Age-related changes in cochlear endolymphatic potassium and potential in CD-1 and CBA/CaJ mice
Age-related changes in cochlear endolymphatic potassium and potential in CD-1 and CBA/CaJ mice
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DOI：
10.1007/s10162-002-3026-6
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发表时间：
2003-09-01
影响因子：
2.4
通讯作者：
Marcus, DC
中科院分区：
文献类型：
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作者：
Wu, T;Marcus, DC
已知CD-1小鼠品系具有早发性听力损失，其随着年龄的增长而进行性。我们试图确定是否K稳态和耳蜗外侧壁的病理变化的障碍参与了年龄相关性听力损失（AHL）的CD-1相比，CBA/CaJ株，具有最小的阿勒。在本研究中，使用双管微电极测量了两种小鼠在“年轻”（1-2个月）和“年老”（5-9个月）年龄时的耳蜗内电位（EP）和内淋巴K+浓度（[K+]（e））。CBA/CaJ小鼠的EP和基底转的[K+]（e）无增龄变化。在顶转中，在常氧和急性缺氧条件（-EP）下，随着老化，EP（10 mV）有一个小的正移，而[K+]（e）没有任何变化。CBA/CaJ小鼠外侧壁未见明显病理改变。相比之下，老年CD-1小鼠在基底和顶转中显示出显著降低30%的[K+]（e），而在常氧EP中没有显著变化。在顶转的-EP的幅度显着降低了6 mV。随着年龄的增长，在IV型纤维细胞的顶端和基底转和II型纤维细胞的基底转的区域中观察到细胞的严重损失。在老年CD-1小鼠的基底转处也观察到Corti器的完全变性，以及螺旋神经节神经元密度向基底下降。CD-1小鼠螺旋韧带的病理变化与表达阿勒基因（阿勒）的近交系C57 BL/6 J小鼠相似，可能是CD-1小鼠阿勒的主要病因。这些发现对我们理解阿勒和解释CD-1背景下的基因突变具有重要意义。
The CD-1 mouse strain is known to have early onset of hearing loss that is progressive with aging. We sought to determine whether a disturbance of K homeostasis and pathological changes in the cochlear lateral wall were involved in the age-related hearing loss (AHL) of CD-1 as compared to the CBA/CaJ strain which has minimal AHL. In the present study, the endocochlear potential (EP) and endolymphatic K+ concentration ([K+](e)) were measured in both strains of mice with double-barrel microelectrodes at "young" (1-2 mo) and "old" (5-9 mo) ages. CBA/CaJ mice displayed no changes with aging in EP and [K+](e) of the basal turn. In the apical turn, there was a small positive shift of the EP (10 mV) with aging under both normoxic and acute anoxic conditions (-EP), without any change of [K+](e). Further, there were no obvious pathological changes in the lateral wall of CBA/CaJ mice. By contrast, old CD-I mice displayed a significantly reduced [K+](e) by 30% in both basal and apical turns with no significant changes in normoxic EP. The -EP in the apical turn was significantly reduced in magnitude by 6 mV. A severe loss of cells with aging was observed in the region of type IV fibrocytes of the apical and basal turns and of type II fibrocytes in the basal turn. A complete degeneration of organ of Corti was also observed at the basal turn of old CD-I mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-I mice were similar to those of an inbred mouse strain C57BL/6J that expresses an AHL gene (ahl) and might be a primary etiology of AHL of CD-1 mice. These findings have ramifications for our understanding of AHL and for interpretation of genetic mutations in a CD-1 background.