Age-Related Changes in Cochlear Endolymphatic Potassium and Potential in CD-1 and CBA/CaJ Mice

Abstract

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-1 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-1 mice, as well as a basalward decline of spiral ganglion neuron density. The pathological changes in spiral ligament of CD-1 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.

Age-related auditory pathology in the CBA/J mouse

“…6), in good agreement with previous studies in this and other mouse strains (Sadanaga and Morimitsu, 1995;Wu and Marcus, 2003;Ohlemiller and Gagnon, 2007b). There was no decline with age and EP remained high even in animals with severe elevations in ABR threshold.…”

Apical‐to‐basal gradients in age‐related cochlear degeneration and their relationship to “primary” loss of cochlear neurons

“…Our measures of CAP thresholds and endocochlear potentials, as well as neuronal and hair cell counts, are generally consonant with previous reports in mice (Keithley, 1982;Spongr et al, 1997;Willott et al, 1998;Yoshida et al, 2000;Ding et al, 2001;Hequembourg and Liberman, 2001;Hirose and Liberman, 2003;Wang et al, 2002;Wu and Marcus, 2003). The value of mouse and other animal models for the study of human ARHL depends on the similarity of their pathology at several levels-from their general features and distribution, to underlying cellular events, to their effect on hearing.…”

Chronic Reduction of Endocochlear Potential Reduces Auditory Nerve Activity: Further Confirmation of an Animal Model of Metabolic Presbyacusis

“…Previous studies in our and other laboratories using gerbil and mouse models have shown that cochlear lateral wall pathology, including the degeneration of strial cells and fibrocytes in the spiral ligament, is a major pathology in aged ears (Schulte and Schmiedt 1992;Spicer et al 1997;Hequembourg and Liberman 2001;Spicer and Schulte 2002;2005;Wu and Marcus 2003;Ohlemiller 2004). The loss or diminished function of the cells in the cochlear lateral wall can lead to disruption of inner ear ion and fluid homeostasis, with a subsequent EP decline.…”