Central Nervous System Developmental Regulation of Microglia via Cytokines and Chemokines

Abstract

Microglia are immune cells resident in the central nervous system (CNS). It has been gradually clarified that microglia play various roles at the developmental stage of the CNS. From embryonic to early postnatal age, microglia remove apoptotic cells by phagocytosis and refine the neural circuits by synaptic pruning. In addition, microglia promote the proliferation and differentiation of neural stem cells by releasing physiologically active substances. Our group has focused on the physiological actions of microglia via cytokines and chemokines at the early postnatal developmental stage. We found that a large number of activated microglia accumulate in the early postnatal subventricular zone (SVZ). We demonstrated that the these SVZ microglia facilitate neurogenesis and oligodendrogenesis via inflammatory cytokines including IL-1β, TNFα, IL-6, IFNγ. We have also found that microglia regulate the functional maturation of the blood brain barrier (BBB) and identified the cytokines and chemokines involved in the effects of microglia. These findings indicate that microglia are physiologically more important than ever thought to reveal robust brain functions. Furthermore, the new mode of microglial action may lead to the discovery of drug targets of the incurable CNS diseases.