# Upper-respiratory infection, oligodendrocyte plasticity and behavior

> **NIH NIH R21** · UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN · 2021 · $405,672

## Abstract

SUMMARY
Systemic inflammation causes characteristic changes to behaviors including cognitive impairment, anxiety,
lethargy, fatigue and depression; collectively these behaviors are termed sickness behaviors. While the exact
mechanisms whereby neuroimmune interactions facilitate changes to behavior have not been entirely elucidated,
activation of microglia, the resident immune cells of the brain, are thought to play a role. Intriguingly, microglial
reactivity is a prominent feature of most white matter diseases. White matter abnormalities are a feature of mental
health disorders, including schizophrenia. Furthermore, patients with diseases characterized by hypomyelination
or demyelination exhibit symptoms of sickness behaviors including motor, cognitive, attentional and behavioral
deficits and depression. In the central nervous system (CNS) oligodendrocytes (OLs) are responsible for myelin
formation. Recently, the idea that myelin remains static during adulthood has been challenged and that changes
to myelin can be positively affected by learning a new task or adversely affected by stress. The purpose of this
proposal is to establish a link between infection and inflammation-induced myelin plasticity and sickness behavior
(i.e. behavioral changes resulting from sickness). We have found that influenza infection affects OL-specific gene
transcription and likely affects myelin plasticity. Since experimental influenza infection also causes microglia
reactivity and cognitive impairment we are proposing to test the novel hypothesis that systemic inflammation
stimulates microglia to produce factors that affect myelin plasticity and that these effects underlie changes to
behavior. Since both myelin thickness and length affect neuronal conduction velocity it is easy to envision how
alterations to myelin structure might affect neurocircuitry, modulate synaptic plasticity and influence behavior. In
the first aim we will determine if microglia depletion affects myelin plasticity resulting from influenza infection. In
the second aim we will determine if enhancing myelination inhibits infection-induced sickness behaviors. Through
these experiments we expect to uncover a novel mechanism whereby infections occurring outside the CNS can
modulate brain plasticity and behavior.

## Key facts

- **NIH application ID:** 10373328
- **Project number:** 1R21NS121741-01A1
- **Recipient organization:** UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
- **Principal Investigator:** Andrew Jonathan Steelman
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $405,672
- **Award type:** 1
- **Project period:** 2021-09-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373328

## Citation

> US National Institutes of Health, RePORTER application 10373328, Upper-respiratory infection, oligodendrocyte plasticity and behavior (1R21NS121741-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10373328. Licensed CC0.

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