# Transcriptional Control of Gliogenesis in the CNS

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2020 · $400,000

## Abstract

Abstract
The goal of the parent grant is to understand the transcriptional mechanisms that control the
physiological functions of astrocytes in the brain. The transcription factor Nuclear Factor I-A
(NFIA) is the focal point of the parent grant and we propose to determine its role in maintaining
astrocyte physiology and neuronal circuits across a host of brain regions. These topics are
particularly relevant to the pathogenesis of Alzheimer’s Disease (AD) as patients with AD have
reactive astrocytes closely associated with degenerating neurons across multiple brain regions;
these observations have been recapitulated in mouse models of AD. Despite these clear links
between AD pathology and astrocytes, evaluation of astrocyte phenotypes in AD typically
focuses on GFAP upregulation and various, poorly defined states of reactivity. These broad
molecular criteria overlook how pathological states manifest in AD disrupt normal astrocyte
function and their essential interactions with neurons during the formative stages of disease and
throughout progression. Therefore, the overarching goal of this supplement is to bring tools
developed in the parent grant to bear on mouse models of AD in order to decipher how
physiological changes in astrocytes contribute to AD pathogenesis.
 We have generated a set of mouse tools and developed a platform for comprehensively
evaluating astrocyte physiology and contributions to established circuits that we will apply to
mouse models of AD. In the first aim, we will decipher how astrocyte physiology and their
interactions with neurons change across of a series of landmark timepoints in mouse models of
AD. Here we will assess a battery of functional criteria including: morphology, Ca2+ activities,
proximity to neurons, handling of neurotransmitters, and activity of associated neurons. In the
second aim, we will use our mouse tools to evaluate the role of astrocytic NFIA in AD
pathogenesis. Using these tools, we discovered that astrocytic NFIA plays an essential role in
maintaining astrocyte function and regulating hippocampal circuits, a brain region that is
vulnerable to AD. Moreover, NFIA is highly expressed in reactive astrocytes found in human
neurological diseases. Using these observations as our premise, we will determine the
expression of NFIA in reactive astrocytes in human AD, how its loss modifies pathological
benchmarks of AD, and how AD modifies astrocytic NFIA function. Upon completion of this
supplement these studies will reveal when physiological changes in astrocytes take root during
AD pathogenesis and how NFIA contributes to these changes in astrocytes.

## Key facts

- **NIH application ID:** 10121324
- **Project number:** 3R01NS071153-11S1
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Benjamin Deneen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $400,000
- **Award type:** 3
- **Project period:** 2010-09-01 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10121324

## Citation

> US National Institutes of Health, RePORTER application 10121324, Transcriptional Control of Gliogenesis in the CNS (3R01NS071153-11S1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10121324. Licensed CC0.

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