# Role of Nrf2 in oligodendrocyte development and ischemic response

> **NIH NIH F31** · UNIVERSITY OF COLORADO DENVER · 2020 · $32,542

## Abstract

Role of Nrf2 in oligodendrocyte development and ischemic response – Project Summary
White matter injury is a crucial component of ischemic stroke pathophysiology. In addition to local neuronal
death, ischemia damages oligodendrocytes, the myelin-producing cells of the central nervous system. This
causes secondary damage to myelinated axons connecting brain regions, effectively increasing the scope of
neuronal injury. Stroke susceptibility varies with age, and the juvenile period is characterized by greater stroke
recovery than at other ages. Previous work from our lab has shown that in the juvenile brain, oligodendrocytes
and myelinated axons are resistant to ischemic injury. Interestingly, the juvenile period is the peak of central
nervous system myelination, which imposes heavy metabolic demands on oligodendrocytes. One possible
mechanism of juvenile oligodendrocyte ischemic resistance is that active myelination requires increased
antioxidant capacity that confers protection from ischemic injury. However, the mechanisms by which
oligodendrocytes cope with the unique metabolic demands of myelination remain unknown. Analysis of acutely
isolated juvenile and adult oligodendrocytes uncovered differential transcriptional regulation of Nrf2, a
transcription factor best known for driving glutathione synthesis and metabolism in response to oxidative
stress. Nrf2 plays a role in ischemic responses in several cell types in the central nervous system, and it can
protect oligodendrocytes from reactive oxygen species. Moreover, global Nrf2 knockouts develop vacuolar
myelin degeneration as they age. However, the role of Nrf2 in mediating oligodendrocyte development and
response to ischemia remains unknown. The current proposal investigates oligodendrocyte reactive oxygen
species management in developmental and pathological contexts. We will utilize transgenic Cre/lox mouse
technology and in vitro systems to manipulate Nrf2 specifically in the oligodendrocyte lineage and determine its
role during myelination. The Cre/lox system will also be utilized in conjunction with the Herson laboratory
juvenile stroke model to investigate the role of oligodendroglial Nrf2 in juvenile ischemic resistance.
Understanding the mechanisms by which the juvenile brain copes with ischemic injury can inform treatment
options for patients of different ages and provide insight into central nervous system development.

## Key facts

- **NIH application ID:** 9824562
- **Project number:** 5F31NS105395-03
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** Dylan Verden
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,542
- **Award type:** 5
- **Project period:** 2017-12-01 → 2020-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9824562

## Citation

> US National Institutes of Health, RePORTER application 9824562, Role of Nrf2 in oligodendrocyte development and ischemic response (5F31NS105395-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9824562. Licensed CC0.

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