Microglia: Lifelong patrolling immune cells of the brain

Abstract

Microglial cells are the predominant parenchymal immune cell of the brain. Recent evidence suggests that like peripheral immune cells, microglia patrol the brain in health and disease. Reviewing these data, we first examine the evidence that microglia invade the brain mesenchyme early in embryonic development, establish residence therein, proliferate and subsequently maintain their numbers throughout life. We, then, summarize established and novel evidence for microglial process surveillance in the healthy and injured brain. Finally, we discuss emerging evidence for microglial cell body dynamics that challenge existing assumptions of their sessile nature. We conclude that microglia are long-lived immune cells that patrol the brain through both cell body and process movements. This recognition has significant implications for neuroimmune interactions throughout the animal lifespan.

Keywords: Epilepsy; Microglia; Microglial landscape; Neuroimmune interaction; Surveillance.

Figure 1:. Microglial brain colonization and maintenance.

Microglia colonize the developing brain by a combination of migratory invasion and proliferation. While microglia originate predominantly from the embryonic yolk sac, there is some lingering debate as to whether some microglia originate from an alternative source during development. In the mature brain, the microglial population is maintained by a coupling of proliferative expansion and reductive apoptosis.

Figure 2:. Microglial process dynamics in the brain.

Microglial processes are very active during basal surveillance of the brain tissue. This surveillance is controlled by THIK-1 potassium channels. In response to an acute injury, microglial processes move towards the ATP/ADP source through P2Y12Rs to protect the brain from the injury. Especially during conditions of hyperactivity, NMDAR activation of neurons is coupled to the release of ATP/ADP through (an) unidentified channel(s) that recruits microglia through its P2Y12Rs.

Figure 3:. Patrolling microglia in the developing and mature brain.

Microglia exhibit cell body translocations (patrol) in the healthy developing (left) and mature (right) brain. These cells display varying levels of patrol from relatively stationary cells (red cells) to cells with limited cell body translocations (yellow cells) to cells with very significant cell body translocations (green cells). In the developing brain, microglial cell body travel distances are detectable on an minute to hourly basis while in the mature brain detectable travel distances can be observed only on a daily to weekly basis. Changes to the adult patrol levels can be induced by experimental manipulations such as seizures and whisker trimming.