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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 effe...

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Autores principales: Fang, Cheng, Bourdette, Dennis, Banker, Gary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407799/
https://www.ncbi.nlm.nih.gov/pubmed/22709375
http://dx.doi.org/10.1186/1750-1326-7-29
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author Fang, Cheng
Bourdette, Dennis
Banker, Gary
author_facet Fang, Cheng
Bourdette, Dennis
Banker, Gary
author_sort Fang, Cheng
collection PubMed
description 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.
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spelling pubmed-34077992012-07-30 Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases Fang, Cheng Bourdette, Dennis Banker, Gary Mol Neurodegener Research Article 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. BioMed Central 2012-06-18 /pmc/articles/PMC3407799/ /pubmed/22709375 http://dx.doi.org/10.1186/1750-1326-7-29 Text en Copyright ©2012 Fang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Fang, Cheng
Bourdette, Dennis
Banker, Gary
Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title_full Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title_fullStr Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title_full_unstemmed Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title_short Oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
title_sort oxidative stress inhibits axonal transport: implications for neurodegenerative diseases
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3407799/
https://www.ncbi.nlm.nih.gov/pubmed/22709375
http://dx.doi.org/10.1186/1750-1326-7-29
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