The Effects of the Levels of Hypoxia in the Olfactory Nervous System in Mouse Model

Purpose: Intermittent hypoxia (IH) results in low-grade inflammation, sympathetic overactivity, and oxidative stress. However, the specific effects of IH on olfaction have not yet been directly assessed and remain unclear. Therefore, the purpose of this study was to investigate the cytotoxic effects of IH exposure on the mouse olfactory epithelium and the relationship between the concentration of hypoxia and the degree of destruction of the olfactory system. Methods: Thirty mice were randomly divided into six groups: control (room air for 4 weeks), recovery control (room air for 5 weeks), IH 5% oxygen concentration, IH 7% oxygen concentration, recovery 5% hypoxia, and recovery 7% hypoxia groups. Mice in the two hypoxia groups were exposed to 5% and 7% oxygen for 4 weeks. Mice in the two recovery groups were exposed to room air for 1 week after 4 weeks of hypoxia period. Results: Based on, the olfactory marker protein (OMP), Olfr1507, ADCY3, and GNAL were lower, whereas S100b and NGFRAP1 messenger RNA (mRNA) levels were higher in the 5% hypoxia group than those in the control group in the olfactory neuroepithelium. In the brain tissue, the changes in RNA analysis for Olfr 1507, OMP, ADCY, and GNAL mRNA were not typical. However, NeuN and GFAP levels were decreased under 5% hypoxia in the brain tissue. In the recovery state, CNPase, S100b and NeuN levels were increased significantly in both the olfactory neuroepithelium and brain tissue in the 5% hypoxia group. The change in RNA activity in PCR was much higher in the 5% hypoxia group than in the 7% hypoxia group. Conclusions: Our findings suggest that IH damages the olfactory neuroepithelium and brain tissue in mouse model. The activity of olfactory marker genes and neurogenesis in the olfactory neuroepithelium were decreased. The levels of oxygen may be affect changes in the olfactory neuroepithelium. The olfactory ensheathing cell may be a major factor in the recovery of the olfactory neuroepithelium.