Microglia, the resident immune cells of the brain, were seen to change throughout the lifespan of mice in a study — and to be diverse, with distinct cell subtypes. Those with pro-inflammatory behavior may be disease-causing, as they were found to accumulate in the brains of a mouse model of multiple sclerosis and brain tissue from MS patients.
These results open new possibilities for targeted treatments to enhance microglia’s protective properties, and to block microglia cells that promote MS and other diseases.
The study, “Single-Cell RNA Sequencing of Microglia throughout the Mouse Lifespan and in the Injured Brain Reveals Complex Cell-State Changes” was published in the journal Immunity.
Microglia comprises 10 percent of all brain cells, and are known to respond rapidly to changes in their environment. They are one of the dominant cell types found in MS lesions, and their presence is associated with damage to nerve fibers (axons) and the loss of the protective myelin sheath (a hallmark of MS).
However, whether all microglia cells are the same or whether they are heterogeneous, i.e., they exist as sub-populations, remained unknown.
“Up until now, we didn’t have a good way of classifying microglia. We could only say how branched they look, how dense they look under a microscope,” Timothy Hammond, the study’s first author and a research fellow in neurology at Harvard Medical School and Boston Children’s Hospital, said in a press release.
“We wanted to get an idea of what microglia were doing and ‘thinking,’” he added.
Hammond and colleagues at Harvard investigated the potential heterogeneity within microglia cells of mice. For that, they analyzed the RNA content — RNA is the chemical cousin of DNA — of individual microglia cells in the mouse brain throughout the animals’ lifespan (starting before birth and through to death), as well after acute brain injury.