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Divergent Aging Characteristics in CBA/J and CBA/CaJ Mouse Cochleae

机译:CBA / J和CBA / CaJ小鼠耳蜗的发散老化特征

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摘要

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, ). 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 (∼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.
机译:两种自交小鼠品系CBA / J和CBA / CaJ已几乎互换使用,作为研究听力和耳聋的“良好听力”标准。但是,我们最近报道,这两种品系在1岁后发生了分歧,因此CBA / CaJ小鼠在高频下显示出复合动作电位(CAP)阈值的更快升高(Ohlemiller,Brain Res。1277:70-83, )。一个贡献者是仅在CBA / CaJ中出现的内耳蜗电位(EP)逐渐下降。在这里,我们探索老CBA / J和CBA / CaJ小鼠的阈值和EP差异的细胞基础。在主要发现中,两种菌株均表现出特征性年龄(在CBA / J中约为18个月,在CBA / CaJ中为24个月),当雌性的敏感性超过雄性时。听力丧失进程中的应变差异并不是由于CBA / CaJ中毛发细胞损失增多,而是似乎反映出更大的神经元损失,以及侧壁更明显的变化,导致EP下降。尽管男性和女性CBA / CaJ均显示出这些病理,但在女性中更为明显。品系差异显着的新特征是老CBA / CaJ小鼠上基底转弯螺旋韧带中的外沟细胞(或“根”细胞)适度丢失,在韧带中形成了深凹痕和空隙。我们得出的结论是,CBA / CaJ小鼠在与年龄相关的耳蜗病理学方面在数量和质量上均与CBA / J有所不同,并可以模拟不同类型的老年性耳聋。

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