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Resistance to neomycin ototoxicity in the extreme basal (hook) region of the mouse cochlea

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Abstract

Aminoglycoside ototoxicity results in permanent loss of the sensory hair cells in the mammalian cochlea. It usually begins at the basal turn causing high-frequency hearing loss. Here we describe previously unreported resistance of hair cells to neomycin ototoxicity in the extreme basal (hook) region of the developing cochlea of the C57BL/6 mouse. Organ of Corti explants from mice at postnatal day 3 were incubated (37 °C, 5% CO2) in normal culture medium for 19.5 h prior to and after exposure to neomycin (1 mM, 3 h). To study neomycin uptake in the hair cells, cochlear explants were incubated with Neomycin Texas-red (NTR) conjugate. As expected, exposure to neomycin significantly reduced the survival of inner (IHC) and outer hair cells (OHC). IHC survival rate was high in the apical segment and low in the basal segment. OHC were well preserved in the apical and hook regions, with substantial OHC loss in the basal segment. The NTR uptake study demonstrated that the high survival rate in the extreme basal turn OHC was associated with low NTR uptake. Treatment with a calcium chelator (BAPTA), which disrupts the opening of mechanoelectrical (MET) transduction channels, abolished or reduced NTR uptake in the hair cells throughout the cochlea. This confirmed the essential role of MET channels in neomycin uptake and implied that the transduction channels could be impaired in the hook region of the developing mouse cochlea, possibly as a result of the cadherin 23 mutation responsible for the progressive deafness in C57BL/6 mice.

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Acknowledgements

This study was supported by the Auckland Medical Research Foundation.

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Authors and Affiliations

  1. Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, New Zealand

    Shelly C. Y. Lin, Peter R. Thorne & Srdjan M. Vlajkovic

  2. Department of Physiology and Translational Neuroscience Facility, School of Medical Sciences, UNSW, Sydney, NSW, 2052, Australia

    Gary D. Housley

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  1. Shelly C. Y. Lin
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  2. Peter R. Thorne
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  3. Gary D. Housley
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  4. Srdjan M. Vlajkovic
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Correspondence to Shelly C. Y. Lin.

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Lin, S.C.Y., Thorne, P.R., Housley, G.D. et al. Resistance to neomycin ototoxicity in the extreme basal (hook) region of the mouse cochlea. Histochem Cell Biol 150, 281–289 (2018). https://doi.org/10.1007/s00418-018-1683-8

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  • DOI: https://doi.org/10.1007/s00418-018-1683-8

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