Effect of oxidative stress on microglial activation and iron accumulation

Abstract

Microglia are the glial cell in the central nervous system. They function as resident immune cells in the brain. Microglial activation was an increase in the normal aged brain and also more found in the aged brain with neurodegenerative disease. Activated microglial were found iron accumulation leading to increase ROS generation via the Fenton reaction. Therefore, the increase of microglial activation and iron accumulation is vulnerable to neuronal survival. However, the cause of iron accumulation in the activated microglia still unknown. This study hypothesized that oxidative stress which increases in the aged and neurodegenerative disease brain may cause microglial activation and also accumulate iron. The aim of this study was to investigate the effect of oxidative stress to iron accumulation and microglial activation by exposing in the directly oxidative stress and the indirectly oxidative stress via astrocyte conditioned medium. These data demonstrated that the directly expose oxidative stress to microglia did not induce iron deposition while the indirectly oxidative stress via H2O2 astrocyte conditioned medium induced iron deposition and microglial activation. These microglia evidenced the marker of activated microglia as increased ferritin expression, elevated pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), increased ROS level, and decreased mitochondria membrane potential. In addition, iron accumulation was found in these microglia by interrupting the iron import protein (DMT1), and the iron export protein (FPN). In conclusion, iron accumulation in microglia is a consequence of indirect oxidative stress through astrocyte, not the result of direct oxidative stress.