The changing phenotype of microglia from homeostasis to disease

Luo, Xiao-Guang; Chen, Sheng-Di

The precise origin and cell lineage of microglia has been a long time debate. So far two most important hypotheses for microglial origin have been held: "neuroectodermal" or "myeloid-monocytic". Even though the latter has been more widely accepted now, the neuroectodermal hypothesis remains interesting. Skoff [7] detected "multipotential glia cell" with a rat model of optic nerve degeneration and optic nerve development, these cells were demonstrated to originate from neuroectodermal matrix cells, and Kitamura later confirmed this result by describing a continuous morphological transition between glioblasts and ramified microglia in the developing gray matter of hippocampus [8] . The hematopoietic origin of microglia also received a lot attention, the presence of bone marrow Mac-1 positive cells were demonstrated in the brain of embryonic and adult mice, and these cells were proved to be the progenitors for microglial cells [9] , also transplantation of GFP + mice bone marrow cells in GFP-host mice revealed the presence of many GFP + microglia throughout developing and/or inflamed CNS [10, 11] , which strongly suggest the hematopoietic stem cells as one of the origins for replenishment of microglia in the neuropathology. Additionally due to the high similarity in marker expression and phagocytosis behavior between circulating monocytes and microglia, people speculate the monocytic origin of microglia, and a couple of experiments have been performed to show the appearance of labeled monocytes in the developing [12] or inflamed brain [13] . In many cases, the peripheral macrophages are considered to be the orthologue [14, 15] or backup of microglia and infiltrate the brain to supplement microglia, thus to some extent peripheral macrophages mirror the behavior of microglia in the brain and Monocytederived Macrophages (MDMs) from patients have been used as a substitute of microglia in many studies [16] [17] [18] .