# The Role of Astrocytes in the Fragile X Pathogenesis

> **NIH NIH R01** · UNIVERSITY OF NEBRASKA MEDICAL CENTER · 2020 · $457,265

## Abstract

Fragile X syndrome (FXS) is the most common form of inherited intellectual disability
and one of the main identified genetic causes of autism spectrum disorder. Astrocytes, a
type of glial cells, perform multiple tasks in the brain and have been implicated in
regulating synaptic development, function and plasticity. Yet the role astrocytes play in
neurodevelopmental disorders is not well understood. In this proposal, we aim to identify
the contribution of astroglial Fragile X Mental Retardation Protein (FMRP) to altered
astrocyte Ca2+ signaling, synaptic deficits and cortical plasticity impairments associated
with FXS. We approach this through three aims which utilize mouse genetics, in vivo
imaging of Ca2+ signaling and synaptic protein trafficking, cell and molecular techniques
and mouse behavior. In Aim 1, we will study the role of FMRP in regulating astrocytic
Ca2+ signaling. We will perform in vivo imaging of astrocytic Ca2+ signaling in awake fmr1
KO mice and in transgenic mice in which FMRP is selectively deleted or exclusively
expressed in astrocytes. In Aim 2, we will examine mechanisms of altered astrocytic
Ca2+ signaling in FXS with cell, molecular and pharmacologic experiments. In Aim3, we
will examine if loss of FMRP in astrocytes results in basal and learning-induced
alterations in functional and structural synaptic plasticity by electrophysiology and in vivo
imaging of tagged AMPAR trafficking in dendritic spines, in astrocyte-specific FMRP
knockout mice. This work is expected to provide important knowledge about the role of
astrocytes in FXS and has the potential to identify novel therapeutic targets for FXS.

## Key facts

- **NIH application ID:** 9833537
- **Project number:** 5R01NS109381-02
- **Recipient organization:** UNIVERSITY OF NEBRASKA MEDICAL CENTER
- **Principal Investigator:** Anna Dunaevsky
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $457,265
- **Award type:** 5
- **Project period:** 2019-01-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9833537

## Citation

> US National Institutes of Health, RePORTER application 9833537, The Role of Astrocytes in the Fragile X Pathogenesis (5R01NS109381-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9833537. Licensed CC0.

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