# Epigenetic modulation of purinergic signaling in microglia

> **NIH NIH R03** · UNIVERSITY OF NORTH DAKOTA · 2020 · $70,500

## Abstract

In the brain, the innate immune response is initiated by microglia and amplified by astrocytes, which through
glial communication act to propagate the neuroinflammatory response. It is well known that adenosinergic
signaling is ubiquitous to the brain yet is immerging as a key regulatory mechanism that can be utilized to
disrupt neuroglial communication and reduce neuroinflammation. Both microglia and astrocytes possess
adenosinergic receptors and express the enzymes that metabolize extracellular ATP and adenosine which in
turn modulate adenosinergic and inflammatory signaling. Because adenosine can influence neuronal activity
and modulate neuroinflammation, being able to modulate adenosine levels or the receptors involved in
adenosinergic signaling has a broad therapeutic potential. However, the link between acetate-induced
epigenetic changes in purinergic protein expression is not well understood. Based on these studies we
propose the hypothesis that increasing acetate metabolism, via increases in histone acetylation, will modulate
purinergic signaling in microglia promoting an anti-inflammatory phenotype. To test this hypothesis we will
complete following two aims (1) to determine the mechanism(s) by which acetate alters purine metabolism and
(2) to determine the functional effect that acetate-induced changes in purinergic signaling have on
inflammatory phenotype. Our working hypothesis is that acetate-induced changes in purinergic signaling will
confer an anti-inflammatory phenotype my modulating histone acetylation. By describing how energy
supplementation can influence the expression of enzymes and receptors involved in purinergic signaling is
important to understand the therapeutic mechanism of acetate supplementation. The innovative of this study is
to determine the epigenetic link between an increase in acetyl-CoA metabolism, alterations in purinergic
signaling, and its functional effect on inflammatory phenotype.

## Key facts

- **NIH application ID:** 9958670
- **Project number:** 1R03AI152213-01
- **Recipient organization:** UNIVERSITY OF NORTH DAKOTA
- **Principal Investigator:** THAD Allen ROSENBERGER
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $70,500
- **Award type:** 1
- **Project period:** 2020-03-06 → 2022-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9958670

## Citation

> US National Institutes of Health, RePORTER application 9958670, Epigenetic modulation of purinergic signaling in microglia (1R03AI152213-01). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9958670. Licensed CC0.

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