# Mitochondrial Mechanisms of Astrogliosis in Epilesy

> **NIH NIH R37** · UNIVERSITY OF COLORADO DENVER · 2022 · $508,654

## Abstract

Project Summary
Neuroinflammation has been identified as a therapeutic target for acquired epilepsy. However, if and how
mitochondria contribute to neuroinflammatory processes such as astrogliosis remains unknown. The goal of
this proposal is to determine if mitochondrial reactive oxygen species (mtROS) generated within neurons can
activate astrogliosis. This non-cell autonomous regulation is hypothesized to occur by posttranslational redox
modification of glial fibrillary acidic protein (GFAP) resulting in long-lasting neuroinflammation and epilepsy. To
test this idea, we plan to utilize a combination of tools and approaches including embryonic and inducible
mouse models lacking mitochondrial superoxide dismutase in forebrain neurons, 2-photon imaging of
astrocytic calcium, mitochondria-specific models, and mass spectrometry. The following specific aims will be
explored. Specific Aim 1: Determine if mitochondrial oxidative stress is sufficient to increase astrogliosis in
vitro. Specific Aim 2: Determine the role of neuronal mtROS in GFAP upregulation and astrogliosis in vivo.
Specific Aim 3. Determine the role of mtROS in GFAP upregulation, astrogliosis, epilepsy and/or cognitive
dysfunction in chemoconvulsant epilepsy models. Potential clinical application of the proposal includes
identification of novel metabolism-based therapies to target astrogliosis in epilepsy.

## Key facts

- **NIH application ID:** 10520563
- **Project number:** 2R37NS039587-19
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MANISHA N PATEL
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $508,654
- **Award type:** 2
- **Project period:** 1999-12-01 → 2026-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10520563

## Citation

> US National Institutes of Health, RePORTER application 10520563, Mitochondrial Mechanisms of Astrogliosis in Epilesy (2R37NS039587-19). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10520563. Licensed CC0.

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