Abstract
BackgroundReactive 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.ResultsHydrogen 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.ConclusionsThese results indicate that inhibition of axonal transport is an early consequence of exposure to ROS and may contribute to subsequent axonal degeneration.
Highlights
Reactive oxygen species (ROS) released by microglia and other inflammatory cells can cause axonal degeneration
Transport characteristics of mitochondria and Golgi-derived vesicles Mitochondria and Golgi-derived vesicles are two principal classes of organelles moved by axonal transport
We analyzed the axonal transport of mitochondria and Golgi-derived vesicles in hippocampal neurons, following expression of suitable GFP-tagged constructs (Figure 1)
Summary
Reactive oxygen species (ROS) released by microglia and other inflammatory cells can cause axonal degeneration. A reduction in axonal transport has 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. Axonal transport is mediated by kinesins and dyneins, motor proteins that use ATP hydrolysis to power their translocation along microtubules [3,4]. Mutations that disrupt kinesin- or dynein-mediated transport lead to human diseases characterized by axonal dysfunction [5], such as some forms of CharcotMarie-Tooth disease [6] and hereditary spastic paraplegia [7].
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