# A new combinatorial strategy to selectively manipulate reactive astrocytes in disease

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA RIVERSIDE · 2020 · $184,759

## Abstract

PROJECT SUMMARY
Common to virtually all neurodegenerative diseases and brain disorders are changes in a glial cell type
called an astrocyte, which become “reactive”. Astrocytes ordinarily provide critical support for neurons
and only turn into reactive astrocytes (RAs) following injury or development of disease. A longstanding
issue which has remained unknown is whether RAs contribute to, or help alleviate, disease progres-
sion. Our long-term goal is to increase understanding of the molecular and cellular underpinnings of
diseases and disorders of the nervous system through increased understanding of the role of reactive
astrocytes. The objective of this proposal is to deliver a new strategy to selectively alter (eliminate, in-
crease, or decrease) the function of only RAs at any point in the progression of nervous system disor-
ders. One such disorder for which new treatments are needed is epilepsy. Despite being the third most
common neurological disorder in the U.S. after Alzheimer’s disease and stroke, epilepsy is among the
least understood of the major chronic medical conditions. Two aims are proposed, with the goal of
characterizing this new strategy and providing proof-of-principle for using the approach for the selective
manipulation of RAs in disease: In Aim 1, we will first characterize a novel reactive astrocyte inducible
Cre transgenic strategy to selectively manipulate RAs in brain disease. In Aim 2, we will then use the
new approach to either selectively eliminate RAs or reprogram them back into non-reactive astrocytes
at various stages during the development of epilepsy. Our work will provide new knowledge on the pro-
tective vs. detrimental roles of reactive astrocytes in the development of epilepsy. The rationale for the
proposed research is that new insight into the role of reactive cell types in disease is an important goal
for the development of more efficacious treatments. We anticipate that this research will be transforma-
tive, as we will introduce to the research community a powerful new strategy to investigate the role of
reactive astrocytes in any disease or disorder of the nervous system.

## Key facts

- **NIH application ID:** 9890020
- **Project number:** 5R21NS109918-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA RIVERSIDE
- **Principal Investigator:** Todd A Fiacco
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $184,759
- **Award type:** 5
- **Project period:** 2019-04-01 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9890020

## Citation

> US National Institutes of Health, RePORTER application 9890020, A new combinatorial strategy to selectively manipulate reactive astrocytes in disease (5R21NS109918-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/9890020. Licensed CC0.

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