The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice
Abstract Background Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these re...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-03-01
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| Series: | Biology of Sex Differences |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s13293-018-0171-0 |
| _version_ | 1831790969336365056 |
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| author | Béatrice Milon Sunayana Mitra Yang Song Zachary Margulies Ryan Casserly Virginia Drake Jessica A. Mong Didier A. Depireux Ronna Hertzano |
| author_facet | Béatrice Milon Sunayana Mitra Yang Song Zachary Margulies Ryan Casserly Virginia Drake Jessica A. Mong Didier A. Depireux Ronna Hertzano |
| author_sort | Béatrice Milon |
| collection | DOAJ |
| description | Abstract Background Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice. Methods Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15–21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses. Results We found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p < 0.0001) and PTS at 16, 24, and 32 kHz (16 and 24 kHz p < 0.001, 32 kHz p < 0.01). This sexual dimorphic effect could not be explained by a differential loss of sensory cells or synapses but was reflected in the amplitude and amplitude progression of wave I of the ABR, which correlates with outer hair cell (OHC) function. Finally, the frequency of the protective effect of SAHA differed significantly between males (PTS, 24 kHz, p = 0.002) and females (PTS, 16 kHz, p = 0.003), and the magnitude of the protection was smaller in females than in males. Importantly, the magnitude of the protection by SAHA was smaller than the effect of sex as a biological factor in the vehicle-injected mice. Conclusions These results indicate that female mice are significantly protected from NIHL in comparison to males and that therapeutics for NIHL may have a different effect in males and females. The data highlight the importance of analyzing NIHL experiments from males and females, separately. Finally, these data also raise the possibility of effectors in the estrogen signaling pathway as novel therapeutics for NIHL. |
| first_indexed | 2024-12-22T14:44:05Z |
| format | Article |
| id | doaj.art-d08bd6e2934744c89852790dba801079 |
| institution | Directory Open Access Journal |
| issn | 2042-6410 |
| language | English |
| last_indexed | 2024-12-22T14:44:05Z |
| publishDate | 2018-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Biology of Sex Differences |
| spelling | doaj.art-d08bd6e2934744c89852790dba8010792022-12-21T18:22:30ZengBMCBiology of Sex Differences2042-64102018-03-019111410.1186/s13293-018-0171-0The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in miceBéatrice Milon0Sunayana Mitra1Yang Song2Zachary Margulies3Ryan Casserly4Virginia Drake5Jessica A. Mong6Didier A. Depireux7Ronna Hertzano8Department of Otorhinolaryngology - Head and Neck Surgery, University of MarylandDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandInstitute for Genome Science, University of Maryland School of MedicineDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandDepartment of Pharmacology, University of Maryland School of MedicineDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandDepartment of Otorhinolaryngology - Head and Neck Surgery, University of MarylandAbstract Background Noise-induced hearing loss (NIHL) is the most prevalent form of acquired hearing loss and affects about 40 million US adults. Among the suggested therapeutics tested in rodents, suberoylanilide hydroxamic acid (SAHA) has been shown to be otoprotective from NIHL; however, these results were limited to male mice. Methods Here we tested the effect of SAHA on the hearing of 10-week-old B6CBAF1/J mice of both sexes, which were exposed to 2 h of octave-band noise (101 dB SPL centered at 11.3 kHz). Hearing was assessed by measuring auditory brainstem responses (ABR) at 8, 16, 24, and 32 kHz, 1 week before, as well as at 24 h and 15–21 days following exposure (baseline, compound threshold shift (CTS) and permanent threshold shift (PTS), respectively), followed by histologic analyses. Results We found significant differences in the CTS and PTS of the control (vehicle injected) mice to noise, where females had a significantly smaller CTS at 16 and 24 kHz (p < 0.0001) and PTS at 16, 24, and 32 kHz (16 and 24 kHz p < 0.001, 32 kHz p < 0.01). This sexual dimorphic effect could not be explained by a differential loss of sensory cells or synapses but was reflected in the amplitude and amplitude progression of wave I of the ABR, which correlates with outer hair cell (OHC) function. Finally, the frequency of the protective effect of SAHA differed significantly between males (PTS, 24 kHz, p = 0.002) and females (PTS, 16 kHz, p = 0.003), and the magnitude of the protection was smaller in females than in males. Importantly, the magnitude of the protection by SAHA was smaller than the effect of sex as a biological factor in the vehicle-injected mice. Conclusions These results indicate that female mice are significantly protected from NIHL in comparison to males and that therapeutics for NIHL may have a different effect in males and females. The data highlight the importance of analyzing NIHL experiments from males and females, separately. Finally, these data also raise the possibility of effectors in the estrogen signaling pathway as novel therapeutics for NIHL.http://link.springer.com/article/10.1186/s13293-018-0171-0Noise-induced hearing lossSex differencesSAHAB6CBAF1/J miceInner earABR |
| spellingShingle | Béatrice Milon Sunayana Mitra Yang Song Zachary Margulies Ryan Casserly Virginia Drake Jessica A. Mong Didier A. Depireux Ronna Hertzano The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice Biology of Sex Differences Noise-induced hearing loss Sex differences SAHA B6CBAF1/J mice Inner ear ABR |
| title | The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| title_full | The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| title_fullStr | The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| title_full_unstemmed | The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| title_short | The impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| title_sort | impact of biological sex on the response to noise and otoprotective therapies against acoustic injury in mice |
| topic | Noise-induced hearing loss Sex differences SAHA B6CBAF1/J mice Inner ear ABR |
| url | http://link.springer.com/article/10.1186/s13293-018-0171-0 |
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