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

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• 作者：Ke Liu (1)
  Xuejun Jiang (2)
  Chuang Shi (2)
  Lei Shi (2)
  Bo Yang (2)
  Lin Shi (2)
  Yice Xu (1)
  Weiyan Yang (1)
  Shiming Yang (1)
  
• 关键词：Inner hair cells ; Ribbon synapse ; Gentamicin ototoxicity ; Synaptic plasticity ; Cochlea ; Mice
• 刊名：Molecular Neurobiology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：48
• 期：3
• 页码：647-654
• 全文大小：
• 作者单位：Ke Liu (1)
  Xuejun Jiang (2)
  Chuang Shi (2)
  Lei Shi (2)
  Bo Yang (2)
  Lin Shi (2)
  Yice Xu (1)
  Weiyan Yang (1)
  Shiming Yang (1)
  
  1. Department of Otolaryngology?ead and neck surgery, General Hospital of PLA and the E.N.T Institute of PLA, 28 Fuxing Road, Beijing, 100853, China
  2. Department of Otolaryngology?ead and neck surgery, The First Affiliated Hospital of China Medical University, Shenyang, 11001, China
  
• ISSN：1559-1182

文摘

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.