Microglia engulf viable newborn cells in the epileptic dentate gyrus.
Microglia, which are the brain's resident immune cells, engulf dead neural progenitor cells during adult neurogenesis in the subgranular zone (SGZ) of the dentate gyrus (DG). The number of newborn cells in the SGZ increases significantly after status epilepticus (SE), but whether and how microglia regulate the number of newborn cells after SE remain unclear. Here, we show that microglia rapidly eliminate newborn cells after SE by primary phagocytosis, a process by which viable cells are engulfed, thereby regulating the number of newborn cells that are incorporated into the DG. The number of newborn cells in the DG was increased at 5 days after SE in the adult mouse brain but rapidly decreased to the control levels within a week. During this period, microglia in the DG were highly active and engulfed newborn cells. We found that the majority of engulfed newborn cells were caspase-negative viable cells. Finally, inactivation of microglia with minocycline maintained the increase in the number of newborn cells after SE. Furthermore, minocycline treatment after SE induced the emergence of hilar ectopic granule cells. Thus, our findings suggest that microglia may contribute to homeostasis of the dentate neurogenic niche by eliminating excess newborn cells after SE via primary phagocytosis. GLIA 2016;64:1508-1517.
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Cong
C
Luo
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Ryuta
R
Koyama
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Japan.
Yuji
Y
Ikegaya
D000818:Animals; D018891:Dentate Gyrus / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006706:Homeostasis / Q000502:physiology; D008297:Male; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism*; D013226:Status Epilepticus / Q000378:metabolism
epilepsy; hippocampus; microglia; neurogenesis; phagocytosis