Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae
Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae
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DOI：
10.1007/s10162-010-0228-1
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发表时间：
2010-12-01
影响因子：
2.4
通讯作者：
Gagnon, Patricia M.
中科院分区：
文献类型：
--
作者：
Ohlemiller, Kevin K.;Dahl, Ashley R.;Gagnon, Patricia M.
CBA/J和CBA/CaJ两种近交系小鼠几乎可以互换使用，作为听力和耳聋研究的“良好听力”标准。然而，我们最近报道，这两种品系在1岁后分化，使得CBA/CaJ小鼠在高频率下显示出更快速的复合动作电位（CAP）阈值升高（Ohlemiller，Brain Res.1277：70-83，2009）。一个贡献者是耳蜗内电位（EP）进行性下降，仅出现在CBA/CaJ。在这里，我们探讨了阈值和EP差异的细胞基础在老年CBA/J和CBA/CaJ小鼠。在主要发现中，两种菌株都表现出特征性的年龄（CBA/J为18个月，CBA/CaJ为24个月），此时女性的敏感性下降超过男性。听力损失进展中的应变差异不是由于CBA/CaJ中毛细胞损失更大，而是反映了更大的神经元损失，加上侧壁更明显的变化，导致EP下降。虽然男性和女性CBA/CaJ都显示出这些病理，但它们在女性中更明显。一个新的特点，不同的应变是中度损失的外沟细胞（或'根'细胞）的螺旋韧带的上基底转在老年CBA/CaJ小鼠，引起深压痕和空隙的韧带。我们的结论是CBA/CaJ小鼠与CBA/J小鼠在年龄相关的耳蜗病理学方面存在定量和定性差异，并模拟了不同类型的老年性耳聋。
Two inbred mouse strains, CBA/J and CBA/CaJ, have been used nearly interchangeably as 'good hearing' standards for research in hearing and deafness. We recently reported, however, that these two strains diverge after 1 year of age, such that CBA/CaJ mice show more rapid elevation of compound action potential (CAP) thresholds at high frequencies (Ohlemiller, Brain Res. 1277: 70-83, 2009). One contributor is progressive decline in endocochlear potential (EP) that appears only in CBA/CaJ. Here, we explore the cellular bases of threshold and EP disparities in old CBA/J and CBA/CaJ mice. Among the major findings, both strains exhibit a characteristic age (similar to 18 months in CBA/J and 24 months in CBA/CaJ) when females overtake males in sensitivity decline. Strain differences in progression of hearing loss are not due to greater hair cell loss in CBA/CaJ, but instead appear to reflect greater neuronal loss, plus more pronounced changes in the lateral wall, leading to EP decline. While both male and female CBA/CaJ show these pathologies, they are more pronounced in females. A novel feature that differed sharply by strain was moderate loss of outer sulcus cells (or 'root' cells) in spiral ligament of the upper basal turn in old CBA/CaJ mice, giving rise to deep indentations and void spaces in the ligament. We conclude that CBA/CaJ mice differ both quantitatively and qualitatively from CBA/J in age-related cochlear pathology, and model different types of presbycusis.