Cranial irradiation induces bone marrow-derived microglia in adult mouse brain tissue

Postnatal hematopoietic progenitor cells do not contribute to microglial homeostasis in adult mice under normal conditions. however,previous studies using whole-body irradiation and bone marrow (bm) transplantation models have shown that adult bm cells migrate into the brain tissue and differentiate into microglia (bm-derived microglia; bmdm). here,we investigated whether cranial irradiation alone was sufficient to induce the generation of bmdm in the adult mouse brain. transgenic mice that express green fluorescent protein (gfp) under the control of a murine stem cell virus (mscv) promoter (mscv-gfp mice) were used. mscv-gfp mice express gfp in bm cells but not in the resident microglia in the brain. therefore,these mice allowed us to detect bm-derived cells in the brain without bm reconstitution. mscv-gfp mice,aged 8-12 weeks,received 13.0 gy irradiation only to the cranium,and bm-derived cells in the brain were quantified at 3 and 8 weeks after irradiation. no bm-derived cells were detected in control non-irradiated mscv-gfp mouse brains,but numerous gfp-labeled bm-derived cells were present in the brain stem,basal ganglia and cerebral cortex of the irradiated mscv-gfp mice. these bm-derived cells were positive for iba1,a marker for microglia,indicating that gfp-positive bm-derived cells were microglial in nature. the population of bmdm was significantly greater at 8 weeks post-irradiation than at 3 weeks post-irradiation in all brain regions examined. our results clearly show that cranial irradiation alone is sufficient to induce the generation of bmdm in the adult mouse. © 2014 the author.