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Cochlear Inner Hair Cell Ribbon Synapse is the Primary Target of Ototoxic Aminoglycoside Stimuli

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Abstract

The ribbon synapses of inner hair cells (IHCs) play an important role in sound encoding and neurotransmitter release. However, it remains unclear whether IHC ribbon synapse plasticity can be interrupted by ototoxic aminoglycoside stimuli. Here, we report that quantitative changes in the number of IHC ribbon synapses and hearing loss occur in response to gentamicin treatment in mice. Using 3D reconstruction, we were able to calculate the number of IHC ribbon synapses after ototoxic gentamicin exposure. Mice were injected intraperitoneally with a low dose of gentamicin (100 mg/kg) once a day for 14 days. Double immunostaining was used to identify IHC ribbon synapses; histopathology and scanning electron microscopy were used to observe the morphology of cochlear hair cells and spiral ganglion neurons (SGNs), the hearing threshold shifts were recorded by auditory brainstem response examinations. Our study shows that the maximal number of IHC ribbon synapses appeared at the 7th day after treatment, followed by a significant reduction after the 7th day regardless of ongoing treatment. Correspondingly, the maximal elevation of hearing threshold was observed at the 7th day after treatment. Meanwhile, additional cochlear components included OHCs, IHCs, and SGNs were unaffected, suggesting that IHC ribbon synapses are more susceptible to ototoxic aminoglycoside stimulation. Our study indicated that quantitative changes in the number of IHC ribbon synapses is critical response to lower dose of ototoxic stimulation, and may contribute to moderate hearing loss. Additionally, our data indcated that ribbon synaptic plasticity may require the quantitative changes to play self-protective role adapted to ototoxic aminoglycoside stimuli.

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Acknowledgments

This work was supported by grants from the National Basic Research Program of China (973 Program; 2012CB967900, 2012CB967901, 2011CBA01000), the National Natural Science Foundation of China (NSFC; 30871398, 30730040, 31040038, 81271082). Additionally, this work was also supported by the grants from the China Postdoctoral Science Foundation (201003779, 20100470103), Beijing Natural Science Foundation (5122040), and Fund for Scientific Research of The First Affliliated Hospital of China Medical University (FSFH 1216).

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The authors declare no competing financial interests.

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Authors and Affiliations

  1. Department of Otolaryngology—Head and neck surgery, General Hospital of PLA and the E.N.T Institute of PLA, 28 Fuxing Road, Beijing, 100853, China

    Ke Liu, Yice Xu, Weiyan Yang & Shiming Yang

  2. Department of Otolaryngology—Head and neck surgery, The First Affiliated Hospital of China Medical University, Shenyang, 11001, China

    Xuejun Jiang, Chuang Shi, Lei Shi, Bo Yang & Lin Shi

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  1. Ke Liu
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  2. Xuejun Jiang
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  3. Chuang Shi
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  4. Lei Shi
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  6. Lin Shi
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  7. Yice Xu
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  8. Weiyan Yang
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  9. Shiming Yang
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Correspondence to Shiming Yang.

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Liu, K., Jiang, X., Shi, C. et al. Cochlear Inner Hair Cell Ribbon Synapse is the Primary Target of Ototoxic Aminoglycoside Stimuli. Mol Neurobiol 48, 647–654 (2013). https://doi.org/10.1007/s12035-013-8454-2

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  • DOI: https://doi.org/10.1007/s12035-013-8454-2

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