Functional and Morphological Changes in the Olfactory Epithelium of Mouse Models with Upper Respiratory Inflammation and Olfactory Dysfunction.

Objectives: This study evaluated behavioral tests and histological findings of allergic rhinitis (AR), chronic rhinosinusitis (CRS), and drug-induced anosmia murine models, comparing the results among groups.

Methods: This study established total six animal model groups: control, ovalbumin (OVA) induced AR, OVA/poly(I:C) induced neutrophilic dominant rhinitis, OVA/staphylococcus enterotoxin B induced CRS, two anosmia models induced by 3-methylindole (3-MI) intraperitoneal injection and chronic ZnSO4 intranasal administration (n=5 in each group). Olfactory function was evaluated using an open-field food-finding test and a T-maze test one week after establishing the models. The results of the behavioral tests were analyzed using video analysis software (EthoVision XT), and the immunofluorescent staining was performed to evaluate the histologic changes of olfactory sensory neurons (OSNs) and olfactory basal cells.

Results: OVA and OVA/poly(I:C) induced rhinitis groups showed increased food finding time compared with control and CRS groups in T-maze test. The two anosmia mouse models showed statistically significant differences from the other groups. There was a significant positive correlation between food-finding time and the two novel variables evaluated in this study: total distance moved and average velocity in both the open-field and T-maze tests. Histologically, there was a significant decrease in the number of mature and immature OSNs in the CRS and two anosmia models. Two rhinitis groups and CRS group showed significant changes in the number of immature OSNs. Additionally, there were changes in the basal cell marker (cytokeratin-5) in the 3-MI model.

Conclusion: This study demonstrated significant differences in olfactory function and histological changes among various mouse models of upper airway inflammation and druginduced anosmia using histological analysis and behavioral test and can be used as a reference for future study on olfaction using mouse models.