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Developmental changes in microglial mobilization are independent of apoptosis in the neonatal mouse hippocampus
Journal article   Peer reviewed

Developmental changes in microglial mobilization are independent of apoptosis in the neonatal mouse hippocampus

Ukpong B Eyo, Samuel A Miner, Joshua A Weiner and Michael E Dailey
Brain, behavior, and immunity, Vol.55, pp.49-59
07/2016
DOI: 10.1016/j.bbi.2015.11.009
PMCID: PMC4864211
PMID: 26576723
url
http://doi.org/10.1016/j.bbi.2015.11.009View
Open Access

Abstract

•Microglia are surveilling cells involved in clearance of apoptotic cells.•In mouse hippocampus, the density of apoptotic bodies peaks around postnatal day 4.•Rates of microglial motility and migration correlate with levels of apoptotic debris.•Yet, loss of apoptosis does not alter microglial cell density, motility or migration.•Factors other than apoptosis regulate developmental changes in microglial motility and migration. During CNS development, microglia transform from highly mobile amoeboid‐like cells to primitive ramified forms and, finally, to highly branched but relatively stationary cells in maturity. The factors that control developmental changes in microglia are largely unknown. Because microglia detect and clear apoptotic cells, developmental changes in microglia may be controlled by neuronal apoptosis. Here, we assessed the extent to which microglial cell density, morphology, motility, and migration are regulated by developmental apoptosis, focusing on the first postnatal week in the mouse hippocampus when the density of apoptotic bodies peaks at postnatal day 4 and declines sharply thereafter. Analysis of microglial form and distribution in situ over the first postnatal week showed that, although there was little change in the number of primary microglial branches, microglial cell density increased significantly, and microglia were often seen near or engulfing apoptotic bodies. Time-lapse imaging in hippocampal slices harvested at different times over the first postnatal week showed differences in microglial motility and migration that correlated with the density of apoptotic bodies. The extent to which these changes in microglia are driven by developmental neuronal apoptosis was assessed in tissues from BAX null mice lacking apoptosis. We found that apoptosis can lead to local microglial accumulation near apoptotic neurons in the pyramidal cell body layer but, unexpectedly, loss of apoptosis did not alter overall microglial cell density in vivo or microglial motility and migration in ex vivo tissue slices. These results demonstrate that developmental changes in microglial form, distribution, motility, and migration occur essentially normally in the absence of developmental apoptosis, indicating that factors other than neuronal apoptosis regulate these features of microglial development.
 Migration Apoptosis Mobility Motility Microglia

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