# Defining Roles for Astrocyte Subpopulations in the Aging Brain

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $328,000

## Abstract

Summary
 Astrocytes are the most abundant type of glial cell in the CNS and play vital roles in all
facets of brain physiology. Recent studies from our lab identified five molecularly and
functionally distinct astrocyte subpopulations in the brain. One of these subpopulations is
specifically labeled by the cell surface maker CD51 and is endowed with enhanced
synaptogenic function, leading us to hypothesize that CD51+ astrocytes play an important role
in functioning brain circuits. To determine how CD51+ astrocytes contribute to circuit function,
we created a CD51-FLP mouse line that allows us selectively label and manipulate this
population of astrocytes in the brain. To decipher the mechanisms that regulate CD51+
astrocytes, we found that the transcription factor Sox9 is enriched in this subpopulation.
Preliminary studies in a newly generated mouse line that specifically eliminates Sox9 in
astrocytes revealed that this transcription factor selectively regulates astrocyte morphology and
circuit function in the hippocampus and olfactory bulb in an aging-dependent manner. Together,
these new mouse lines will enable us to uncover how CD51+ astrocytes regulate brain circuits
and reveal novel roles for Sox9 in controlling astrocyte diversity and function during aging.
 Based on the strength of these preliminary observations, we propose the following
specific aims. In specific aim 1, we will define the anatomical, morphological and physiological
properties of CD51+ and CD51- astrocytes in the aging brain and decipher how they contribute
to circuit function in the hippocampus and olfactory bulb. In specific aim 2, we will use our
astrocyte-specific Sox9 knockout mouse to decipher how it regulates astrocyte function in the
aging brain and how these changes in astrocytes impact circuit function in the hippocampus and
olfactory bulb. In specific aim 3 we will determine how Sox9 regulates astrocyte diversity during
aging and integrate our findings with Sox9 ChIP-Seq to decipher Sox9 target gene networks.

## Key facts

- **NIH application ID:** 10192033
- **Project number:** 1R01AG071687-01
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin Deneen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $328,000
- **Award type:** 1
- **Project period:** 2021-04-15 → 2026-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10192033

## Citation

> US National Institutes of Health, RePORTER application 10192033, Defining Roles for Astrocyte Subpopulations in the Aging Brain (1R01AG071687-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10192033. Licensed CC0.

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