The Complex and Integral Roles of Pericytes Within the Neurovascular Unit in Health and Disease

Sutherland, Brad A.

doi:10.1007/978-3-030-62129-2_2

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“…Pericytes are cells embedded on the walls of capillaries throughout the body (Brown et al, 2019 ; Sutherland, 2021 ) and are well characterized as modulators of cerebral blood flow (CBF) (Hall et al, 2014 ). However, little is known about the relationship between microglia and pericytes.…”

Section: Introductionmentioning

confidence: 99%

Microglia directly associate with pericytes in the central nervous system

Morris

Foster

Courtney

et al. 2023

Glia

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Cerebral blood flow (CBF) is important for the maintenance of brain function and its dysregulation has been implicated in Alzheimer's disease (AD). Microglia associations with capillaries suggest they may play a role in the regulation of CBF or the bloodbrain-barrier (BBB). We explored the relationship between microglia and pericytes, a vessel-resident cell type that has a major role in the control of CBF and maintenance of the BBB, discovering a spatially distinct subset of microglia that closely associate with pericytes. We termed these pericyte-associated microglia (PEM). PEM are present throughout the brain and spinal cord in NG2DsRed Â CX 3 CR1 +/GFP mice, and in the human frontal cortex. Using in vivo two-photon microscopy, we found microglia residing adjacent to pericytes at all levels of the capillary tree and found they can maintain their position for at least 28 days. PEM can associate with pericytes lacking astroglial endfeet coverage and capillary vessel width is increased beneath pericytes with or without an associated PEM, but capillary width decreases if a pericyte loses a PEM. Deletion of the microglia fractalkine receptor (CX 3 CR1) did not disrupt the association between pericytes and PEM. Finally, we found the proportion of microglia that are PEM declines in the superior frontal gyrus in AD. In summary, we identify microglia that specifically associate with pericytes and find these are reduced in number in AD, which may be a novel mechanism contributing to vascular dysfunction in neurodegenerative diseases.

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Section: Introductionmentioning

confidence: 99%