Bullen Anwen, Anderson Lucy, Bakay Warren, Forge Andrew
UCL Ear Institute, London, UK WC1X 8EE
UCL Ear Institute, London, UK WC1X 8EE.
Biol Open. 2019 Jan 7;8(1):bio038547. doi: 10.1242/bio.038547.
The prevalence and importance of hearing damage caused by noise levels not previously thought to cause permanent hearing impairment has become apparent in recent years. The damage to, and loss of, afferent terminals of auditory nerve fibres at the cochlear inner hair cell has been well established, but the effects of noise exposure and terminal loss on the inner hair cell are less known. Using three-dimensional structural studies in mice we have examined the consequences of afferent terminal damage on inner hair cell morphology and intracellular structure. We identified a structural phenotype in the pre-synaptic regions of these damaged hair cells that persists for four weeks after noise exposure, and demonstrates a specific dysregulation of the synaptic vesicle recycling pathway. We show evidence of a failure in regeneration of vesicles from small membrane cisterns in damaged terminals, resulting from a failure of separation of small vesicle buds from the larger cisternal membranes.
近年来,由以前认为不会导致永久性听力损伤的噪声水平所引起的听力损伤的患病率及其重要性已变得显而易见。耳蜗内毛细胞处听觉神经纤维传入终末的损伤和丧失已得到充分证实,但噪声暴露和终末丧失对内毛细胞的影响却鲜为人知。我们利用对小鼠的三维结构研究,考察了传入终末损伤对内毛细胞形态和细胞内结构的影响。我们在这些受损毛细胞的突触前区域发现了一种结构表型,该表型在噪声暴露后持续四周,并显示出突触小泡循环途径的特定失调。我们有证据表明,受损终末中小膜池的小泡再生失败,这是由于小泡芽与较大池膜分离失败所致。