Prestin Regulation and Function in Residual Outer Hair Cells after Noise-Induced Hearing Loss

Abstract

The outer hair cell (OHC) motor protein prestin is necessary for electromotility, which drives cochlear amplification and produces exquisitely sharp frequency tuning. TectaC1509G transgenic mice have hearing loss, and surprisingly have increased OHC prestin levels. We hypothesized, therefore, that prestin up-regulation may represent a generalized response to compensate for a state of hearing loss. In the present study, we sought to determine the effects of noise-induced hearing loss on prestin expression. After noise exposure, we performed cytocochleograms and observed OHC loss only in the basal region of the cochlea. Next, we patch clamped OHCs from the apical turn (9–12 kHz region), where no OHCs were lost, in noise-exposed and age-matched control mice. The non-linear capacitance was significantly higher in noise-exposed mice, consistent with higher functional prestin levels. We then measured prestin protein and mRNA levels in whole-cochlea specimens. Both Western blot and qPCR studies demonstrated increased prestin expression after noise exposure. Finally, we examined the effect of the prestin increase in vivo following noise damage. Immediately after noise exposure, ABR and DPOAE thresholds were elevated by 30–40 dB. While most of the temporary threshold shifts recovered within 3 days, there were additional improvements over the next month. However, DPOAE magnitudes, basilar membrane vibration, and CAP tuning curve measurements from the 9–12 kHz cochlear region demonstrated no differences between noise-exposed mice and control mice. Taken together, these data indicate that prestin is up-regulated by 32–58% in residual OHCs after noise exposure and that the prestin is functional. These findings are consistent with the notion that prestin increases in an attempt to partially compensate for reduced force production because of missing OHCs. However, in regions where there is no OHC loss, the cochlea is able to compensate for the excess prestin in order to maintain stable auditory thresholds and frequency discrimination.

Noninvasive in vivo imaging reveals differences between tectorial membrane and basilar membrane traveling waves in the mouse cochlea

“…Sound stimuli were synthesized in software, output by a speaker, and carried through a tube to enter the ear canal of the mouse as described (48)(49)(50). The sound waveforms were sent through a DAQ (NI-6363, National Instruments) and triggered by the sweep trigger from the laser to synchronize the sound output with the data collection.…”

Aging after Noise Exposure: Acceleration of Cochlear Synaptopathy in “Recovered” Ears

“…Although OHCs are not lost acutely from the exposures studied here, exaggeration of agerelated DPOAE threshold shifts and OHC losses after synaptopathic noise, particularly at high frequencies, suggest progressive involvement of cochlear amplifier function. It is possible that noise exposure also leads to early onset of sublethal changes in the expression levels of key proteins such as prestin (Xia et al, 2013).…”

A New Hypothesis on the Frequency Discrimination of the Cochlea

“…Deiters' cells are similar in diameter, independent of the cell's position in the organ of Corti and along the cochlear spiral, with similar morphology on the basilar membrane. They are very stiff and lack the capacity for rapid movements, and we do not know the reason why OHCs and Deiters' cells form a unique angled arrangement and interlock with each other [12,13] . If the basilar membrane was of primary importance and peak vibrations of a particular sound frequency were stimulating OHCs of corresponding region, OHCs would not be necessary to show the different features along the basilar membrane.…”

“…This motor protein, prestin, is necessary for cochlear amplification and sharp frequency tuning [18,19] . Xia et al [13] used a noise exposure protocol to cause hair cell loss localized to the basal region of the cochlea, resulting in high-frequency hearing loss. This caused residual OHCs to increase their expression of prestin mRNA and protein.…”

“…This caused residual OHCs to increase their expression of prestin mRNA and protein. To maintain the stability of auditory thresholds and frequency discrimination, the cochlea increases prestin expression in regions where there is no OHC loss [13] . Recently, Lamas et al [20] demonstrated that acoustic input and efferent activity regulate the expression of prestin at transcriptional and post-transcriptional levels.…”