both males and females to explore how sex and microglial function interact to influence radiation effects on the brain. Here, we used a system levels approach to examine how deficiencies in purinergic and fractalkine signaling, two important microglial signaling pathways, impact brain proteomic and behavioral profiles in irradiated and control male and female mice. We performed a comprehensive analysis of the cortical proteomes from irradiated and control C57BL/6J, P2Y12−/−, and CX3CR1−/− mice of both sexes using multiple bioinformatics methods. We identified distinct proteins and biological processes, as well as behavioral profiles, regulated by sex, genotype, radiation exposure, and their interactions. Disrupting microglial signaling, had the greatest impact on proteomic expression, with CX3CR1−/− mice showing the most distinct proteomic profile characterized by upregulation of CX3CL1. Surprisingly, radiation exposure caused relatively smaller proteomic changes in glial and synaptic proteins, including Rgs10, Crybb1, C1qa, and Hexb. While we observed some radiation effects on locomotor behavior, biological sex as well as loss of P2Y12 and CX3CR1 signaling had a stronger influence on locomotor outcomes in our model. Lastly, loss of P2Y12 and CX3CR1 strongly regulated exploratory behaviors. Overall, our findings provide novel insights into the molecular pathways and proteins that are linked to P2Y12 and CX3CR1 signaling, biological sex, radiation exposure, and their interactions.</div></div>","PeriodicalId":72454,"journal":{"name":"Brain, behavior, & immunity - health","volume":"43 ","pages":"Article 100911"},"PeriodicalIF":3.7,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142745588","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}