Chronic intranasal corticosteroid treatment induces degeneration of olfactory sensory neurons in normal and allergic rhinitis mice

Abstract

BackgroundNasal eosinophilic inflammation is the therapeutic target for olfactory dysfunction in allergic rhinitis (AR). Intranasal corticosteroids are commonly considered to offer targetable benefit given their immunosuppressive property. However, experimental evidence suggests that continuous corticosteroid exposure may directly cause olfactory damage by disrupting the turnover of olfactory sensory neurons (OSNs). This potentially deleterious effect of corticosteroids calls into question their long‐term topical use for treating olfactory loss related to AR. The aim of this study was to assess the impacts of chronic intranasal corticosteroid treatment on olfactory function and OSN population in mice under normal and pathological conditions.MethodsBALB/c mice were intranasally treated with fluticasone propionate (FP, 0.3 mg/kg) for up to 8 weeks. Additional mice were used to establish an ovalbumin‐induced mouse model of AR, followed by nasal challenge with ovalbumin for 8 weeks in the presence or absence of intranasal FP treatment. The authors examined olfactory function, OSN existence, neuronal turnover, and nasal inflammation using behavioral test, histological analyses, Western blotting, and enzyme‐linked immunosorbent assay.ResultsIntranasal treatment with FP for 8 weeks (FP‐wk8) reduced odor sensitivity in normal mice. This reduction was concomitant with loss of OSNs and the axons projecting to the olfactory bulb, primarily resulting from increased neuronal apoptosis. In FP‐wk8 AR mice, intranasal FP treatment attenuated olfactory impairment and eosinophilic inflammation but failed to reconstitute OSN population and axonal projections.ConclusionThese results suggest that chronic intranasal corticosteroid treatment contributes to OSN degeneration that may reduce the therapeutic effectiveness for AR‐related olfactory loss.

Apoptosis and turnover disruption of olfactory sensory neurons in eosinophilic chronic rhinosinusitis

“…Furthermore, there are unexpected findings that topical corticosteroids may reduce olfactory function by inducing neuronal apoptosis and OSN turnover disturbance ( Takanosawa et al, 2009 ; Crisafulli et al, 2018 ). In an allergic rhinitis mouse model, intranasal fluticasone propionate treatment improves olfactory function and reduces EOS-associated inflammation in OM but fails to rebuild a mature OSN population ( Li et al, 2023 ).…”

“…Slight or moderate OSN loss without detectable OD in patients with CRS can lead to reduced OB volumes ( Rombaux et al, 2008 ). Results from the murine OD model imply that the decline of olfactory function can be detected only when OSN loss reaches a certain level ( Li et al, 2023 ). Changes in OB size are more sensitive than OD in detecting OSN loss in patients with CRS.…”

Olfactory dysfunction and the role of stem cells in the regeneration of olfactory neurons

“…Lamanthia and colleagues have demonstrated that retinoic acid (RA), a member of the steroid/thyroid signaling molecule superfamily, serves as a significant regulatory factor in morphogenesis, differentiation, and regeneration in mammalian olfactory pathways [ 67 ]. However, studies indicate that intranasal corticosteroid treatment for 8 weeks (FP-wk8) can diminish the odor sensitivity of normal mice, suggesting that prolonged intranasal corticosteroid treatment may lead to degeneration of olfactory sensory neurons, thereby affecting treatment efficacy [ 68 ].…”

The olfactory bulb: A neuroendocrine spotlight on feeding and metabolism

“…While considered safe a negative impact on paediatric growth is discussed in the literature 142,143 . Further, chronic intranasal corticosteroid treatment is associated with impaired olfactory function due to neuronal degeneration 144 …”