TY - JOUR
T1 - Chronic intermittent hypoxia impacts the olfactory nervous system in an age-dependent manner
T2 - pilot study
AU - Kim, Boo Young
AU - Lee, Sang Haak
AU - Kim, In Kyoung
AU - Park, Ju Yeon
AU - Bae, Jung Ho
N1 - 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 (2021R1I1A1A01044354).
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
PY - 2023/1
Y1 - 2023/1
N2 - 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.
AB - 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.
KW - Age
KW - Hypoxia
KW - Olfaction
KW - Olfactory dysfunction
KW - Olfactory regeneration
KW - Olfactory system
UR - http://www.scopus.com/inward/record.url?scp=85133254328&partnerID=8YFLogxK
U2 - 10.1007/s00405-022-07529-x
DO - 10.1007/s00405-022-07529-x
M3 - Article
C2 - 35780199
AN - SCOPUS:85133254328
SN - 0937-4477
VL - 280
SP - 241
EP - 248
JO - European Archives of Oto-Rhino-Laryngology
JF - European Archives of Oto-Rhino-Laryngology
IS - 1
ER -