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Ultrastructural analysis of aminoglycoside-induced hair cell death in the zebrafish lateral line reveals an early mitochondrial response

Authors

  • Kelly N. Owens,

    Corresponding author
    1. Department of Biological Structure, University of Washington, Seattle, Washington 98195
    2. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
    3. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195
    • VM Bloedel Hearing Research Center, Box 357923, University of Washington, Seattle, WA 98195
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  • Dale E. Cunningham,

    1. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
    2. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195
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  • Glen Macdonald,

    1. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
    2. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195
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  • Edwin W. Rubel,

    1. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
    2. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195
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  • David W. Raible,

    1. Department of Biological Structure, University of Washington, Seattle, Washington 98195
    2. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
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  • Remy Pujol

    1. Virginia Merrill Bloedel Hearing Research Center, University of Washington, Seattle, Washington 98195
    2. Department of Otolaryngology-Head and Neck Surgery, University of Washington, Seattle, Washington 98195
    3. INSERM Unit 583, Université Montpellier, INM, Hôpital St. Eloi, BP 74103, Montpellier, 34090 France
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Abstract

Loss of the mechanosensory hair cells in the auditory and vestibular organs leads to hearing and balance deficits. To investigate initial, in vivo events in aminoglycoside-induced hair cell damage, we examined hair cells from the lateral line of the zebrafish, Danio rerio. The mechanosensory lateral line is located externally on the animal and therefore allows direct manipulation and observation of hair cells. Labeling with vital dyes revealed a rapid response of hair cells to the aminoglycoside neomycin. Similarly, ultrastructural analysis revealed structural alteration among hair cells within 15 minutes of neomycin exposure. Animals exposed to a low, 25-μM concentration of neomycin exhibited hair cells with swollen mitochondria, but little other damage. Animals treated with higher concentrations of neomycin (50–200 μM) had more severe and heterogeneous cellular changes, as well as fewer hair cells. Both necrotic-like and apoptotic-like cellular damage were observed. Quantitation of the types of alterations observed indicated that mitochondrial defects appear earlier and more predominantly than other structural alterations. In vivo monitoring demonstrated that mitochondrial potential decreased following neomycin treatment. These results indicate that perturbation of the mitochondrion is an early, central event in aminoglycoside-induced damage. J. Comp. Neurol. 502:522–543, 2007. © 2007 Wiley-Liss, Inc.

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