# Astroglial mechanisms in sleep homeostasis

> **NIH NIH R01** · WASHINGTON STATE UNIVERSITY · 2021 · $382,494

## Abstract

Summary
Our parent grant NS114780 will determine cellular and molecular signaling pathways in astrocytes important in
mammalian sleep regulation. We now extend our approach to neurodegenerative diseases, with a focus on
mouse models of Alzheimer’s.
Sleep may play an important role in the etiology and progression of neurodegenerative disease. Abnormal
sleep is a common symptom of many neurodegenerative diseases including Alzheimer’s. Sleep also influences
several neurological processes that if perturbed may contribute to cognitive decline and dementia. Among
these are synaptic morphology/plasticity, immune response/neuroinflammation, brain metabolism and protein
clearance. Therefore, understanding how sleep and sleep loss impact the diseased brain may provide new
insights into Alzheimer’s and related diseases. This requires an understanding of how different classes of brain
cells operate during sleep.
The glial cells known as astrocytes are particularly important to examine in this context. Astrocytes mediate
several processes dysregulated in Alzheimer’s (e.g. synaptic pruning, neuronal metabolism and removal of
plaque proteins and are abnormally hyper-reactive in neurodegenerative disease (as measured by increased
intracellular Ca2+. Astrocyte hyper-reactivity may in turn disrupt these normal processes vital to brain function.
We have shown that astrocytes play central roles in mammalian sleep regulation. We have also recently
demonstrated that sleep normally reduces (clears) astrocyte intracellular Ca2+ concentrations that accumulate
during wakefulness [18]. We hypothesize that in Alzheimer’s the regulation of intracellular Ca2+ in astrocytes
during sleep is abnormal leading to astrocytic hyper-reactivity. We will test this hypothesis by
Impact: Sleep and astrocytes are implicated in neurodegenerative diseases like Alzheimer’s. Recent findings
from our laboratory indicate that astrocytes influence sleep. This indicates that astrocytes may mediate
important sleep functions that are relevant to neurodegenerative diseases. The requisite step to exploring this
possibility is to examine the activity of these glial cells during sleep in mouse models of neurodegenerative
disease. Our hypothesis is that sleep loss results in a persistent activation of astrocytes in neurodegenerative
disease, which in turn could lead to neuronal cell death. If true, our findings will be impactful because they will
identify a heretofore poorly understood interaction between sleep and glia that can be leveraged for new
therapeutic approaches to Alzheimer’s.

## Key facts

- **NIH application ID:** 10283928
- **Project number:** 3R01NS114780-01A1S1
- **Recipient organization:** WASHINGTON STATE UNIVERSITY
- **Principal Investigator:** MARCOS G FRANK
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $382,494
- **Award type:** 3
- **Project period:** 2021-04-01 → 2025-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10283928

## Citation

> US National Institutes of Health, RePORTER application 10283928, Astroglial mechanisms in sleep homeostasis (3R01NS114780-01A1S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10283928. Licensed CC0.

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