# Dysregulated intracellular calcium in microglia during Alzheimer's disease

> **NIH NIH K01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 2022 · $113,454

## Abstract

Project Summary
Microglia, the immune cells of the brain, perform essential homeostatic functions including debris clearance by
phagocytosis and maintenance of neurons by release of growth factors and other molecules. However, during
Alzheimer’s disease (AD), microglia accumulate near amyloid plaques where they acquire an activated
phenotype, lose their homeostatic phenotype, and take on an activated phenotype that can induce
neurotoxicity. Intracellular calcium in microglia regulates their transformation from this homeostatic resting
state to an activated immune-effector state. Microglia intracellular calcium orchestrates functions such as
phagocytosis, proliferation, migration, generation of neurotrophic factors, cytokine production and release, and
formation of neurotoxic reactive oxygen species. Intracellular calcium dysregulation appears in activated, non-
homeostatic microglia near amyloid β (Aβ) plaques in mouse models of AD. Our overall hypothesis that
dysregulated intracellular calcium shifts microglia phenotype in AD. Our preliminary data suggest that blocking
L-type voltage dependent calcium channels (L-VDCCs) can shift microglia towards a more homeostatic
phenotype. The proposed experiments test the hypothesis that L-VDCCs can drive microglia calcium
dysregulation during AD pathology. We will test this by using pharmacological antagonism of L-VDCCs
combined with genetic ablation of microglia-specific L-VDCCs in the presence of AD pathology to define the
role of L-VDCCs on microglia phenotype and function. For the training aspect of this proposal, we will use 1) in
vivo multiphoton imaging to assess microglia function and calcium dynamics and 2) single-nuclei RNA
sequencing to define the cell-specific effects of L-VDCC antagonism in vivo. If our hypothesis is correct, L-
VDCC function will be a mechanistic link microglia calcium dysregulation and microglia functional phenotype
during AD. This finding would be relevant to numerous age-associated neurodegenerative disorders where
changes in microglia phenotype are observed.

## Key facts

- **NIH application ID:** 10418623
- **Project number:** 5K01AG066747-03
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **Principal Investigator:** Sarah Christine Hopp
- **Activity code:** K01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $113,454
- **Award type:** 5
- **Project period:** 2020-04-15 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10418623

## Citation

> US National Institutes of Health, RePORTER application 10418623, Dysregulated intracellular calcium in microglia during Alzheimer's disease (5K01AG066747-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10418623. Licensed CC0.

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