# Olfactory ensheathing cells and microglia contributions to axon removal in the olfactory system.

> **NIH NIH R15** · EAST TENNESSEE STATE UNIVERSITY · 2020 · $423,196

## Abstract

Neurogenesis of olfactory sensory neurons is an ongoing process that starts early in
development, continues in adults, and requires that newly generated axons successfully
navigate through the lamina propria, cross the cribriform plate and enter the central nervous
system. At the same time axonal debris from the neurons that die needs to be removed. The
goal of this proposal is by studying the regenerative capacity of the olfactory epithelium to
understand what are the interactions between olfactory sensory neuron axonal debris, olfactory
ensheathing glia, and microglia during regeneration. Despite the interest in the regeneration
process of these neurons for its potential therapeutic use, the most fundamental features of
injury-related axon growth remain unknown. The same can be said about the olfactory
ensheathing glia that allows this axonal outgrowth. An important event to allow the growing of
new axons is the removal of the old ones after the cell body of the olfactory sensory neuron
died. This is done without any signs of infiltration of microglia in the olfactory nerve layer of the
olfactory bulb. We will begin addressing these questions by using a chemical ablation approach
together with our recently developed genetic fate mapping strategy. With this transgenic mouse,
axons can be tracked with extraordinary precision. Injury to the olfactory epithelium will be done
by a single injection of methimazole. Methimazole is a drug commonly used to treat
hyperthyroidism in humans with side effects that include temporal loss of the sense of smell. In
mice, methimazole induces loss of the olfactory epithelium leaving only stem cells that
regenerate the lost neurons. First, we will compare the ability of ensheathing glial cells versus
mononuclear phagocytes to engulf degenerating axons. Because our preliminary data shows no
increase in the infiltration of mononuclear phagocytes, but changes in their morphology were
observed, in the second part of this proposal we will analyze the differentiation of these
phagocytes. Finally, we will look into the signaling molecules that differentiate mononuclear
phagocytes without producing an inflammatory response. The results obtained with this
proposal will prove to be critical in understanding the regeneration process and will be of
general interest to understand how a response to an injury in the central nervous system can
proceed with a minimal inflammatory response.

## Key facts

- **NIH application ID:** 10046940
- **Project number:** 1R15DC018424-01A1
- **Recipient organization:** EAST TENNESSEE STATE UNIVERSITY
- **Principal Investigator:** Diego Javier Rodriguez-Gil
- **Activity code:** R15 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $423,196
- **Award type:** 1
- **Project period:** 2020-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10046940

## Citation

> US National Institutes of Health, RePORTER application 10046940, Olfactory ensheathing cells and microglia contributions to axon removal in the olfactory system. (1R15DC018424-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10046940. Licensed CC0.

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