# Oligodendrocyte responses to stresses

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2020 · $374,136

## Abstract

Project Summary
 Myelination is essential for normal nervous system development, and the juvenile period is a major
period of myelination. Differentiation of the oligodendrocyte, the myelinating cell of the CNS, is tightly
regulated, and disruption of oligodendrocyte development leads to neurologic problems, such as periventricular
leukomalacia and retardation. How injury during this period impacts myelination is poorly understood, although
ischemic damage in the perinatal period or adults damages oligodendrocytes along with other cells, driving
major tissue damage. We initiated studies to investigate the impact of juvenile ischemia on CNS myelination,
as this period has distinctly different metabolic demands. We found that despite extensive death of striatal
neurons, oligodendrocytes and myelinated axons were remarkably preserved in the juvenile brain, in stark
contrast to the adult which exhibits extensive oligodendrocyte and myelin injury (Ahrendsen et al., Glia
64:1972, 2016). Quite intriguingly, in addition to oligodendrocyte resistance to ischemic injury in the actively
myelinating juvenile brain, a transgenic mouse line that continues active myelination throughout life also has
relatively protected oligodendrocytes.
 In the proposed studies, we will test the hypotheses that actively myelinating oligodendrocytes have
high levels of anti-oxidant pathway molecules that protect them from ischemic damage, and that such
damage increases their expression of insulin-like growth factor (IGF-1), which acts in an autocrine m
manner to additionally protect myelinating oligodendrocytes. We have three related specific aims that test
these hypotheses by investigating 1) the role of the Nrf2 signaling pathway in actively myelinating
oligodendrocytes in response to ischemia; 2) the role of IGF-1 in protection of actively myelinating
oligodendrocytes; and 3) the role of IGF-1 signaling in conjunction with reactive oxygen species in driving
oligodendrocyte progenitor cell differentiation.

## Key facts

- **NIH application ID:** 9842635
- **Project number:** 5R01NS105788-02
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** WENDY B MACKLIN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $374,136
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9842635

## Citation

> US National Institutes of Health, RePORTER application 9842635, Oligodendrocyte responses to stresses (5R01NS105788-02). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9842635. Licensed CC0.

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