# The Intranasal Administration of Semaphorin 3A Inhibitor in a Mouse Model of Olfactory Disorder

## TL;DR

This study tested whether a semaphorin 3A inhibitor could help repair damaged olfactory neurons in mice but found no significant improvement from intranasal administration.

## Contribution

The study evaluates the efficacy of intranasal semaphorin 3A inhibitor administration for olfactory neuron regeneration in mice.

## Key findings

- Intranasal semaphorin 3A inhibitor did not significantly promote olfactory sensory neuron regeneration or axonal outgrowth.
- Saline and semaphorin 3A inhibitor treatments showed similar outcomes in axonal projection and epithelium thickness.
- Subcutaneous administration of the inhibitor in rats was previously shown to promote regeneration, suggesting route differences.

## Abstract

This study investigated the effects of intranasal administration of a semaphorin 3A inhibitor (Sema3A-I) in a mouse model of olfactory disorder, where olfactory sensory neuron (OSN) axons had been severely damaged. We performed axotomy (transection of OSN axons) of the OSNs in mice and administered Sema3A‑I intranasally to seven mice and saline to another seven mice. Following treatment, we assessed the thickness of the olfactory epithelium and the regeneration ratio of OSN axons. Intranasal administration of Sema3A-I did not significantly promote OSN regeneration, axonal outgrowth, or improve axonal projection compared to saline administration. Although Sema3A-I administration showed some promotion of axonal outgrowth, the difference was not statistically significant. Continuous subcutaneous administration of Sema3A-I in rats after axotomy promotes OSN regeneration and axonal outgrowth. Given that intranasal administration is minimally invasive, we believe that it may still be a feasible route when combined with additional treatment strategies. Further investigation into administration methods and therapeutic combinations is warranted.