Olfactory Ensheathing Cells Mediate Neuroplastic Mechanisms After Olfactory Training in Mouse Model

Background: Several studies have reported beneficial effects of olfactory training (OT) on the olfactory nervous system. However, the mechanisms underlying the regeneration of the olfactory system induced by OT are still under investigation. Objectives: To determine the key mechanisms involved in the olfactory system recovery and to assess the neuroplastic effects of OT. Methods: Thirty healthy female C57BL/6 mice were randomly allocated to 4 groups: control, n = 6; anosmia (no treatment), n = 8; OT, n = 8; and steroid treatment; n = 8. Except for the control group, mice were administered 3-methylindole. Anosmia was assessed using a food-finding test (FFT). The olfactory neuroepithelium was for histological examinations, gene ontology with pathway analyses, RNA, and protein studies. Results: FFT was significantly reduced at 3 weeks in the OT mice versus steroids (78.27 s vs 156.83 s, P <.008) and controls (78.27 s vs 13.14 s, P <.003), although final outcome in the FFT was similar in these groups. Expression of olfactory and neurogenesis marker was higher in the olfactory neuroepithelium of the OT group than in the anosmia group without treatment. The mechanisms underlying olfactory regeneration might be related to early olfactory receptor stimulation, followed by neurotrophic factor stimulation of neuronal plasticity. Conclusion: OT can improve olfactory function and accelerate olfactory recovery. The mechanisms underlying olfactory regeneration might be related to an initial stimulation of olfactory receptors followed by neurogenesis. Olfactory ensheathing cells might play an important role in olfactory regeneration following OT, based on the observed changes in messenger ribonucleic acid (mRNA) and protein expression, as well as the findings of the gene analysis.