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

Abstract

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.

Efficacy and safety of oral corticosteroids and olfactory training in the management of COVID-19-related loss of smell

“…Similarly, the mechanism by which OT and steroid therapy could reduce the risk of PVOD and improve olfaction is yet to be determined. Studies on dysosmic mice suggest that the decision to treat with steroids or OT may ultimately depend on the cause of the olfactory loss [17]. Recently, MRI studies showed signs of inflammation of the olfactory clefts of COVID-19 patients with acute anosmia compared to healthy controls, suggesting a possible role for antiinflammatory drugs such as steroids [18,19].…”

Effects of Urban Particulate Matter on the Olfactory System in a Mouse Model

“…In our previous studies, we reported that OECs could play a role in the recovery of the olfactory epithelium after its destruction. 22,23 OECs have been studied in Western blotting analysis was performed to compare OMP, Olfr1507, ADCY3, GNAL, NGFRAP1, S100, and TACR3 protein expression in the 400UPM group compared with that in the control group. These results show that 400UPM negatively affected OMP, Olfr1507, ADCY3, and GNAL expression in our mouse model.…”

“…The limitation of our study was that this UPM model was not ideal for comparisons with humans, because mice have a stronger regenerative ability than humans, and their olfactory epithelium recovers within 2 to 3 weeks of chemical injury. 10,22,23 And we used fluid mixture using UPM and saline because of ethical issues. Our institution did not permit the use of UPM power model because of concerns regarding the harmfulness to the experimenter's health.…”

Restoration of olfactory dysfunctions by nanomaterials and stem cells-based therapies: Current status and future perspectives

“…Eighty-three percent of the patients had improved smell after systemic treatment, with no difference observed in the topical versus placebo groups. 32 Although the administration of steroids was proven to be effective in many animal models, 33 , 34 studies in humans showed variable outcomes and often had limited efficacy. 35 , 36 In patients with post-traumatic olfactory dysfunction, the treatment effect of steroids was known to occur only in 12%–16% of the patients.…”