Heterogeneity and developmental dynamics of LYVE-1 perivascular macrophages distribution in the mouse brain

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.

Automated summary

This study investigates the distribution and characteristics of LYVE-1(+) PVMs in the mouse brain. The researchers found that LYVE-1(+) PVMs associate with blood vessels in different patterns depending on vessel diameter and arterio-venous differentiation. The density of LYVE-1(+) PVMs is reduced in an Alzheimer's Disease mouse model in proportion to beta-amyloid deposits. These findings suggest that LYVE-1(+) PVMs play important roles in brain development and regulating brain functions in disease conditions.