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Mystery Cells

New snapsshots of a little-understood brain cell type

by Sver Aune

The long arms of pericytes (shown in red) appear draped over capillaries in the brain (shown in blue). Image courtesy of Dr. Andy Shih.
The long arms of pericytes (shown in red) appear draped over capillaries in the brain (shown in blue). Image courtesy of Dr. Andy Shih.
 

Pericytes, a little-understood cell type on brain blood vessels, grow into the empty space left when neighboring pericytes die, report scientists at MUSC in the January 2, 2018 issue of Cell Reports. (doi: 10.1016/j.celrep.2017.12.016). Such growth is a kind of brain plasticity that might be harnessed to fight age-related vascular disorders such as Alzheimer’s disease and stroke.

Pericytes die in large numbers during Alzheimer’s disease and stroke, but scientists do not know how many distinct types of pericytes there are or what functions the different types perform, according to Andy Y. Shih, Ph.D., assistant professor in the MUSC Department of Neuroscience and principal investigator on the project. “They’re probably the least understood of the cells that comprise the neurovascular unit, which forms the blood vessel walls in the brain,” said Shih.

Shih is interested in why pericytes appear so vulnerable to Alzheimer’s disease and stroke. In the study, adult mice were genetically modified so that their brain pericytes glowed brightly under a powerful two-photon microscope. Using this technique, Shih and graduate student Andrée-Anne Berthiaume, who performed the experiments, were able to take detailed pictures over several weeks to see what happened to the brain when pericytes were lost.

In live mice, the pericytes were seen as oval cell bodies often located near junctions where two capillaries intersected, with long tentacle-like arms called processes extending outward along the capillaries. These unusual cells blanketed much of the capillaries.

To study what happens when a pericyte is lost, Shih’s team used a precision beam of laser light to ablate — or burn off — a single pericyte at a time. As they ablated more pericytes over time, they observed a curious pattern: over a period of days to weeks, the processes of neighboring pericytes grew to cover the capillaries where pericytes had been ablated. When their neighbors were lost, the surviving pericytes seemed to compensate for the job of keeping capillaries toned, a feature that is essential to maintain healthy blood flow in the brain.

The images captured by Shih’s group of pericytes extending their arms to cover exposed capillaries are the first of their kind. Although these findings show that pericytes can take over the job of supporting capillary tone when a single neighbor is lost, it is still not clear what happens when larger numbers of pericytes die, as they do in Alzheimer’s disease and stroke.

Solving that puzzle could reveal ways to facilitate new pericyte growth, which in turn could combat the type of blood vessel dysfunction observed in Alzheimer’s disease and stroke. The Alzheimer’s Association is funding Shih’s next plans to test the health of blood vessels in the brain when larger numbers of pericytes are ablated.

“Are there ways to augment this plasticity, to protect it and stabilize it if we need to? There are mechanisms driving this that we need to understand,” said Shih.