Related Experiment Video
Updated: Sep 6, 2025
Author Spotlight: Magnetic Bead-Based Isolation of Murine Dermal Lymphatic Endothelial Cells
Published on: July 21, 2023
Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain
Marie Karam1, Hadrien Janbon1, Guy Malkinson1
1Center for Interdisciplinary Research in Biology (CIRB), College de France, CNRS, INSERM, Université PSL, Paris, France.
Abstract:
Brain perivascular macrophages (PVMs) are border-associated macrophages situated along blood vessels in the Virchow-Robin space and are thus found at a unique anatomical position between the endothelium and the parenchyma. Owing to their location and phagocytic capabilities, PVMs are regarded as important components that regulate various aspects of brain physiology in health and pathophysiological states. Here, we used LYVE-1 to identify PVMs in the mouse brain using brain-tissue sections and cleared whole-brains to learn about how they are distributed within the brain and across different developmental postnatal stages. We find that LYVE-1+ PVMs associate with the vasculature in different patterns and proportions depending on vessel diameter or arterio-venous differentiation. LYVE-1+ PVMs relate to blood vessels in a brain-region-dependent manner. We show that their postnatal distribution is developmentally dynamic and peaks at P10-P20 depending on the brain region. We further demonstrate that their density is reduced in the APP/PS1 mouse model of Alzheimer's Disease proportionally to beta-amyloid deposits. In conclusion, our results reveal unexpected heterogeneity and dynamics of LYVE-1+ PVMs, with selective coverage of brain vasculature, compatible with potential unexplored roles for this population of PVMs in postnatal development, and in regulating brain functions in steady-state and disease conditions.
Insights
Brain perivascular macrophages (PVMs) show dynamic distribution patterns in the developing mouse brain. Their density decreases in an Alzheimer's disease model, suggesting roles in brain health and disease.
Area of Science:
- Neuroimmunology
- Macrophage Biology
- Developmental Neuroscience
Background:
- Brain perivascular macrophages (PVMs) are crucial for brain physiology, located uniquely between blood vessels and brain parenchyma.
- Their role in brain function and disease necessitates understanding their distribution and dynamics.
Purpose of the Study:
- To investigate the distribution and developmental dynamics of PVMs in the mouse brain using LYVE-1 as a marker.
- To examine PVM distribution relative to vasculature and brain regions.
- To assess PVM density in an Alzheimer's disease model.
Main Methods:
- Utilized LYVE-1 staining on mouse brain tissue sections and cleared whole-brains.
- Analyzed PVM distribution patterns based on vessel diameter and arterio-venous differentiation.
- Quantified PVM density in wild-type and APP/PS1 mouse models of Alzheimer's Disease.
Main Results:
- LYVE-1+ PVMs exhibit varied associations with brain vasculature, dependent on vessel type and brain region.
- PVM distribution is developmentally dynamic, peaking between postnatal days 10-20 in a region-specific manner.
- PVM density is reduced in APP/PS1 mice, correlating with beta-amyloid deposition.
Conclusions:
- PVMs display significant heterogeneity and dynamic changes in their distribution during postnatal development.
- These findings suggest unexplored roles for PVMs in brain development, homeostasis, and Alzheimer's Disease pathogenesis.
- Selective vascular coverage by PVMs highlights their specialized functions in the central nervous system.
