# Stabilizing Brain Function via Glial Epigenetic Signaling

> **NIH NIH R01** · GEORGETOWN UNIVERSITY · 2022 · $342,097

## Abstract

Abstract
Homeostatic signaling systems operate as protective mechanisms at the level of individual synapses, neurons,
and neural circuits to stabilize brain function and animal behavior. Defective homeostatic regulation causes
synapse and neural network instability, which is associated with multiple chronic neural disorders, such as
epilepsy, autism and Alzheimer's Disease. Glia are key players that control many different aspects of neural
development and synaptic function and are increasingly linked to neurodevelopmental and neurodegenerative
pathology. However, virtually nothing is known about whether and how glial signaling is involved in modulating
presynaptic neurotransmitter release in synaptic homeostasis. Our preliminary data in Drosophila suggest that
impairment of glial signaling completely abolishes presynaptic homeostasis when the nervous system is
challenged by acute or long-term synaptic perturbations. We demonstrate that glia respond to chronic inhibition
of postsynaptic glutamate receptor sensitivity by modulating their histone acetylation codes. Through a genetic
screen in Drosophila, we identified genes that function specifically in glia for the induction and sustained
expression of presynaptic homeostasis. Our preliminary data emphasize the importance of epigenetic
mechanism-mediated glial signaling in stabilizing synaptic function. We propose to fill the mechanistic gap of
understanding the glial signaling in stabilizing the brain function. We will systematically study how the interactions
between glia and neuron affect synaptic transmission and synapse stability by using a wide array of genetic,
molecular, cellular, electrophysiological, imaging and bioinformatic approaches. We will further extend our
studies to mouse hippocampal cultures to examine how astrocyte-expressed epigenetic regulators modulate
presynaptic calcium influx, neurotransmitter vesicle pool size and neurotransmitter release. Understanding the
function of glial-derived molecules in stabilizing the nervous system confronting chronic harmful stimuli will
benefit the development of new treatments and potential therapeutics for neural disorders caused by synapse
instability.

## Key facts

- **NIH application ID:** 10438708
- **Project number:** 5R01NS117372-03
- **Recipient organization:** GEORGETOWN UNIVERSITY
- **Principal Investigator:** Tingting Wang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $342,097
- **Award type:** 5
- **Project period:** 2020-07-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10438708

## Citation

> US National Institutes of Health, RePORTER application 10438708, Stabilizing Brain Function via Glial Epigenetic Signaling (5R01NS117372-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10438708. Licensed CC0.

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