Sex and interferon gamma signalling regulate microglia migration in adult mouse cortex in vivo

Abstract

Although microglia possess the unique ability to migrate, whether mobility is evident in all microglia, is sex dependent, and what molecular mechanisms drive this, is poorly understood in the adult brain. Using longitudinal in vivo imaging of sparsely labelled microglia, we find a relatively small population of microglia are mobile under normal conditions. Following injury (microbleed), the population of mobile microglia increased in a sex-dependent manner, with male microglia migrating significantly greater distances towards the microbleed relative to their female counterparts. To understand the signaling pathways involved, we interrogated the role of interferon gamma (IFN{gamma}). Our data show that in male mice, stimulating microglia with IFN{gamma} or inducible microglial specific knockdown of IFN{gamma} receptor 1 stimulates or inhibits migration, respectively, whereas female microglia were generally unaffected. These findings highlight the diversity of microglia migratory responses to injury, its dependence on sex and the signaling mechanisms that modulate this behavior.