# Microglial Activity on Injured Motoneurons

> **NIH NIH F31** · EMORY UNIVERSITY · 2023 · $50,194

## Abstract

Project Summary
Peripheral nerve injuries (PNI) cause motoneuron (MN) axotomy, endangering MNs to cell death which results
in individuals never achieving a full functional recovery. Therefore, identifying the mechanisms which govern
selective MN loss following an injury or insult is crucial for therapeutic advancement in MN disease and for
improving patient outcomes. Research has shown microglia become activated, proliferate and migrate to injured
MN cell bodies after PNI, displaying a range of characteristics from pro-regenerative to degenerative. Currently,
it is unknown what types of microglia-MN interactions occur on injured MNs destined for survival or cell death. It
is also unknown how microglia monitor MN health status, how this relates to MN fate, or what signaling
mechanisms regulate these relationships. Our objective is to identify microglial dynamics and cellular
communication with injured MNs that determine MN fate following PNI. We will first visualize microglia-MN
interactions using advanced microscopy methods and then probe for signaling mechanisms that may regulate
microglia behavior on MNs of various health statuses. Colony Stimulating Factor 1 (CSF1), Triggering Receptor
Expressed on Myeloid Cells 2 (TREM2), and Fc Receptors (FcR) have all been independently shown to modulate
microglial activation via DNAX activating protein of 12kDa (DAP12) and Spleen Tyrosine Kinase (SYK)
activation. Literature has shown CSF1 is necessary for microglia proliferation and migration towards injured MNs.
Preliminary data shows FcRs are expressed on all activated microglia, whereas TREM2 has a greater expression
on microglia surrounding dying MNs compared to surviving or healthy MNs. Given the previous research and
our preliminary findings, I predict that microglia will display different dynamics and uptake of MN content
depending on the MN health status and that the switch between protective to death environments is
governed by the degree of synergistic activation of DAP12 and SYK; more specifically that TREM2 is acting
as a molecular switch. To test this, I will use a PNI mouse model (sciatic axotomy) with microglia genetically
labeled with GFP and axotomized MNs retrogradely labeled from muscle. This will allow the investigation of
microglial-MN interactions on injured MNs of different health statuses. In aim 1, I will quantitatively characterize
microglia-MN dynamics with confocal, two-photon, and super-resolution STED microscopy. This aim will reveal
how microglia could change from sampling MN contents through endocytosis or trogocytosis to MN removal by
neuronal phagocytosis. In aim 2, I will investigate signaling mechanisms that govern microglial phenotypes and
their subsequent effect on MN fate. Specifically, we will develop a TREM2 microglia knock-out mouse model to
analyze resulting microglia phenotypes and MN interactions, signaling cascades, and any effects on MN
regeneration or cell death. This research will provide foundations for neu...

## Key facts

- **NIH application ID:** 10751692
- **Project number:** 1F31NS130993-01A1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** TANA POTTORF
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $50,194
- **Award type:** 1
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10751692

## Citation

> US National Institutes of Health, RePORTER application 10751692, Microglial Activity on Injured Motoneurons (1F31NS130993-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10751692. Licensed CC0.

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