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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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 (voltagedependent 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.

Original languageEnglish
Article numberzsx106
JournalSleep
Volume40
Issue number9
DOIs
Publication statusPublished - 2017

Bibliographical note

Funding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (NRF-2015R1C1A1A02036354 to YJS and 2015R1D1A1A02062156 to H-JC). This study was supported in part by a Faculty Research Grant of Yonsei University College of Medicine of 2016 (6-2016-0061) to H-JC and Yonsei University Future-leading Research Initiative of 2016 (2016-22-0115) to C-HK.

All Science Journal Classification (ASJC) codes

  • Clinical Neurology
  • Physiology (medical)

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