Abstract
Background: Olfaction is known to be impaired by aging. We hypothesized that insulin-like growth factor-1 (IGF-1) administered at an appropriate dose could prevent age-induced negative effects on olfactory receptor neurons (ORNs). We explored the effects of low- and high-dose administration of IGF-1 on the ORN cell system in aged mice and investigated the involvement of the cellular mechanisms of IGF-1 in the regeneration of ORNs in aged mice.Methods: We subcutaneously administered recombinant human IGF-1 (rhIGF-1) to 16-month-old male mice over 56 days, and then examined the histological effects of rhGF-1 on cellular composition, cell proliferation, and cell death in the aged olfactory epithelium (OE), by comparing among saline-treated and low- and high-dose rhIGF-1-treated mice.Results: Low-dose rhIGF-1 administration increased the numbers of olfactory progenitors, immature ORNs, and mature ORNs in the OE, despite an increase in Cas3+ apoptotic cells. Notably, high-dose rhIGF-1 administration increased the numbers of only immature ORNs, not olfactory progenitors and mature ORNs, with a concurrent increase in apoptotic cells.Conclusion: Our data suggest that in aged mice, IGF-1 administered at an appropriate dose could increase the number of mature ORNs and further human studies may contribute to the development of treatments for aging-related olfactory impairment.
Highlights
Olfaction is known to be impaired by aging
We found that the number of olfactory marker protein (OMP)+ mature olfactory receptor neuron (ORN) was significantly higher in the low-dose recombinant human IGF-1 (rhIGF-1)-treated group compared to the saline-treated and high-dose rhIGF-1-treated groups
The number of growthassociated protein 43 (GAP43)+ immature ORNs significantly increased in both the low- and high-dose rhIGF-1-treated groups compared to the saline-treated group (Figures 2A–C and Supplementary Figure S1)
Summary
Aging negatively affects the ORN cell system in the olfactory neuroepithelium (OE) (Ueha et al, 2018a). IGF-1 and Aged Olfactory Epithelium cytokines, neurotrophins, and growth factors, induce differentiation and maturation of immature ORNs (Buiakova et al, 1996; Nickell et al, 2012; Heron et al, 2013). We hypothesized that insulinlike growth factor-1 (IGF-1) administered at an appropriate dose could prevent ageinduced negative effects on olfactory receptor neurons (ORNs). We explored the effects of low- and high-dose administration of IGF-1 on the ORN cell system in aged mice and investigated the involvement of the cellular mechanisms of IGF-1 in the regeneration of ORNs in aged mice
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