Age-related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells.
Age-related changes in the biophysical and morphological characteristics of mouse cochlear outer hair cells.
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DOI：
10.1113/jp279795
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发表时间：
2020-09
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影响因子：
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通讯作者：
Marcotti W
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作者：
Jeng JY;Johnson SL;Carlton AJ;De Tomasi L;Goodyear RJ;De Faveri F;Furness DN;Wells S;Brown SDM;Holley MC;Richardson GP;Mustapha M;Bowl MR;Marcotti W
外毛细胞（ohc）是哺乳动物耳蜗内提供声音放大的电运动感觉受体。尽管OHCs易受衰老影响，但对这些细胞的病理生理变化的进展仍知之甚少。通过使用不同听力损失进展的小鼠品系（C57BL/6J, C57BL/6NTac, C57BL/6NTacCdh23+, C3H/HeJ），我们确定了老化OHCs （9-12kHz耳蜗区）的形态学，生理和分子变化。我们发现，到6个月大时，所有菌株的OHCs的表面积都减少了，这不是变性的迹象。尽管老化的OHCs保留了正常的基底外侧膜蛋白结构，但它们显示出K+电流和非线性电容的减小，这是prespresin依赖性电动力的读数。尽管有这些变化，ohc仍有正常的V m，并保留了放大声音的能力，因为老年、听力良好的小鼠的DPOAE阈值没有受到影响（C3H/HeJ, C57BL/6NTacCdh23+）。所有品系在15个月时均出现传入突触的丧失。每个OHCs的传出突触数量（定义为突触后SK2点）在除C3H小鼠外的所有品系的衰老OHCs中都减少了。在所有小鼠品系的老年ohc中都发生了一些已确定的变化，因此代表了与年龄相关的听力损失病理生理进展的一般特征，可能旨在保持功能。我们还发现，携带Cdh23ahl等位基因的小鼠ohc的MET电流随着年龄的增长而减少，这表明MET装置的变化可能在耳蜗老化中发挥作用。
Outer hair cells (OHCs) are electromotile sensory receptors that provide sound amplification within the mammalian cochlea. Although OHCs appear susceptible to ageing, the progression of the pathophysiological changes in these cells is still poorly understood. By using mouse strains with a different progression of hearing loss (C57BL/6J, C57BL/6NTac, C57BL/6NTacCdh23+, C3H/HeJ), we have identified morphological, physiological and molecular changes in ageing OHCs (9-12kHz cochlear region). We show that by 6 months of age, OHCs from all strains underwent a reduction in surface area, which was not a sign of degeneration. Although the ageing OHCs retained a normal basolateral membrane protein profile, they showed a reduction in the size of the K+ current and non-linear capacitance, a readout of prestin-dependent electromotility. Despite these changes, OHCs have a normal V m and retain the ability to amplify sound, as DPOAE thresholds were not affected in aged, good-hearing mice (C3H/HeJ, C57BL/6NTacCdh23+). The loss of afferent synapses was present in all strains at 15 months. The number of efferent synapses per OHCs, defined as post-synaptic SK2 puncta, was reduced in aged OHCs of all strains apart from C3H mice. Several of the identified changes occurred in aged OHCs from all mouse strains, thus representing a general trait in the pathophysiological progression of age-related hearing loss, possibly aimed at preserving functionality. We have also shown that the MET current from OHCs of mice harbouring the Cdh23ahl allele is reduced with age, highlighting the possibility that changes in the MET apparatus could play a role in cochlear ageing.