Molecular effects of activated BV-2 microglia by mitochondrial toxin 1-methyl-4-phenylpyridinium

Microglia plays an important role in inflammation-mediated neurodegeneration. Compelling evidence supports the hypothesis that microglial activation contributes to the pathogenesis of various neurodegenerative diseases. However, little is known about the molecular outcome of activated microglia. In this report, we investigate the molecular consequences of MPP+ toxin-induced activated BV-2 microglia. Intoxication of specific mitochondrial toxin methyl-4-phenylpyridinium iodide ion (MPP+) to BV-2 cells induced significant mitochondrial dysfunction and increased the reactive oxygen species generation, caspase-3 activation, and poly ADP ribose polymerase proteolysis. Further, MAC-1 immunostaining in the midbrain of mice revealed a decrease in activated microglia at day 4 after intoxication with MPP+. From this study, it was confirmed that BV-2 microglia respond to the mitochondrial toxin MPP+ which may lead to apoptotic cell death. Understanding of the mechanistic basis of apoptotic elimination of activated microglia may help to develop new strategies for the treatment of neurodegenerative diseases.

► Activated BV-2 microglial fate under MPP+ stimulation and MPTP intoxication in mice were examined. ► Mitochondrial dysfunction, ROS generation and apoptotic parameters were observed. ► Reduced number of activated microglia at day 4 and 7 was observed upon MPTP intoxication to mice. ► Apoptotic elimination of over-activated microglia might be a primary regulatory mechanism.