CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation
Abstract Microglia are heterogeneous macrophage cells that serve as the central nervous system’s resident immune cells. During neuro-related diseases, CNS resident macrophages change their molecular, cellular, and functional properties—that collectively define “states”—in response to specific neural...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-86150-4 |
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| author | Sera Nakisli Kayleigh Fanelli Julia LaComb Lily J. Arnold Corinne M. Nielsen |
| author_facet | Sera Nakisli Kayleigh Fanelli Julia LaComb Lily J. Arnold Corinne M. Nielsen |
| author_sort | Sera Nakisli |
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| description | Abstract Microglia are heterogeneous macrophage cells that serve as the central nervous system’s resident immune cells. During neuro-related diseases, CNS resident macrophages change their molecular, cellular, and functional properties—that collectively define “states”—in response to specific neural perturbations. Neurovascular diseases elicit state changes, by promoting increased vascular permeability among microvessels and thus altering blood–brain barrier integrity. Here, we used a mouse model of brain arteriovenous malformation (bAVM)—mediated by endothelial loss of Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)—to investigate changes to brain resident macrophage states during neurovascular disease pathogenesis. We found increased area of Ionized calcium-binding adapter molecule 1 (Iba1) expression in Rbpj-deficient bAVM tissue, as well as Iba1 + cell hypertrophy, increased cell number, and hyperproliferation within areas of increased Iba1 + density. Hypertrophic cells had increased cell body areas and decreased process length, suggesting a transition in surveillance state. Gene expression data revealed region-specific molecular changes to Iba + cells, suggestive of altered metabolic activity. CNS resident macrophages isolated from cortical and cerebellar regions showed profiles consistent with cytokine-associated immunogenic responses and an immunovigilant pathogen-recognition response, respectively. Thus, our findings demonstrate region-specific changes to CNS resident macrophages during Rbpj-deficient bAVM. |
| format | Article |
| id | doaj-art-e2bac6888bfe4f4b86e827c83bf305ab |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
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| spelling | doaj-art-e2bac6888bfe4f4b86e827c83bf305ab2025-02-02T12:18:52ZengNature PortfolioScientific Reports2045-23222025-01-0115111710.1038/s41598-025-86150-4CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformationSera Nakisli0Kayleigh Fanelli1Julia LaComb2Lily J. Arnold3Corinne M. Nielsen4Department of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityDepartment of Biological Sciences, Ohio UniversityAbstract Microglia are heterogeneous macrophage cells that serve as the central nervous system’s resident immune cells. During neuro-related diseases, CNS resident macrophages change their molecular, cellular, and functional properties—that collectively define “states”—in response to specific neural perturbations. Neurovascular diseases elicit state changes, by promoting increased vascular permeability among microvessels and thus altering blood–brain barrier integrity. Here, we used a mouse model of brain arteriovenous malformation (bAVM)—mediated by endothelial loss of Recombination signal binding protein for immunoglobulin kappa J region (Rbpj)—to investigate changes to brain resident macrophage states during neurovascular disease pathogenesis. We found increased area of Ionized calcium-binding adapter molecule 1 (Iba1) expression in Rbpj-deficient bAVM tissue, as well as Iba1 + cell hypertrophy, increased cell number, and hyperproliferation within areas of increased Iba1 + density. Hypertrophic cells had increased cell body areas and decreased process length, suggesting a transition in surveillance state. Gene expression data revealed region-specific molecular changes to Iba + cells, suggestive of altered metabolic activity. CNS resident macrophages isolated from cortical and cerebellar regions showed profiles consistent with cytokine-associated immunogenic responses and an immunovigilant pathogen-recognition response, respectively. Thus, our findings demonstrate region-specific changes to CNS resident macrophages during Rbpj-deficient bAVM.https://doi.org/10.1038/s41598-025-86150-4BrainMicrogliaMouseRbpjVascular malformationVessel permeability |
| spellingShingle | Sera Nakisli Kayleigh Fanelli Julia LaComb Lily J. Arnold Corinne M. Nielsen CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation Scientific Reports Brain Microglia Mouse Rbpj Vascular malformation Vessel permeability |
| title | CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation |
| title_full | CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation |
| title_fullStr | CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation |
| title_full_unstemmed | CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation |
| title_short | CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain arteriovenous malformation |
| title_sort | cns resident macrophages exhibit region specific states and immunogenic responses during rbpj deficient brain arteriovenous malformation |
| topic | Brain Microglia Mouse Rbpj Vascular malformation Vessel permeability |
| url | https://doi.org/10.1038/s41598-025-86150-4 |
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