Exposure-duration-associated auditory dysfunction and cochlear presynaptic ribbon alterations during simulated high-altitude hypobaric hypoxia in mice
4 affiliations
- 1Department of Otolaryngology-Head and Neck Surgery, Qinghai University Affiliated Hospital (The Clinical Medical School), Qinghai University
- 2Research Center for High Altitude Medicine, School of Medicine, Qinghai University
- 3Key Laboratory for Application of High-altitude Medicine, Qinghai University
- 4Department of Otolaryngology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
Abstract
Background: High-altitude hypobaric hypoxia can alter auditory function, but the temporal relationships among cochlear dysfunction, hair-cell integrity, inner-hair-cell presynaptic ribbons, and redox-bioenergetic disturbances remain unclear.
Methods: Eighty male C57BL/6J mice were assigned to an ambient-pressure control group in Xining, China (approximately 2,260 m), or to nominal 3-, 15-, or 30-day simulated hypobaric-hypoxia exposure groups ( n = 20 per group). Chamber entry was staggered, and terminal assessments and tissue collection were completed within a period of less than 24 h. Separate animal subsets were used for auditory brainstem response (ABR) recording and hematological assessment. ABR thresholds, wave I latency, and wave I peak-to-trough amplitude were evaluated. Hair-cell survival and CtBP2-positive presynaptic ribbons were assessed by confocal microscopy. Hematological indices, 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine-related immunoreactivity, whole-cochlear ATP content, and JC-1-defined mitochondrial polarization were also assessed.
Results: Red blood cell count, hemoglobin concentration, and hematocrit were increased at all exposure durations. Exposure group was associated with altered ABR thresholds and wave I measures. Control-focused comparisons showed prolonged wave I latency at 4 and 8 kHz in all hypoxia groups, whereas wave I amplitude at 90 dB SPL was lower at both frequencies only after 15 days. OHC survival did not differ significantly among groups, and no overt IHC loss was observed. CtBP2-positive puncta were reduced in the basal turn after 3 days and in all cochlear turns after 15 days. 4-HNE immunoreactivity increased at all time points, whereas 8-OHdG-related immunoreactivity increased after 3 and 15 days. Whole-cochlear ATP content was reduced at all time points. At 30 days, JC-1 analysis indicated a shift toward mitochondrial depolarization in mixed cochlear-cell suspensions.
Conclusion: Simulated high-altitude hypobaric-chamber exposure was associated with an exposure-duration-associated and endpoint-specific cochlear phenotype. Auditory abnormalities and presynaptic ribbon alterations occurred without substantial hair-cell loss and were accompanied by oxidative and bioenergetic disturbances. The pattern of abnormalities varied across exposure groups and endpoints.
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BibTeX
@article{zhang2026exposuredurationassociated,
title = {{Exposure-duration-associated auditory dysfunction and cochlear presynaptic ribbon alterations during simulated high-altitude hypobaric hypoxia in mice}},
author = {Qingping Zhang and Guanghao Yue and Ying Zhang and Shanhong Li and Wenjun Cao and Xiaoli Zhang and Benhong Ren and Chenguang Zhang and Chaohua Wang and Wanru Chen and Tana Wuren and Bin Guo and Yi Wang},
journal = {Frontiers in Neurology},
year = {2026},
month = oct,
doi = {10.3389/fneur.2026.1963563},
url = {https://www.frontiersin.org/articles/10.3389/fneur.2026.1963563/full},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Exposure-duration-associated auditory dysfunction and cochlear presynaptic ribbon alterations during simulated high-altitude hypobaric hypoxia in mice
AU - Qingping Zhang
AU - Guanghao Yue
AU - Ying Zhang
AU - Shanhong Li
AU - Wenjun Cao
AU - Xiaoli Zhang
AU - Benhong Ren
AU - Chenguang Zhang
AU - Chaohua Wang
AU - Wanru Chen
AU - Tana Wuren
AU - Bin Guo
AU - Yi Wang
PY - 2026
DA - 2026/10/15
JO - Frontiers in Neurology
DO - 10.3389/fneur.2026.1963563
UR - https://www.frontiersin.org/articles/10.3389/fneur.2026.1963563/full
AB - Background: High-altitude hypobaric hypoxia can alter auditory function, but the temporal relationships among cochlear dysfunction, hair-cell integrity, inner-hair-cell presynaptic ribbons, and redox-bioenergetic disturbances remain unclear. Methods: Eighty male C57BL/6J mice were assigned to an ambient-pressure control group in Xining, China (approximately 2,260 m), or to nominal 3-, 15-, or 30-day simulated hypobaric-hypoxia exposure groups ( n = 20 per group). Chamber entry was staggered, and terminal assessments and tissue collection were completed within a period of less than 24 h. Separate animal subsets were used for auditory brainstem response (ABR) recording and hematological assessment. ABR thresholds, wave I latency, and wave I peak-to-trough amplitude were evaluated. Hair-cell survival and CtBP2-positive presynaptic ribbons were assessed by confocal microscopy. Hematological indices, 4-hydroxynonenal (4-HNE) and 8-hydroxy-2′-deoxyguanosine-related immunoreactivity, whole-cochlear ATP content, and JC-1-defined mitochondrial polarization were also assessed. Results: Red blood cell count, hemoglobin concentration, and hematocrit were increased at all exposure durations. Exposure group was associated with altered ABR thresholds and wave I measures. Control-focused comparisons showed prolonged wave I latency at 4 and 8 kHz in all hypoxia groups, whereas wave I amplitude at 90 dB SPL was lower at both frequencies only after 15 days. OHC survival did not differ significantly among groups, and no overt IHC loss was observed. CtBP2-positive puncta were reduced in the basal turn after 3 days and in all cochlear turns after 15 days. 4-HNE immunoreactivity increased at all time points, whereas 8-OHdG-related immunoreactivity increased after 3 and 15 days. Whole-cochlear ATP content was reduced at all time points. At 30 days, JC-1 analysis indicated a shift toward mitochondrial depolarization in mixed cochlear-cell suspensions. Conclusion: Simulated high-altitude hypobaric-chamber exposure was associated with an exposure-duration-associated and endpoint-specific cochlear phenotype. Auditory abnormalities and presynaptic ribbon alterations occurred without substantial hair-cell loss and were accompanied by oxidative and bioenergetic disturbances. The pattern of abnormalities varied across exposure groups and endpoints.
SN - 1664-2295
ER -