Microglia directly associate with pericytes in the central nervous system

Area of Science:

• Neuroscience
• Cell Biology
• Vascular Biology

Background:

• Cerebral blood flow (CBF) is crucial for brain function, and its disruption is linked to Alzheimer's disease (AD).
• Microglia, the brain's immune cells, interact with capillaries, hinting at a role in regulating CBF and the blood-brain barrier (BBB).
• Pericytes are key regulators of CBF and BBB integrity, residing within blood vessel walls.

Purpose of the Study:

• To investigate the relationship between microglia and pericytes.
• To identify and characterize a specific subset of microglia associated with pericytes.

Main Methods:

• Utilized NG2DsRed × CX3CR1+/GFP mice for in vivo imaging.
• Employed two-photon microscopy to observe microglia-pericyte interactions in live animals.
• Examined human frontal cortex tissue to confirm the presence of these cell types.

Main Results:

• Identified a distinct population of pericyte-associated microglia (PEM) throughout the brain and spinal cord in mice and humans.
• PEM maintain stable associations with pericytes for extended periods (≥28 days).
• PEM association influences capillary width, and their numbers are reduced in the superior frontal gyrus of Alzheimer's disease patients.

Conclusions:

• Pericyte-associated microglia (PEM) represent a novel cell subset with a specific spatial relationship to pericytes.
• The reduction of PEM in Alzheimer's disease suggests a potential mechanism contributing to neurovascular dysfunction in AD.
• This finding opens new avenues for understanding microglia's role in maintaining brain health and disease.