Dataset Information

Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure.

ABSTRACT: Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo3, outer hair cells are lost throughout the middle and higher frequencies. SEM reveals persistent damage to some surviving outer hair cell stereocilia. However, DPOAE analysis reveals that some function is preserved in low frequency outer hair cells, despite concomitant profound hearing loss. Inner hair cells, auditory synapses and spiral ganglion neurons are all present after noise exposure in the Foxo3KO/KO fourteen days post noise (DPN). We also report anti-Foxo3 immunofluorescence in adult human outer hair cells. Taken together, these data implicate Foxo3 and its transcriptional targets in outer hair cell survival after noise damage. An additional role for Foxo3 in preserving hearing is likely, as low frequency auditory function is absent in noise exposed Foxo3KO/KOs even though all cells and structures are present.

SUBMITTER: Gilels F

PROVIDER: S-EPMC5430619 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature

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Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure.

Gilels Felicia F Paquette Stephen T ST Beaulac Holly J HJ Bullen Anwen A White Patricia M PM

Scientific reports 20170421 1

Noise induced hearing loss (NIHL) is a disease that affects millions of Americans. Identifying genetic pathways that influence recovery from noise exposure is an important step forward in understanding NIHL. The transcription factor Foxo3 integrates the cellular response to oxidative stress and plays a role in extending lifespan in many organisms, including humans. Here we show that Foxo3 is required for auditory function after noise exposure in a mouse model system, measured by ABR. Absent Foxo ...[more]

PMID: 28432353

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Project description:ObjectivesThe purpose of the present study was to investigate the laboratory efficacy and real-world effectiveness of advanced directional microphones (DM) and digital noise reduction (NR) algorithms (i.e., premium DM/NR features) relative to basic-level DM/NR features of contemporary hearing aids (HAs). The study also examined the effect of premium HAs relative to basic HAs and the effect of DM/NR features relative to no features.DesignFifty-four older adults with mild-to-moderate hearing loss completed a single-blinded crossover trial. Two HA models, one a less-expensive, basic-level device (basic HA) and the other a more-expensive, advanced-level device (premium HA), were used. The DM/NR features of the basic HAs (i.e., basic features) were adaptive DMs and gain-reduction NR with fewer channels. In contrast, the DM/NR features of the premium HAs (i.e., premium features) included adaptive DMs and gain-reduction NR with more channels, bilateral beamformers, speech-seeking DMs, pinna-simulation directivity, reverberation reduction, impulse NR, wind NR, and spatial NR. The trial consisted of four conditions, which were factorial combinations of HA model (premium versus basic) and DM/NR feature status (on versus off). To blind participants regarding the HA technology, no technology details were disclosed and minimal training on how to use the features was provided. In each condition, participants wore bilateral HAs for 5 weeks. Outcomes regarding speech understanding, listening effort, sound quality, localization, and HA satisfaction were measured using laboratory tests, retrospective self-reports (i.e., standardized questionnaires), and in-situ self-reports (i.e., self-reports completed in the real world in real time). A smartphone-based ecological momentary assessment system was used to collect in-situ self-reports.ResultsLaboratory efficacy data generally supported the benefit of premium DM/NR features relative to basic DM/NR, premium HAs relative to basic HAs, and DM/NR features relative to no DM/NR in improving speech understanding and localization performance. Laboratory data also indicated that DM/NR features could improve listening effort and sound quality compared with no features for both basic- and premium-level HAs. For real-world effectiveness, in-situ self-reports first indicated that noisy or very noisy situations did not occur very often in participants' daily lives (10.9% of the time). Although both retrospective and in-situ self-reports indicated that participants were more satisfied with HAs equipped with DM/NR features than without, there was no strong evidence to support the benefit of premium DM/NR features and premium HAs over basic DM/NR features and basic HAs, respectively.ConclusionsAlthough premium DM/NR features and premium HAs outperformed their basic-level counterparts in well-controlled laboratory test conditions, the benefits were not observed in the real world. In contrast, the effect of DM/NR features relative to no features was robust both in the laboratory and in the real world. Therefore, the present study suggests that although both premium and basic DM/NR technologies evaluated in the study have the potential to improve HA outcomes, older adults with mild-to-moderate hearing loss are unlikely to perceive the additional benefits provided by the premium DM/NR features in their daily lives. Limitations concerning the study's generalizability (e.g., participant's lifestyle) are discussed.

Dataset Information

Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure.

Publications

Severe hearing loss and outer hair cell death in homozygous Foxo3 knockout mice after moderate noise exposure.

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