NADPH oxidase and microglial activation in 6-0HDA-induced degeneration of dopaminergic neurons

摘要

In mesencephalic cultures, we observed a significant dopaminergic (DA) cell loss 24 h after administration of 6-OHDA, and a significant increase in NADPH subunit expression, microglial activation and reactive oxygen species (ROS) in DA cells, that were significantly decreased by the inhibition of NADPH. In rats, 48 h after 6-OHDA injection there was still no significant loss of DA neurons although there was an increase in microglial activation and NADPH subunit expression. The results suggests that in addition to the autooxidation-derived ROS and a direct inhibition of the mitochondrial respiratory chain, early microglial activation and NADPH-oxidase-derived ROS act synergistically with 6-OHDA and constitute an early component of the 6-OHDA-induced cell death.