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Updated: Jul 10, 2026

Modified Experimental Conditions for Noise-Induced Hearing Loss in Mice and Assessment of Hearing Function and Outer Hair Cell Damage
Published on: February 10, 2023
Bcl-2 genes regulate noise-induced hearing loss
Daisuke Yamashita1, Shujiro B Minami, Sho Kanzaki
1Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
Abstract:
Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death.
Insights
The Bcl-2 family proteins, Bcl-xL and Bak, play key roles in preventing or causing sensory cell death after noise exposure. Bcl-xL protects cells from temporary hearing loss, while Bak triggers cell death during permanent hearing loss.
Area of Science:
- Oto-neuroscience
- Molecular biology
- Cellular biology
Background:
- Proteins of the Bcl-2 family regulate apoptosis, a process involved in neuronal cell death.
- Noise-induced hearing loss is a significant health concern linked to neuronal cell death pathways.
- The roles of specific Bcl-2 family proteins in noise-induced hearing loss are not fully understood.
Purpose of the Study:
- To investigate the expression of anti-apoptotic Bcl-xL and pro-apoptotic Bak following noise exposures causing temporary threshold shift (TTS) and permanent threshold shift (PTS).
- To determine the involvement of Bcl-xL and Bak in sensory cell survival or death after intense noise exposure.
Main Methods:
- Animals were exposed to either 100 dB SPL, 4 kHz OBN for 1 hr (TTS) or 120 dB SPL, 4 kHz OBN for 5 hr (PTS).
- Auditory brainstem responses (ABRs) were measured at 4, 8, and 16 kHz before and after noise exposure.
- Immunohistochemical analysis was performed to assess Bcl-xL and Bak expression in cochlear tissues.
Main Results:
- Both TTS and PTS noise exposures increased ABR thresholds.
- ABR thresholds fully recovered after TTS exposure.
- PTS exposure resulted in significant permanent threshold shifts and outer hair cell loss.
- Bcl-xL was highly expressed in outer hair cells after TTS exposure.
- Bak expression was observed following PTS exposure, correlating with cell death.
Conclusions:
- Bcl-2 family proteins are crucial in modulating sensory cell fate following intense noise.
- Bcl-xL is essential for preventing sensory cell death after TTS-inducing noise levels.
- PTS-inducing noise exposure activates Bak, leading to sensory cell death.
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