Differences in Mechanisms of Steroid Therapy and Olfactory Training for Olfactory Loss in Mice

Objective Steroid therapy and olfactory training are common treatments for olfactory loss. Systemic steroid treatment is the most effective approach for treating sinonasal olfactory loss. Olfactory training is typically effective for treating sensorineural olfactory loss. However, the differences in mechanisms of steroid therapy and olfactory training for olfactory dysfunction are unclear. The aim of this study was thus to evaluate the differences in mechanisms of olfactory training and steroid therapy. Subjects and Methods Mice in each group were administered 3-methylindole at a dose of 300 mg/kg. Olfactory function was evaluated with a food-finding test once a week. The olfactory neuroepithelium was harvested for histologic examination and protein analysis. Subsequently, data analysis, gene ontology and pathway analysis, quantitative real-time polymerase chain reaction of mRNA, and western blot analysis were conducted. Results Mice were divided into four groups according to treatment. Control, anosmia, training, and steroid groups resumed food-finding. MMP27, CCL22 and IL18rap mRNA expression were significantly increased in the training group compared to that in the steroid group. IL1R2 mRNA expression was significantly higher in the olfactory neuroepithelium of steroid-treated mice than in that of the training group mice. Conclusions Steroid therapy improved olfactory function via anti-inflammatory effects, unlike olfactory training which involved cell regeneration and tissue remodeling. Protein and gene analyses revealed that steroid therapy and olfactory training are underpinned by distinct mechanisms. Selection of the most appropriate treatment will be dependent on the cause of olfactory loss.