# Altered Diversity of Astrocyte sub-types and Signaling Capabilities in Alzheimer's Disease

> **NIH NIH R21** · UNIV OF NORTH CAROLINA CHAPEL HILL · 2021 · $233,250

## Abstract

Project Summary/Abstract
Alzheimer’s Disease (AD) has been identified as one of the highest priority neurobiological diseases in need of
research advancement, inflicting progressive cognitive impairment on patients, and excessive burden on
caregivers and families. Due to the lack of effective preventative or reparative treatments for AD, it is imperative
to identify cellular or circuit factors contributing to the impairments in learning and memory. It has long been
observed that glial cells are noticeably altered, morphologically and molecularly, under conditions of
neurodegeneration and inflammation, including in AD. Astrocytes in particular have critical roles in synaptic
function, integration of circuit responses, and network homeostasis. It is yet unclear how activity-dependent
dynamics of intracellular signaling in these cells are altered under disease conditions.
Due to the anatomical importance of the dentate gyrus, the heterogeneous signaling characteristics of
hippocampal astrocytes, and the involvement of inflammatory processes in AD, we postulate that: dentate gyrus
astrocytes maintain diverse signaling capabilities in response to distinct neuronal circuit activation, and
that these signals are differentially vulnerable to AD pathology.
Using selective circuit stimulation and membrane-tagged calcium imaging in two distinct populations of
astrocytes of the dentate gyrus, we will investigate the capabilities and susceptibilities of astrocyte responses to
neurotransmission and neuromodulation. Adaptation of calcium datasets to new computational analysis toolsets
specifically designed for the unique characteristics of astrocyte signaling will be used to categorize and profile
capabilities of hilar and molecular layer astrocytes in control animals and in the 5xFAD animal model of AD.
Furthermore, we shall attempt to identify astrocyte sub-populations and alterations in astrocyte diversity within
the dentate gyrus, using single-cell sequencing, cluster analysis, and examination of differentially expressed
genes and pathways. In this way, we will define the susceptible sub-populations of astrocytes in AD, and reveal
alterations in gene expressions in these critically important cells as they undergo pathology-related modifications.
Results from this study will greatly inform on the potential of targeting specific subsets of astrocytes in
development of AD therapies, and will provide a database of transcript levels by which to measure effectiveness
of potential interventions.

## Key facts

- **NIH application ID:** 10301864
- **Project number:** 1R21AG074293-01
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **Principal Investigator:** BRENT ASRICAN
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $233,250
- **Award type:** 1
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10301864

## Citation

> US National Institutes of Health, RePORTER application 10301864, Altered Diversity of Astrocyte sub-types and Signaling Capabilities in Alzheimer's Disease (1R21AG074293-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10301864. Licensed CC0.

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