# Development and characterization of an AAV-based tool to functionally ablate astrocytic mitochondria in specific brain regions in vivo

> **NIH NIH R21** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 2022 · $227,250

## Abstract

PROJECT ABSTRACT
 Astrocytes are a group of glial cells with multiple roles in the brain. They extend fine processes that
localize near synapses and blood vessels and thus locally regulate synapse formation, elimination and
function, as well as blood-brain-barrier permeability. This local regulation more broadly impacts on the function
of larger neural circuits within the brain. Astrocytes from different brain regions show distinct morphological and
gene expression profiles, which suggest regional specificity of function. Links between neuronal degeneration,
distinctive of brain maladies such as Parkinson’s disease (PD) and Alzheimer’s disease (AD), and astrocytic
malfunction are suspected but not well characterized mechanistically.
 Mitochondria in astrocytes have recently emerged as specialized subcellular organelles with robust
spontaneous Ca2+ fluxes capable of responding to neurotransmitter agonists, a distinct functional proteomic
profile, and spatial segregation into somata versus processes with regard to Ca2+ fluxes and morphology.
These unique characteristics lead us to hypothesize that abnormalities in astrocytic mitochondria play a major
role in accelerating neurodegenerative processes in the brain. However, the lack of tools to functionally ablate
mitochondria selectively in astrocytes from specified brain regions in vivo is a major barrier towards defining
how astrocytic mitochondrial dysfunction contributes to neurodegeneration. Specifically, developing such a tool
would enable a mechanistic understanding of the role of astrocytic mitochondria in PD and AD. Here, we
propose to develop and characterize an adeno-associated virus (AAV)-based tool to functionally ablate
astrocytic mitochondria in two brain regions relevant to PD and AD, viz. the striatum and posterior cingulate
cortex, respectively. In addition, we will examine the cell-autonomous and non-cell autonomous effects of
functionally ablating astrocytic mitochondria on astrocytic and neuronal gene expression profiles with the future
goal of applying the knowledge gained to in vivo models of PD and AD.

## Key facts

- **NIH application ID:** 10371616
- **Project number:** 1R21NS121959-01A1
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **Principal Investigator:** MENDELL RIMER
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $227,250
- **Award type:** 1
- **Project period:** 2021-12-01 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10371616

## Citation

> US National Institutes of Health, RePORTER application 10371616, Development and characterization of an AAV-based tool to functionally ablate astrocytic mitochondria in specific brain regions in vivo (1R21NS121959-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10371616. Licensed CC0.

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