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Updated: May 29, 2025
Intravital Imaging of Axonal Interactions with Microglia and Macrophages in a Mouse Dorsal Column Crush Injury
Published on: November 23, 2014
CNS resident macrophages exhibit region-specific states and immunogenic responses during Rbpj-deficient brain
Sera Nakisli1,2, Kayleigh Fanelli1,2, Julia LaComb1
1Department of Biological Sciences, Ohio University, 57 Oxbow Trail, Irvine 107, Athens, OH, 45701, USA.
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.
Insights
Microglia, the brain's immune cells, change their state during neurovascular diseases like brain arteriovenous malformations (bAVMs). These changes involve altered cell structure and region-specific gene expression, impacting immune responses.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia are the central nervous system's (CNS) resident immune cells, acting as macrophages.
- During neurovascular diseases, microglia undergo significant state changes in response to neural perturbations.
- These state changes affect their molecular, cellular, and functional properties, impacting CNS health.
Purpose of the Study:
- To investigate the alterations in brain resident macrophage (microglia) states during the pathogenesis of neurovascular disease.
- To utilize a mouse model of brain arteriovenous malformation (bAVM) caused by endothelial Recombination signal binding protein for immunoglobulin kappa J region (Rbpj) deficiency.
Main Methods:
- Employing a mouse model of endothelial Rbpj-deficient bAVM.
- Analyzing tissue for changes in Ionized calcium-binding adapter molecule 1 (Iba1) expression and cell morphology.
- Performing gene expression analysis on isolated microglia from different brain regions.
Main Results:
- Increased Iba1 expression area, cell hypertrophy, number, and proliferation in Rbpj-deficient bAVM tissue.
- Hypertrophic microglia exhibited larger cell bodies and reduced process length, indicating a shift in surveillance state.
- Region-specific gene expression profiles in cortical and cerebellar microglia suggested altered metabolic activity and distinct immune responses (cytokine-associated vs. pathogen-recognition).
Conclusions:
- Rbpj deficiency in endothelial cells triggers significant changes in microglia states within the developing bAVM.
- These microglial state changes are region-specific, with distinct molecular and functional profiles in cortical versus cerebellar regions.
- The study highlights the complex interplay between vascular integrity, Rbpj signaling, and microglial responses in neurovascular disease pathogenesis.
