Physiological and injury-induced microglial dynamics across the lifespan

Abstract

Microglia are brains resident immune cells known for their dynamic responses to tissue and vascular injury. Little is known about how microglial activity differs across the life-stages of early development, adulthood, and aging. Using two-photon live imaging, we show that microglia in the adult cerebral cortex exhibit highly ramified processes and relatively immobile somata under basal conditions. Their responses to injury occur over minutes and are highly coordinated neighboring microglia. In neonates, microglia are denser and more mobile but less morphologically complex. Their responses to focal laser-induced injuries of capillaries or parenchymal tissue are uncoordinated, delayed and persistent over days. In the aged brain, microglia somata remain immobile under basal conditions but their processes become less ramified. Their responses to focal injuries remain coordinated but are slower and less sensitive. These studies confirm that microglia undergo significant changes in their morphology, distribution, dynamics and response to injury across the lifespan. HIGHLIGHTSO_LIMicroglia undergo significant morphological and dynamic changes between life-stages. C_LIO_LINeonatal microglia are highly dynamic, less morphologically complex and mount delayed responses to focal injury compared to adult microglia. C_LIO_LIAged microglia are slightly less ramified and their responses to focal injury are slow and less sensitive than adult microglial. C_LIO_LIMaturation of microglial morphology in the developing cortex is disrupted by focal laser injury. C_LI O_FIG O_LINKSMALLFIG WIDTH=163 HEIGHT=200 SRC="FIGDIR/small/615212v1_ufig1.gif" ALT="Figure 1"> View larger version (47K): org.highwire.dtl.DTLVardef@1ba9011org.highwire.dtl.DTLVardef@1485428org.highwire.dtl.DTLVardef@18d1f2aorg.highwire.dtl.DTLVardef@1f9086d_HPS_FORMAT_FIGEXP M_FIG C_FIG