Genetic influences on susceptibility of the auditory system to aging and environmental factors

Auditory susceptibility to aging and environmental factors (noise and toluene) was investigated in two genotypes of mice, CBA/Ca (showing a moderate hearing loss with onset late in life) and C57BL/6J (undergoing spontaneous auditory degeneration with onset during young adulthood). Both strains of mice were often used together as a model of human age-related hearing loss, with a primary decline in auditory high-frequency sensitivity. Auditory function was analysed by recording auditory brainstem response (ABR). Morphological alterations of mouse cochleae were studied by light, transmission and scanning electron microscopy. The age-related elevation of ABR thresholds was more precipitous and the individual variability was larger in C57BL mice than that in CBA mice. Degeneration patterns of the organ of Corti were different between the two strains. In the old CBA-mouse cochlea, giant stereocilia on the inner hair cells (IHCs) and elevated pillar heads were evident. Some normal-looking outer hair cells (OHCs) still remained. In C57BL mice, however, early loss of OHCs and extensively damaged stereocilia constituted the primary lesions of the organ of Corti. After exposure to a 2-7 kHz steady noise of 120 dB SPL for 5 min at the age of 1, 2, 3, 6, or 12 (only for CBA) months, compound and permanent threshold shifts (CTS and PTS) at middle frequencies (8-12.5 kHz) reduced with age in CBA mice but remained in C57BL mice. C57BL mice were more severely affected by noise than the age-matched CBA mice. The amount of recovery from CTS to PTS was, however, independent of age and strain. Pathological changes of the organ of Corti were correlated with noise-induced PTS. Possibilities for prediction of susceptible individuals were tested. At 6 months of age, there was only 2% risk of classifying C57BL mice as CBA mice by pre-exposure thresholds at the high frequency (31.5 kHz), but about 40% risk by CTS at the middle frequency (12.5 kHz), or vice versa. With increasing age, the progress of the interaction between noise trauma and aging had two phases for both strains of mice. First an additivity and then, at total threshold shifts of 30-50 dB, a blocking-like interaction were observed. The rate of progression in post-noise hearing loss did not exceed the spontaneous rate of age-related degeneration. The difference between exposed and non-exposed groups decreased with advancing age for both strains of mice.(ABSTRACT TRUNCATED AT 400 WORDS)