# Age-induced disruptions in remyelination after spinal cord injury

> **NIH NIH F31** · OHIO STATE UNIVERSITY · 2020 · $34,043

## Abstract

PROJECT SUMMARY/ABSTRACT
Spinal cord injury (SCI) is a devastating trauma that affects over 17,000 individuals in the United States per
year, resulting in permanent paralysis for which there are no clinical therapies. These functional deficits are
largely attributed to axon degeneration and extensive demyelination. Since surviving oligodendrocytes (OLs)
cannot self-renew to remyelinate axons, the primary source of new myelin originates from proliferating NG2
progenitor cells. After SCI, it well-characterized that NG2 cells migrate and differentiate into new myelinating
OLs along demyelinated axons. However, preliminary and published data suggest that NG2 cell differentiation
and myelin biogenesis slow with advancing age. The frequency of SCI in the aging population is markedly
increasing, yet the mechanism behind this impaired remyelination remains unknown. Here, we will use loss-of-
function and gain-of-function experiments to investigate signaling pathways that contribute to the age-
dependent decline in NG2 cell function, remyelination, and functional recovery after SCI. In particular, we will
study two signals that regulate oligodendrogenesis: the mammalian target of rapamycin (mTOR) and
glutamate. In Aim 1 we will genetically inhibit mTOR in aged mice to determine if mTOR downregulation
reverses age-related impairments in CNS repair. Single cell RNA sequencing from young and aged mice will
be run to further characterize changes in OL function and mTOR signaling. Then, in Aim 2 we will use viral
vectors to test if overexpressing glutamate is sufficient to promote neuron-glia crosstalk and remyelination in
aged-SCI mice. Collectively, these experiments aim to provide novel insight into how NG2 cells and
myelination are regulated in the aging injured environment. If successful, data from this proposal will be one of
the first to show that specific signaling molecules are responsible for anatomical and functional improvements
in aged-SCI mice. This knowledge will aid in identifying new targets for therapeutic intervention to improve the
quality of life of elderly SCI patients.

## Key facts

- **NIH application ID:** 9989263
- **Project number:** 1F31NS115523-01A1
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** Nicole Pukos
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $34,043
- **Award type:** 1
- **Project period:** 2020-06-01 → 2022-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9989263

## Citation

> US National Institutes of Health, RePORTER application 9989263, Age-induced disruptions in remyelination after spinal cord injury (1F31NS115523-01A1). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9989263. Licensed CC0.

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