Diaz-Aparicio, I. 1, 2 , Abiega, O. 1, 2 & Sierra, A. 3, 1, 2
1 Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, 48170 Zamudio, Spain
2 Department of Neurosciences, University of the Basque Country, 48940 Leioa, Spain
3 Ikerbasque Foundation, 48011 Bilbao, Spain
During neurogenesis in the adult hippocampus, a large part of the newborn cells die by apoptosis. To prevent disturbance of surrounding neurons, apoptotic cells are quickly and effectively removed by phagocytosis by resident microglia. We hypothesize that phagocytic microglia contribute to maintaining the balance of adult hippocampal neurogenic cascade by producing neurogenic factors. To test this hypothesis, we analyzed the expression of neurogenic factors produced by cultured microglia after feeding them with apoptotic NE4C (a mouse neuroprogenitor line) or SH-Y5Y (a human neuronal line) cells. Our data shows that when given apoptotic NE4C cells, 90% of microglia were already phagocytosing within the first hour. Otherwise, for the SH-Y5Y cells, microglia could not reach this percentage until 15 hours, probably due to the need of unconventional recognition mechanisms to phagocytose human apoptotic cells. Moreover, we analyzed different factors secreted by microglia during the assay and found that all of them underwent changes in their expression pattern. To account for possible differences between postnatal and adult microglia, as well as in vivo and in vitro, results were also validated in FACS-purified microglia from dentate gyrus of the adult hippocampus (1-month-old), where apoptosis and phagocytosis are abundant, and CA and cortex, where apoptosis or phagocytosis barely occurs. In conclusion, this could be the first step to elucidate whether the neurogenic cascade is regulated by microglia.