Origin of microglia

Abstract

This paper reviews the various proposed hypotheses on the origin of microglia. The seminal study of del Rio-Hortega first stated that the cells were derived from the mesodermal pial cells that invaded the brain during embryonic development. Along with this was the description of precursor cells in the yolk sac in early development. Our results in the embryonic mouse brain have shown the occurrence of lectin-labelled precursor cells at the yolk sac that later appeared in the mesenchymal tissue associated with the neuroepithelium where they penetrated the nervous tissue to become the microglia. A second major view has held that microglia are of neuroectodermal origin; the cells either originate from glioblasts or the germinal matrix. Another school of thought is that microglia are derived from blood monocytes. In this connection, circulating monocytes enter the developing brain to assume the form as amoeboid microglia that subsequently evolve to become the ramified microglia. In traumatic brain lesions following an intravenous injection of colloidal carbon as a cytoplasmic marker for monocytes, it was found that carbon-labelled monocytes were the main source of brain macrophages, some of which transformed into microglia during the healing process. In conclusion, our results derived from the normal and altered brain development as well as from experimental lesions tend to favour the view of the monocytic nature of microglia. Recent studies by us also point to the possibility that some microglial cells may arise from the pial mesenchymal macrophages that appear to originate from the yolk sac precursors.

Microglia activation in the extremely preterm human brain

“…The large numbers of microglia in the control PVWM as compared with other areas is consistent with previous studies (14,25,26), in which they were also mainly of amoeboid or intermediate active morphology. Microglia in the preterm PVWM were predominantly Iba1/CD68-immunopositive activated microglia.…”

Thematic review series: Brain Lipids. Cholesterol metabolism in the central nervous system during early development and in the mature animal

“…Presumably, both microglia and apoE are involved in this process of enhanced cholesterol excretion. Microglia, unlike macroglial cells, are derived from bone marrow monocyte precursors (174,175). During the development of the CNS, these microglial cells have been shown to engulf and destroy Purkinje cells undergoing programmed cell death (176).…”

The Activation of P2X7 Receptor Impairs Lysosomal Functions and Stimulates the Release of Autophagolysosomes in Microglial Cells

“…Because the CNS is separate from the rest of the body by the blood-brain barrier, and due to the unavailability of Abs, the microglia must quickly recognize foreign bodies, ingest and digest them, and act as APCs activating T cells before the infectious agents damage the sensitive neural tissue. Since microglia are thought to originate from circulating monocytes and because the monocytes are precursors of macrophages (9), it is reasonable to speculate that both microglia and macrophages may share many of the functional properties including autophagy for immune defense.…”