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Research (R)

PP1312 - The Relationship Between Noise-Induced TTS and Cochlear Synaptopathy in Chinchillas

POSTERS
Location: Halls A1-A2
Instructional Level: Fundamental

    Poster Presenter(s)

  • Alison Lacey

    Doctor of Audiology Student
    University of Texas at Dallas
    Dallas, Texas

    Disclosure(s): No financial or nonfinancial relationships to disclose.

    PDF Handouts Slides

    • Contributor (Not Presenting)(s)

  • AZ

    Andie Zang

    Disclosure(s): No financial or nonfinancial relationships to disclose.

  • Edward Lobarinas, PhD

    Professor
    The University of Texas at Dallas
    PLANO, Texas

    Disclosure(s): No financial or nonfinancial relationships to disclose.

Abstract: Over the last decade animal studies have shown that noise-exposures that produce robust temporary threshold shifts (TTS) but no permanent shifts produce long-term damage to inner hair cell (IHC) presynaptic terminals. This pattern of damage has been called “synaptopathy”. In the present study, we used acute 24h, 89 dB SPL noise exposures that produced 10-35 dB TTS in chinchillas. TTS was assessed using auditory brainstem responses (ABR) at 1-12 kHz. Post-exposure, histology showed evidence of synaptopathy across all animals including those with the smallest TTS. The results suggest that robust TTS is not necessary for producing synaptopathy.

Summary:

High level noise exposures from the workplace or recreational activities are a major hearing healthcare problem that affects millions of people worldwide. Exposure to intense levels of sound often produces temporary shifts in hearing sensitivity that can become permanent.  These permanent threshold shifts (PTS) are associated with irreversible damage to the sensitive sensory structures within the cochlea including outer hair cells (OHCs), inner hair cells (IHC) and their stereocilia which leads to sensorineural hearing loss (SNHL). It was previously assumed that in cases of TTS without PTS, cochlear sensory cells did not sustain permanent damage. However, several animal studies have shown that noise exposures resulting in TTS can lead to primary neural degeneration of presynaptic elements on IHCs even in the absence of loss of IHCs or OHCs (Kujawa & Liberman, 2009). This irreversible synaptic damage in the absence of hair cell damage is called synaptopathy, previously referred to as “hidden hearing loss.”

This study examines the relationship between noise-induced TTS and synaptic loss in a chinchilla animal model using auditory brainstem response (ABR), distortion product otoacoustic emissions (DPOAE), and histology analysis. Animals were exposed to 89 dB SPL centered around 4 kHz over 24 hours to induce synaptopathic damage. Noise was presented via a Fostex speaker fixed to the front of the noise exposure cage. Speakers were calibrated at multiple points throughout the noise exposure sound field using a sound level meter.

DPOAE measures were used to evaluate the integrity and function of OHCs pre- and post-noise exposure. IHS Smart DPOAE was used to record responses from 1-10 kHz.

ABR thresholds were measured at baseline, 24 hours post-, and 4 weeks post-exposure. The amount of TTS was determined by assessing the shift from baseline at 24 hours post-exposure. ABR testing was performed in a double-walled soundproof booth while the animals were under anesthesia. Ketamine (40 mg/kg) and xylazine (2 mg/kg) were administered via subcutaneous injection by body weight. IHS Smart EP software was used to record ABR responses. Tone burst stimuli were presented at 1-12 kHz and stimulus intensities decreased by 10 dB steps and increased by 5 dB steps until the threshold was obtained. ABR wave-1 amplitudes were recorded at suprathreshold intensities of 90, 80, and 70 dB SPL to evaluate potential reductions, a known marker of synaptopathy.

Following the conclusion of testing, the noise-exposed animals were sacrificed and their cochleas were extracted. Frequency sectioning and imaging of the cochleas was used to determine the extent of synaptic loss in different frequency regions (1, 2, 4, 8, and 12 kHz). 

Following the noise exposure animals incurred a 10-35 dB TTS. Histological analysis revealed a statistically significant reduction in IHC synapse counts with no loss of OHCs. Cochlear histology confirmed that synaptopathy was present in all animals with TTS including those with 10 dB TTS, suggesting that robust TTS is not necessary for producing synaptopathy.

Learning Objectives:

  • Upon completion of this session, the participant will be able to define cochlear synaptopathy (CS) and identify the relationship between noise exposure, TTS and CS.