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Damage of Inner Ear Sensory Hair Cells via Mitochondrial Loss in a Murine Model of Sleep Apnea With Chronic Intermittent Hypoxia

 Young Joon Seo  ;  Hyun Mi Ju  ;  Sun Hee Lee  ;  Sang Hyun Kwak  ;  Min Jung Kang  ;  Joo-Heon Yoon  ;  Chang-Hoon Kim  ;  Hyung-Ju Cho 
 SLEEP , Vol.40(9) : zsx106, 2017 
Journal Title
Issue Date
Animals ; Disease Models, Animal* ; Hair Cells, Auditory/pathology* ; Hypoxia/complications ; Hypoxia/pathology* ; Hypoxia/physiopathology* ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/pathology* ; Random Allocation ; Sleep Apnea Syndromes/etiology ; Sleep Apnea Syndromes/pathology* ; Sleep Apnea Syndromes/physiopathology* ; Sleep Apnea, Obstructive/complications ; Sleep Apnea, Obstructive/pathology ; Sleep Apnea, Obstructive/physiopathology
chronic intermittent hypoxia ; hearing impairment ; mitochondria ; murine model ; sleep apnea
Study Objectives: Investigating the exact pathophysiology of obstructive sleep apnea syndrome (OSAS)-induced hearing loss is critical. We sought to verify the hypothesis that a correlation exists between mitochondrial dysfunction in inner ear hair cells and the auditory dysfunction induced by chronic intermittent hypoxia (CIH) in a murine model of sleep apnea.

Methods: C57BL/6J adult male mice were randomized to 4 weeks of CIH (n = 12) or normoxia (Sham) (n = 12). Hearing threshold was determined by auditory brainstem response. The activity of mitochondria was compared between CIH and Sham mice. Histological assessment and transmission electron microscopy were performed for assessing morphologic changes in mitochondria. The number of mtDNA copies as well as the levels of PGC1-α, Tfam, and VDAC (voltage-dependent anion channel) were determined in the hair cells of CIH mice.

Results: We observed that hearing ability in CIH mice was impaired and hair-cell mitochondria in CIH mice were fewer compared to that in Sham and also displayed an aberrant morphology. The mRNA levels of PGC-1α and Tfam were higher in the CIH group than in the Sham group. Moreover, the expression of VDAC was increased in the tectorial membrane, the basilar membrane, and especially in the inner hair cells of CIH mice.

Conclusions: This study using CIH mice as a model for OSAS provides evidence of an association between OSAS and auditory function alteration, as well as of mitochondria being part of the pathophysiology of hearing impairment. Further investigation is required to determine whether mitochondria could serve as a valid target for preventive or therapeutic purposes.
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1. College of Medicine (의과대학) > Dept. of Otorhinolaryngology (이비인후과학교실) > 1. Journal Papers
Yonsei Authors
Cho, Hyung Ju(조형주) ORCID logo https://orcid.org/0000-0002-2851-3225
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