The neuroplastic effect of olfactory training to the recovery of olfactory system in mouse model

Abstract

Background Several studies have reported the benefits of olfactory training (OT) in the olfactory nervous system of mouse models. Therefore, in this study we performed next‐generation sequencing to evaluate the effects of OT on mRNA sequencing in the olfactory area. Methods Mice in each group were administered 300 mg of 3‐methylindole per kilogram of mouse weight. The olfactory function was evaluated by 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 4 groups according to treatment. Control, anosmia, training, and steroid group mice resumed food finding. Olfactory Maker Protein, olfr1507, ADCY3, and GNAL mRNA expression was higher in the olfactory neuroepithelium of OT than anosmia group mice. In total, 26,364 mRNAs were analyzed. Comparison of the results of OT vs anosmia revealed that ADCY8,10, GFAP, NGF, NGFR, GFAP, and BDNF mRNAs were upregulated in the gene ontology. Conclusion OT improved olfactory function, as indicated by the food‐finding test. OT improved the olfactory recovery time to stimulate olfactory nerve regeneration. OT may initially stimulate the olfactory receptor, followed by neurogenesis. Steroid therapy and OT operated under completely different mechanisms in the upregulated gene study. These results indicate that OT may be one of the future modalities for treating olfactory impairment.

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

“…21 The four odors were selected due to their proven training effects based on previous human and animal studies. 12,17 Each mouse was placed into a covered plastic case (width  length  height: 200  260  130 mm) containing one of the four odorants. Each mouse was exposed to each odorant for 1 minute with a rest period of 2 minutes between stimuli to prevent olfactory fatigue.…”

“…13 The olfactory system exhibits neuroplasticity via mechanisms that have been extensively investigated at the cognitive and cellular levels. [14][15][16][17] Elucidating the different mechanisms underpinning steroid treatment and OT in olfactory loss will facilitate the application of treatments for olfactory disturbances with various clinical causes. The purpose of this study was to evaluate the different mechanisms of steroid therapy and olfactory training using experimental approaches.…”

Evidence‐based medicine in an evolving field

“…Treatment outcomes were evaluated by both behavioral testing and RNA expression. The study demonstrated more rapid recovery of olfactory function in the olfactory training group, as well as upregulation of the genes associated with neurogenesis, providing additional support for the practice of olfactory training …”

Olfactory training: what is the evidence?

“…Notwithstanding what could be interpreted as marginal mechanistic evidence in human studies, the efficacy of olfactory training is supported by a small number of animal experiments. Kim et al 13 . evaluated olfactory recovery in olfactory‐lesioned mice via a food‐finding test and simulated olfactory training using common odorants over a period of 3 weeks 13 .…”

“…Kim et al 13 . evaluated olfactory recovery in olfactory‐lesioned mice via a food‐finding test and simulated olfactory training using common odorants over a period of 3 weeks 13 . Olfactory training improved olfactory recovery time and was accompanied by changes in gene transcriptional pathways associated with neurogenesis.…”