Extracellular zinc and microglial phenotype

Abstract

Microglia are the resident immune cells of the central nervous system (CNS). When activated by tissue injury or other molecules released from damaged cells following CNS disorders such as brain ischemia and multiple sclerosis (MS), microglia retract their ramifications to form an activated amoeboid morphology. Recent studies have demonstrated that activated microglia can exert either pro-inflammatory or anti-inflammatory properties, which is thought to be regulated by factors in the microenvironment. On the other hand, zinc is concentrated in neurons of specific regions of the central nervous system (CNS) including the hippocampus and spinal cord. Massive amounts of zinc are released by neurons under severe conditions in which microglial activation occurs. This article discusses the role of extracellular zinc in regulation of microglial activation in animal models of brain ischemia and MS, as described in recent literatures by our group and the others. In addition, we review that zinc primes microglia via zinc-induced signaling pathway to enhance production of pro-inflammatory cytokines.