Estrogen Receptor-2 Agonists for Protection Against Noise-Induced Hidden Hearing Loss in Female Mice

Authors

• B Alleva
• F Pratto
• D Dahiya
• RD Camerini-Otero

Abstract

One of the most common forms of hearing loss in adults is noise-induced hidden hearing loss (NIHHL). A noise exposure that only causes a temporary threshold shift (TTS) can nevertheless result in permanent damage to ribbon synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs). Work from our laboratory shows that female mice are less susceptible to NIHL, and that this protection is due to endogenous 17β-estradiol. Additionally, this protective effect is partially mediated through estrogen receptor β (ESR2). In this study we investigate whether augmentation of ESR2 signaling via administration of DPN (diarylpropionitrile, an ESR2 specific agonist) or 17β-estradiol (E2) can protect female mice against NIHHL.
Female B6CBAF1/J mice at 8 weeks, were implanted with pellets containing DPN, E2, or a placebo. Baseline auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) thresholds were recorded at 9 weeks of age. At 10 weeks, mice were exposed to noise (8-16 kHz, 93- or 97-dB SPL, for 2-hours). ABRs and DPOAEs were re-evaluated at 1-day, 1-week, and 6-weeks after noise exposure.
Comparison of ABR and DPOAE threshold shifts between treated and placebo animals revealed lower threshold shifts for the E2- and DPN-treated mice. Histologically, treatment with E2 and DPN resulted in significantly higher survival of IHC synapses 6-weeks after noise exposure at 24 kHz frequency.
These results show that augmentation of ESR2-mediated signaling ameliorates NIHHL in intact female mice. This study indicates that ESR2 specific agonists, are promising candidates for future clinical trials for hearing preservation in females.

Scientific Focus Area: Neuroscience

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