Direct association with the vascular basement membrane is a frequent feature of myelinating oligodendrocytes in the neocortex

Abstract

Background Oligodendrocyte lineage cells interact with the vasculature in the gray matter. Physical and functional interactions between blood vessels and oligodendrocyte precursor cells play an essential role in both the developing and adult brain. Oligodendrocyte precursor cells have been shown to migrate along the vasculature and subsequently detach from it during their differentiation to oligodendrocytes. However, the association of mature oligodendrocytes with blood vessels has been noted since the discovery of this glial cell type almost a century ago, but this interaction remains poorly explored. Results Here, we systematically investigated the extent of mature oligodendrocyte interaction with the vasculature in mouse brain. We found that ~ 17% of oligodendrocytes were in contact with blood vessels in the neocortex, the hippocampal CA1 region and the cerebellar cortex. Contacts were made mainly with capillaries and sparsely with larger arterioles or venules. By combining light and serial electron microscopy, we demonstrated that oligodendrocytes are in direct contact with the vascular basement membrane, raising the possibility of direct signaling pathways and metabolite exchange with endothelial cells. During experimental remyelination in the adult, oligodendrocytes were regenerated and associated with blood vessels in the same proportion compared to control cortex, suggesting a homeostatic regulation of the vasculature-associated oligodendrocyte population. Conclusions Based on their frequent and close association with blood vessels, we propose that vasculature-associated oligodendrocytes should be considered as an integral part of the brain vasculature microenvironment. This particular location could underlie specific functions of vasculature-associated oligodendrocytes, while contributing to the vulnerability of mature oligodendrocytes in neurological diseases.

Heterogeneity of perivascular astrocyte endfeet depending on vascular regions in the mouse brain

“…It was recently shown that mature oligodendrocytes in gray matter directly associate with the vascular BM. 43 In this report, ∼17% of oligodendrocytes mainly contact with capillaries, but not with arterioles or venules, in the mouse cerebral cortex, hippocampus, and cerebellum. In this study, we did not observe the MBP oligodendrocyte marker signal on the isolated blood vessels, but our mass spectrometry analysis showed that oligodendrocyte marker proteins, such as Mag, Mog, and Cntn2, were detected in the purified PV-AEF fraction.…”

Single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

“…We also note recent reports by Yang et al 4 on the AD-relevant activity of CR1 within perivascular macrophages (PVM). Given complex reciprocal interactions between oligodendrocytes and the neurovascular unit 66 , 67 , simultaneous evaluation of CR1 and AD GWAS loci in PVM and oligodendrocytes may illuminate a shared mechanism that could explain the observed CNS as well as hematological effects in a parsimonious manner. Further study of whether peripheral CR1 levels are associated with rs679515 in an AD-specific manner may also be an informative direction for future investigation.…”

A public resource of single cell transcriptomes and multiscale networks from persons with and without Alzheimer’s disease

“…We also note recent reports by Yang et al 58 on AD-relevant activity of CR1 within perivascular macrophages (PVM). Given complex reciprocal interactions between oligodendrocytes and the neurovascular unit 59,60 , simultaneous evaluation of CR1 and AD GWAS loci in PVM and oligodendrocytes may illuminate a shared mechanism that could explain the observed CNS as well as hematological effects in a parsimonious manner. Further investigation of whether rs679515 is associated with alterations of peripheral CR1 may also represent a fruitful path for future study.…”