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

Abstract

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

Methods: This study established a total of six animal model groups (n=5 per group): control; ovalbumin (OVA)-induced AR; OVA/polyinosinic-polycytidylic acid (poly[I:C])-induced neutrophil-dominant rhinitis; OVA/Staphylococcus enterotoxin B-induced CRS; and two anosmia models induced by chronic intranasal administration of ZnSO4 and intraperitoneal injection of 3-methylindole (3-MI). Olfactory function was evaluated using an open-field food-finding test and a T-maze test one week after model induction. Behavioral test results were analyzed with video analysis software (EthoVision XT). Immunofluorescent staining was conducted to assess histological changes in olfactory sensory neurons (OSNs) and olfactory basal cells.

Results: In the T-maze test, the OVA and OVA/poly(I:C)-induced rhinitis groups showed increased food-finding time compared with the control and CRS groups. The two anosmia mouse models demonstrated statistically significant differences from all other groups. Food-finding time showed significant positive correlations with two novel variables evaluated in this study: total distance moved and average velocity, in both the open-field and T-maze tests. Histologically, the CRS and two anosmia models exhibited a significant decrease in mature and immature OSNs. Additionally, the two rhinitis groups and the CRS group displayed significant changes in the number of immature OSNs. Changes in the basal cell marker cytokeratin-5 were observed specifically 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 drug-induced anosmia, as assessed by histological analysis and behavioral tests. These findings can serve as a reference for future studies on olfaction using mouse models.