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Open Access 01-01-2015 | Original Paper

Mitochondrial fission augments capsaicin-induced axonal degeneration

Authors: Hao Chiang, Nobuhiko Ohno, Yu-Lin Hsieh, Don J. Mahad, Shin Kikuchi, Hitoshi Komuro, Sung-Tsang Hsieh, Bruce D. Trapp

Published in: Acta Neuropathologica | Issue 1/2015

Abstract

Capsaicin, an agonist of transient receptor potential vanilloid receptor 1, induces axonal degeneration of peripheral sensory nerves and is commonly used to treat painful sensory neuropathies. In this study, we investigated the role of mitochondrial dynamics in capsaicin-induced axonal degeneration. In capsaicin-treated rodent sensory axons, axonal swellings, decreased mitochondrial stationary site length and reduced mitochondrial transport preceded axonal degeneration. Increased axoplasmic Ca²⁺ mediated the alterations in mitochondrial length and transport. While sustaining mitochondrial transport did not reduce axonal swellings in capsaicin-treated axons, preventing mitochondrial fission by overexpression of mutant dynamin-related protein 1 increased mitochondrial length, retained mitochondrial membrane potentials and reduced axonal loss upon capsaicin treatment. These results establish that mitochondrial stationary site size significantly affects axonal integrity and suggest that inhibition of Ca²⁺-dependent mitochondrial fission facilitates mitochondrial function and axonal survival following activation of axonal cationic channels.

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Title: Mitochondrial fission augments capsaicin-induced axonal degeneration
Authors: Hao Chiang
Nobuhiko Ohno
Yu-Lin Hsieh
Don J. Mahad
Shin Kikuchi
Hitoshi Komuro
Sung-Tsang Hsieh
Bruce D. Trapp
Publication date: 01-01-2015
Publisher: Springer Berlin Heidelberg
Published in: Acta Neuropathologica / Issue 1/2015
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI: https://doi.org/10.1007/s00401-014-1354-3

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Mitochondrial fission augments capsaicin-induced axonal degeneration

Abstract

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Abstract

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