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Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner: pilot study

  • Rhinology
  • Published:
European Archives of Oto-Rhino-Laryngology Aims and scope Submit manuscript

Abstract

Purpose

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse during sleep, which induces chronic intermittent hypoxia (CIH). CIH results in low-grade inflammation, sympathetic overactivity, and oxidative stress. Nevertheless, it remains unclear how exposure to CIH affects olfaction. The purpose of this study was, therefore, to investigate the cytotoxic effects of CIH exposure on mouse olfactory epithelium and the underlying pathophysiology involved.

Methods

Mice were randomly divided into four groups: Youth mouse (You) + room air (RA), You + intermittent hypoxia (IH), Elderly mouse (Eld) + RA, and Eld + IH (n = 6 mice/group). Mice in the two hypoxia groups were exposed to CIH. The control condition involved exposure to room air (RA) for 4 weeks. Olfactory neuroepithelium was harvested for histologic examination, gene ontology analysis, quantitative real-time polymerase chain reaction (qRT-PCR), and western blotting.

Results

Based on qRT-PCR analysis, olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL mRNA levels were lower, whereas NGFR, CNPase, NGFRAP1, NeuN, and MAP-2 mRNA levels were higher in the You + IH group than in the You + RA group. Olfactory receptor-regulated genes, neurogenesis-related genes and immunohistochemical results were altered in nasal neuroepithelium under CIH exposure.

Conclusions

Based on genetic and cytologic analysis, CIH impacted the olfactory neuroepithelium in an age-dependent manner. Our findings suggest that CIH-induced damage to the olfactory neuroepithelium may induce more severe change in the youth than in the elderly.

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Funding

This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2021R1I1A1A01044354).

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Authors and Affiliations

  1. Department of Otolaryngology-Head and Neck Surgery, School of Medicine, Seoul Hospital, Ewha Womans University, Gangseo-gu, Gonghang-daero 260, Seoul, Korea

    Boo-Young Kim & Jung Ho Bae

  2. Department of Clinical Laboratory, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Eunpyeong, Seoul, Korea

    Sang Haak Lee & In Kyoung Kim

  3. Department of Clinical Laboratory, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Banpo, Seoul, Korea

    Ju Yeon Park

Authors
  1. Boo-Young Kim
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  2. Sang Haak Lee
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  5. Jung Ho Bae
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Contributions

Conceived and designed the manuscript: BYK. Analyzed the data: BYK, JHB, and JYP. Contributed reagents/materials/analysis tools: BYK, IKK, and SHL. Wrote the paper: BYK, IKK, and SHL.

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Correspondence to Boo-Young Kim.

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Kim, BY., Lee, S.H., Kim, I.K. et al. Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner: pilot study. Eur Arch Otorhinolaryngol 280, 241–248 (2023). https://doi.org/10.1007/s00405-022-07529-x

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  • DOI: https://doi.org/10.1007/s00405-022-07529-x

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