The C57BL/6J mouse has been a useful model of presbycusis, as it displays an accelerated age-related peripheral hearing loss. The medial olivocochlear efferent feedback (MOC) system plays a role in suppressing cochlear outer hair cell (OHC) responses, particularly for background noise. Neurons of the MOC system are located in the superior olivary complex, particularly in the dorsomedial periolivary nucleus (DMPO) and in the ventral nucleus of the trapezoid body (VNTB). We previously discovered that the function of the MOC system declines with age prior to OHC degeneration, as measured by contralateral suppression (CS) of distortion product otoacoustic emissions (DPOAEs) in humans and CBA mice. The present study aimed to determine the time course of age changes in MOC function in C57s. DPOAE amplitudes and CS of DPOAEs were collected for C57s from 6 to 40 weeks of age. MOC responses were observed at 6 weeks but were gone at middle (15-30 kHz) and high (30-45 kHz) frequencies by 8 weeks. Quantitative stereological analyses of Nissl sections revealed smaller neurons in the DMPO and VNTB of young adult C57s compared with CBAs. These findings suggest that reduced neuron size may underlie part of the noteworthy rapid decline of the C57 efferent system. In conclusion, the C57 mouse has MOC function at 6 weeks, but it declines quickly, preceding the progression of peripheral age-related sensitivity deficits and hearing loss in this mouse strain.

We recently discovered that progestin in hormone replacement therapy (HRT) for postmenopausal women has detrimental effects on the ear and central auditory system (Guimaraes et al., Proc. Nat. Acad. Sci. -USA, 103: 14246-9). To start determining the generality and neural bases of these human findings, the present study examined the effects of combination HRT (estrogen+progestin) and estrogen alone on hearing in perimenopausal mice. Specifically, auditory brainstem responses (ABRs-sensitivity of the auditory system) and distortion product otoacoustic emissions (DPOAEscochlear outer hair cell system) were employed. Middle age female CBA mice received either a timerelease, subcutaneous implanted pellet of estrogen+progestin, estrogen alone, or placebo. Longitudinal comparisons of ABR threshold data obtained at 4 months of treatment revealed statistically significant declines in auditory sensitivity over time for the combined estrogen+progestin treatment group, with the estrogen only group revealing milder changes at 3, 6 and 32 kHz. DPOAE testing revealed statistically significant differences for the estrogen+progestin treatment group in the high and middle frequency ranges (15-29 and 30-45kHz) after as early as 2 months of treatment (p<0.01 and p<0.001, respectively). Statistically significant changes were also seen at 4 months of treatment across all frequencies for the combined HRT group. These data suggest that estrogen +progestin HRT therapy of 4 months duration impairs outer hair cell functioning and overall auditory sensitivity. These findings indicate that estrogen+progestin HRT may actually accelerate age-related hearing loss, relative to estrogen monotherapy; findings that are consistent with the clinical hearing loss observed in aging women that have taken combination HRT.

Recently, we characterized the more severe nature of hearing loss in aged Type 2 diabetic human subjects. The current study prospectively assessed hearing abilities in middle age CBA/CaJ mice with Type 1 diabetes mellitus (T1DM) (STZ injection) or Type 2 diabetes mellitus (T2DM) (high fat diet), for a period of 6 months. Blood glucose, body weight and auditory tests (Auditory Brainstem Response-ABR, Distortion Product Otoacoustic Emissions-DPOAE) were evaluated at baseline and every 2 months. Tone and broadband noise-burst responses in the inferior colliculus were obtained at 6 months. Body weights of controls did not change over 6 months (~32g), but there was a significant (~5g) decline in the T1DM, while T2DM exhibited ~10g weight gain. Blood glucose levels significantly increased: 3 fold for T1DM, 1.3 fold for T2DM; with no significant changes in controls. ABR threshold elevations were found for both types of diabetes, but were most pronounced in the T2DM, starting as early as 2 months after induction of diabetes. A decline of mean DPOAE amplitudes was observed in both diabetic groups at high frequencies, and for the T2DM at low frequencies. In contrast to ABR thresholds, tone and noise thresholds in the inferior colliculus were lower for both diabetic groups. Induction of diabetes in middle-aged CBA/CaJ mice promotes amplification of age-related peripheral hearing loss which makes it a suitable model for studying the interaction of age-related hearing loss and diabetes. On the other hand, initial results of effects from very high blood glucose level (T1DM) on the auditory midbrain showed disruption of central inhibition, increased response synchrony or enhanced excitation in the inferior colliculus.