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Histochemistry and Cell Biology

, Volume 150, Issue 3, pp 281–289 | Cite as

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

  • Shelly C. Y. Lin
  • Peter R. Thorne
  • Gary D. Housley
  • Srdjan M. Vlajkovic
Original Paper

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.

Keywords

Aminoglycoside ototoxicity Cochlear explant Neomycin Sensory hair cells Hook region C57BL/6 mouse 

Notes

Acknowledgements

This study was supported by the Auckland Medical Research Foundation.

Compliance with ethical standards

Conflict of interest

The authors of this article have no conflict of interest to declare.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Shelly C. Y. Lin
    • 1
  • Peter R. Thorne
    • 1
  • Gary D. Housley
    • 2
  • Srdjan M. Vlajkovic
    • 1
  1. 1.Department of Physiology and The Eisdell Moore Centre, Faculty of Medical and Health SciencesThe University of AucklandAucklandNew Zealand
  2. 2.Department of Physiology and Translational Neuroscience Facility, School of Medical SciencesUNSWSydneyAustralia

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