衰老小鼠耳蜗内毛细胞及其传出神经支配的生物物理形态学变化。

The Journal of Physiology Pub Date : 2021-01-01 Epub Date: 2020-11-17 DOI:10.1113/JP280256
Jing-Yi Jeng, Adam J Carlton, Stuart L Johnson, Steve D M Brown, Matthew C Holley, Michael R Bowl, Walter Marcotti
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引用次数: 0

摘要

重点:年龄相关性听力损失是一种涉及环境和遗传因素的进行性听力损失,导致听力灵敏度、阈值和言语辨别能力下降。我们比较了四种不同程度进行性听力损失的小鼠内毛细胞(IHCs)的年龄相关变化。耳蜗区9 ~ 12 kHz尖圈IHCs的表面积随年龄增长而减少约30 ~ 40%。在大多数小鼠品系的IHCs中,BK通道的数量随着年龄的增长而逐渐减少,但基底外侧膜电流分布保持不变。携带Cdh23等位基因Cdh23ahl (C57BL/6J;C57BL/6NTac),但在cdh23修复小鼠(C57BL/6NTacCdh23+)中没有,表明它可能导致不同品系小鼠听力损失的不同进展。在不同的小鼠品系中,老年ihc上的传出神经重新布线的程度与听力损失相关,最可能来自侧耳蜗纤维。摘要:内毛细胞是哺乳动物耳蜗的主要感觉受体,可将听觉信息转化为电信号,传递给传入神经元。ihc的功能改变是老年性听力损失的潜在原因。在这里,我们研究了早发性听力损失小鼠携带等位基因Cdh23ahl (C57BL/6J和C57BL/6NTac)、晚发性听力损失小鼠(C3H/HeJ)和纠正了Cdh23ahl突变(C57BL/6NTacCdh23+)并具有中间听力表型的ihc的功能特征。在至少15个月龄之前,耳蜗9-12 kHz区域的ihc没有明显的损失,但从6个月龄开始,它们的表面积逐渐减少了30-40%。虽然BK电流的大小随着年龄的增长而减小,但IHCs保持正常的KCNQ4电流和静息膜电位。C57BL/6J和C57BL/6NTac小鼠的基底外侧膜变化最为严重,C57BL/6NTacCdh23+小鼠的基底外侧膜变化较轻,C3H/HeJ小鼠的基底外侧膜变化最小或不存在。我们还发现,侧耳蜗(LOC)传出纤维与衰老的ihc重新形成功能性轴突-体细胞连接,但这仅在C3H/HeJ小鼠中偶见。传出突触后SK2通道的出现早于传出接触的建立,提示ihc可能在LOC-IHC突触的重建中起直接作用。最后,我们发现在携带Cdh23ahl等位基因的小鼠中,来自ihc的机电换能器(MET)电流的大小随着年龄的增长而显着下降,而在C57BL/6NTacCdh23+小鼠中则没有,这表明MET装置直接导致了年龄相关性听力损失的进展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Biophysical and morphological changes in inner hair cells and their efferent innervation in the ageing mouse cochlea.

Key points: Age-related hearing loss is a progressive hearing loss involving environmental and genetic factors, leading to a decrease in hearing sensitivity, threshold and speech discrimination. We compared age-related changes in inner hair cells (IHCs) between four mouse strains with different levels of progressive hearing loss. The surface area of apical coil IHCs (9-12 kHz cochlear region) decreases by about 30-40% with age. The number of BK channels progressively decreases with age in the IHCs from most mouse strains, but the basolateral membrane current profile remains unchanged. The mechanoelectrical transducer current is smaller in mice harbouring the hypomorphic Cdh23 allele Cdh23ahl (C57BL/6J; C57BL/6NTac), but not in Cdh23-repaired mice (C57BL/6NTacCdh23+ ), indicating that it could contribute to the different progression of hearing loss among mouse strains. The degree of efferent rewiring onto aged IHCs, most likely coming from the lateral olivocochlea fibres, was correlated with hearing loss in the different mouse strains.

Abstract: Inner hair cells (IHCs) are the primary sensory receptors of the mammalian cochlea, transducing acoustic information into electrical signals that are relayed to the afferent neurons. Functional changes in IHCs are a potential cause of age-related hearing loss. Here, we have investigated the functional characteristics of IHCs from early-onset hearing loss mice harbouring the allele Cdh23ahl (C57BL/6J and C57BL/6NTac), from late-onset hearing loss mice (C3H/HeJ), and from mice corrected for the Cdh23ahl mutation (C57BL/6NTacCdh23+ ) with an intermediate hearing phenotype. There was no significant loss of IHCs in the 9-12 kHz cochlear region up to at least 15 months of age, but their surface area decreased progressively by 30-40% starting from ∼6 months of age. Although the size of the BK current decreased with age, IHCs retained a normal KCNQ4 current and resting membrane potential. These basolateral membrane changes were most severe for C57BL/6J and C57BL/6NTac, less so for C57BL/6NTacCdh23+ and minimal or absent in C3H/HeJ mice. We also found that lateral olivocochlear (LOC) efferent fibres re-form functional axon-somatic connections with aged IHCs, but this was seen only sporadically in C3H/HeJ mice. The efferent post-synaptic SK2 channels appear prior to the establishment of the efferent contacts, suggesting that IHCs may play a direct role in re-establishing the LOC-IHC synapses. Finally, we showed that the size of the mechanoelectrical transducer (MET) current from IHCs decreased significantly with age in mice harbouring the Cdh23ahl allele but not in C57BL/6NTacCdh23+ mice, indicating that the MET apparatus directly contributes to the progression of age-related hearing loss.

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