Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases.
BACKGROUND
Reactive oxygen species (ROS) released by microglia and other inflammatory cells can cause axonal degeneration. A reduction in axonal transport has also been implicated as a cause of axonal dystrophies and neurodegeneration, but there is a paucity of experimental data concerning the effects of ROS on axonal transport. We used live cell imaging to examine the effects of hydrogen peroxide on the axonal transport of mitochondria and Golgi-derived vesicles in cultured rat hippocampal neurons.


RESULTS
Hydrogen peroxide rapidly inhibited axonal transport, hours before any detectable changes in mitochondrial morphology or signs of axonal degeneration. Mitochondrial transport was affected earlier and was more severely inhibited than the transport of Golgi-derived vesicles. Anterograde vesicle transport was more susceptible to peroxide inhibition than retrograde transport. Axonal transport partially recovered following removal of hydrogen peroxide and local application of hydrogen peroxide inhibited transport, suggesting that the effects were not simply a result of nerve cell death. Sodium azide, an ATP synthesis blocker, had similar effects on axonal transport, suggesting that ATP depletion may contribute to the transport inhibition due to hydrogen peroxide.


CONCLUSIONS
These results indicate that inhibition of axonal transport is an early consequence of exposure to ROS and may contribute to subsequent axonal degeneration.
Jungers Center for Neurosciences Research, Department of Neurology, Oregon Health & Science University, Portland, Oregon, USA. bankerg@ohsu.edu.
Cheng
C
Fang
Dennis
D
Bourdette
Gary
G
Banker
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006861:Hydrogen Peroxide / Q000633:toxicity; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009410:Nerve Degeneration / Q000503:physiopathology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017382:Reactive Oxygen Species / Q000633:toxicity*; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
D016877:Oxidants; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide