Functional Aging of the Inner Ear Sensory Systems in Mouse Models of Age-Related Hearing Loss

Abstract

Age related structural and functional change in the cochlea have been well described and predisposing factors including genetic background, gender, and environmental factors have been identified. To date, nine genetic loci contributing to age related hearing loss (ARHL) have been identified and auditory function has been described in mouse strains carrying these mutations. The effect of these ARHL mutations on the other inner ear modality (vestibular) is poorly understood. The objective of the current study was to characterize and compare age related change in auditory and vestibular function (more specifically macular function) in three strains carrying ARHL mutations (C57BL/6J, CE/J, and NOD NON-H2nb1/LtJ) and one control strain with no known mutations (CBA/CaJ). Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAE) were used to assess cochlear function and vestibular evoked potential (VsEP) was used to assess macular function. The macular organs from young, mid-life, and old animals were harvested, prepared, and imaged using scanning electron microscopy (SEM) and a qualitative comparison of the number and distribution of macular otoconia was made. ABR and VsEP thresholds, peak latencies, and peak to peak amplitudes were quantified. Linear regression, student's T-test, and ANOVA were used to describe and compare auditory and macular function between genders, within strain, and between strains. DPOAE amplitude was plotted as a function of geometric mean frequency for 11 age groups. No statistical analysis was performed on DPOAE data. No significant gender difference was found for auditory or vestibular function in any strain so genders were pooled for further analysis. The intra-strain comparison of auditory and macular sensitivity reveals a significantly different rate of change in the two modalities in all three strains (p<0.0001). Inter-strain comparison of change in macular sensitivity shows that the CBA/CaJ and CE/J strains lose sensitivity at a significantly faster rate than the C57 strain. A comparison of SEM images from young and old mice revealed no apparent qualitative difference in macular otoconia that would explain the observed declines in macular sensitivity.