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Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons

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Abstract

Although aminoglycoside antibiotics such as kanamycin are widely used clinically to treat life-threatening bacterial infections, ototoxicity remains a significant dose-limiting side effect. The prevailing view is that the hair cells are the primary ototoxic target of aminoglycosides and that spiral ganglion neurons begin to degenerate weeks or months after the hair cells have died due to lack of neurotrophic support. To test the early developmental aspects of this issue, we compared kanamycin-induced hair cell and spiral ganglion pathology in rat postnatal day 3 cochlear organotypic cultures with adult whole cochlear explants. In both adult and postnatal day 3 cultures, hair cell damage began at the base of the cochleae and progressed toward the apex in a dose-dependent manner. In postnatal day 3 cultures, spiral ganglion neurons were rapidly destroyed by kanamycin prior to hair cell loss. In contrast, adult spiral ganglion neurons were resistant to kanamycin damage even at the highest concentration, consistent with in vivo models of delayed SGN degeneration. In postnatal day 3 cultures, kanamycin preferentially damaged type I spiral ganglion neurons, whereas type II neurons were resistant. Spiral ganglion degeneration of postnatal day 3 neurons was associated with upregulation of the superoxide radical and caspase-3-mediated cell death. These results show for the first time that kanamycin is toxic to postnatal day 3 spiral ganglion neurons, but not adult neurons.

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Acknowledgements

Work supported in part by grant from National Institutes of Occupational Safety and Health (R01OH010235)

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Authors and Affiliations

  1. Department of Otolaryngology Head and Neck Surgery, Xiang Ya Hospital, Central South University, Changsha, Hunan, 410013, China

    Kelei Gao, Hong Sun & Richard Salvi

  2. Center for Hearing and Deafness, University at Buffalo, 137 Cary Hall, Buffalo, NY, 14214, USA

    Dalian Ding & Hong Sun

  3. Department of Audiology and Speech-Language Pathology, Asia University, Taichung, Taiwan

    Jerome Roth & Richard Salvi

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  1. Kelei Gao
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  2. Dalian Ding
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  3. Hong Sun
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  5. Richard Salvi
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Correspondence to Richard Salvi.

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Conflict of Interest

Author RS received a grant from Anida Inc., is a paid consultant for CilCare, and serves as unpaid member of the scientific advisory board of Hyperacusis Research, a nonprofit organization. None of these activities are related to the results contained in the manuscript. The authors declare that they do not have any financial conflict of interest with any of the funding agencies supporting this research.

Research Involving Animals

The experimental procedures were approved by the Institutional Animal Care and Use Committee (IACUC) of the University at Buffalo, NY, USA, and conform to the guidelines from the National Institutes of Health, MD, USA.

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Gao, K., Ding, D., Sun, H. et al. Kanamycin Damages Early Postnatal, but Not Adult Spiral Ganglion Neurons. Neurotox Res 32, 603–613 (2017). https://doi.org/10.1007/s12640-017-9773-2

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