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

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.

Deciphering the heterogeneity of the Lyve1+ perivascular macrophages in the mouse brain

“…The Lyve1 + pvMs were located within the perivascular space around arterioles mainly, but not veins. This confirms a recent study in which Lyve1 + pvMs were detected around Cx40 positive arteries and large EphB4 positive veins 25 .…”

“…Recent studies have characterized pvMs and BAM within and outside the CNS, including the peripheral nervous system 23 , 27 , 28 . Particularly, parenchymal Lyve1 + pvMs were shown to be heterogenous by immunofluorescence on sections 25 .…”

“…In the mouse brain, myeloid cells are a heterogeneous group of cells localized in specific niches and include parenchymal microglia and non-parenchymal pvMs 8 , 24 . Previously, brain pvMs were described to be Lyve1 + CD45 high and were shown to express canonical macrophage markers such as fractalkine receptor (CX3CR1), colony-stimulating factor1 receptor (Csf-1R), CD206, and Iba-1, but also the prototypic macrophage markers CD11b and F4/80 8 , 9 , 25 , 26 .…”

Temporal Pattern of Neuroinflammation Associated with a Low Glycemic Index Diet in the 5xFAD Mouse Model of Alzheimer’s Disease

“…1 ). However, we cannot exclude the possibility that a small percentage of CD11b + cells represents vascular associated macrophages [ 46 ] known to have a role in regulation of vascular amyloid-beta plaques deposition [ 47 ]. Importantly, TNFα + cells co-expressing the CD11b (OX-42) marker represented the vast majority, ranging from 68 to 78%, at all hippocampal layers, in control mice, and at both time points studied.…”

Infiltration of meningeal macrophages into the Virchow–Robin space after ischemic stroke in rats: Correlation with activated PDGFR-β-positive adventitial fibroblasts

“…We first validated two well-known markers for CNS borderassociated macrophages (BAMs): CD206 and lymphatic vessel endothelial hyaluronan receptor 1 (Lyve1; Jordão et al, 2019;Karam et al, 2022;Masuda et al, 2022). Double labeling with either CD206 or Lyve1 and ionized calcium-binding adaptor molecule 1 (Iba1) showed that both markers were present in Iba1-positive macrophage-like phenotype with amoeboid morphology, but they exhibited different degrees of coexistence with Iba1.…”