# Exploring the role of reactive astrocytes in brain inflammation using a novel combinatorial strategy

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2021 · $424,943

## Abstract

PROJECT SUMMARY
While numerous transgenic tools and approaches exist to enable manipulation of gene expression in
many cell types in the healthy brain, tools designed to target and study cells present only in the dis-
eased or damaged brain are lacking. Common to virtually all neurodegenerative diseases, brain injuries
and infections is a neuroinflammatory and immune response characterized by changes in astrocytes,
which become “reactive”. Astrocytes ordinarily provide critical support for neurons and only turn into
reactive astrocytes (RAs) in brain disease and inflammation. A longstanding issue which has remained
unknown is whether RAs contribute to or help alleviate disease progression. The objective of this appli-
cation is to deliver a new combinatorial transgenic strategy and toolkit to specifically target RAs in dis-
ease. This toolkit will enable researchers to selectively alter (eliminate, increase, or decrease) gene ex-
pression only in RAs at any point in the progression of brain disease and inflammation. Brain infection
by the parasite Toxoplasma gondii will serve as a model of brain inflammation stemming from infection.
Three aims are proposed: In Aim 1, we will first characterize the Cre transgenic strategy to selectively
manipulate gene expression only in RAs in brain disease. In Aim 2, we will then use the new approach
to selectively ablate, prevent, or reprogram RAs back into non-reactive astrocytes at various stages
during the acute and chronic inflammatory process. Our work will provide new information on the role of
reactive astrocytes in the early vs. sustained stages of brain inflammation. In Aim 3, we will perform
“translatome” analysis to identify genes uniquely altered in reactive astrocytes during brain inflamma-
tion for the first time, providing novel targets for future study. Our innovative approach will allow detec-
tion of both inductions and reductions in gene expression with unprecedented signal-to-noise over ex-
isting approaches. The rationale for the proposed research is that improving understanding of the cellu-
lar and molecular mechanisms of brain disease will provide novel insights into the development of more
effective treatments. We anticipate that this research will be transformative, as we will introduce to the
research community a powerful new strategy to investigate the role of reactive cell types in any disease
or disorder of the nervous system.

## Key facts

- **NIH application ID:** 10169400
- **Project number:** 5R01DA048815-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Todd A Fiacco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $424,943
- **Award type:** 5
- **Project period:** 2019-08-01 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10169400

## Citation

> US National Institutes of Health, RePORTER application 10169400, Exploring the role of reactive astrocytes in brain inflammation using a novel combinatorial strategy (5R01DA048815-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10169400. Licensed CC0.

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