Evaluating cochlear function and the effects of noise exposure in the B6.CAST+Ahl mouse with distortion product...

Cochlear function and susceptibility to noise over-exposure were examined in the congenic mouse strain B6.CAST+Ahl (B6.CAST) and compared to these same features in the CAST/Ei (CAST) and C57BL/6J (C57) parental strains. For both types of comparisons, the primary measure was the distortion-product otoacoustic emissions (DPOAE) at 2f1-2f2. Our assumption was that the B6.CAST mouse was corrected for the early onset age-related hearing loss (AHL) exhibited by one of its parental strains (C57) by the age-resistant properties of its other parental strain (CAST), and thus would exhibit neither AHL nor susceptibility to noise overstimulation effects. With respect to cochlear function, for 2.5-month mice, there was a tendency for DPOAEs to be slightly lower for mid-frequency primary tones for both C57 and B6.CAST mice, while the former mice showed clear AHL effects at the highest test frequency. However, by 5 months of age, the B6.CAST mice, like the CAST mice, displayed robust DPOAE levels that were significantly larger than DPOAE levels for the C57 mice, which were essentially absent for frequencies above about 30 kHz. To investigate the role of the Ahl gene in the susceptibility of the cochlea to the effects of noise over-exposure, two distinct paradigms consisting of temporary (TTS: 1-min, 105-dB SPL, 10-kHz pure tone) and permanent (PTS: 1-h, 105-dB SPL, 10-kHz octave band noise) threshold-shift protocols were used. The brief TTS exposure produced reversible reductions in DPOAEs that for both the B6.CAST and CAST mice recovered to within a few dB of their baseline levels by 3 min post-exposure. In contrast, the C57 mice recovered somewhat slower and, by 5 min post-exposure, emission levels were still 5 dB or more below their corresponding pre-exposure values. At 3 months of age, the TTS mice along with another group of naïve subjects representing the same three mouse strains were exposed to the PTS paradigm. By 4 days post-exposure, for B6.CAST and CAST mice, DPOAE levels had recovered to their pre-exposure control levels. However, DPOAEs for the C57 mice at most of the measurable frequencies were at least 10-30 dB lower than their counterpart baseline levels. Together these data suggest that the Ahl allele in the C57 strain contributes to both the early onset AHL exhibited by these mice as well as their susceptibility to both TTS and PTS over-exposures.