When donor microglia are injected into the brain of an adult mouse, the new cells don’t disperse, but remain close to the injection site.
Here, we see 2000 GFP-labeled donor microglia 7 days following injection into a new host. Absent a driving force, they have no stimulus to leave the immediate injection site.
One means of providing a driving force to induce dispersion is to ablate the host population of microglia. This can be accomplished by irradiating the brain, or through inhibition of CSF1R. CSF-1, or Colony Stimulating Factor 1, is a cytokine that is essential for the survival of microglia and other myeloid lineage cells. When CSF-1 is removed or its receptors inhibited, microglia undergo apoptosis, clearing the niche and providing a driving force for donor microglia to occupy vacancies in the parenchyma. Here, we can see that microglia (red) are virtually eliminated within 28 days by CSF1R inhibition.
When host microglia have been cleared, donor microglia are able to proliferate and quickly disperse throughout the brain. Here we see the result of an injection of 2000 GFP-labeled microglia following elimination of host microglia using CSF1R inhibition. Cells have multiplied and re-tiled the brain several millimeters from the injection site, traversing into the hippocampus and contralateral hemisphere.
