# Redox Control of Seizure-Induced Neuroinflammation

> **NIH NIH R01** · UNIVERSITY OF COLORADO DENVER · 2021 · $23,445

## Abstract

Mitochondrial Reactive Oxygen Species in Epilepsy-Associated Astrogliosis
The parent grant focuses on the interplay between neuroinflammation and redox status. The
supplemental research addresses a related but distinct goal to investigate the role of
mitochondria in seizure-induced neuroinflammation. Mitochondria integrate the energy
requirements of neuronal cells and circuits with nutrients, ions, inflammatory mediators and
redox status. Mitochondrial dysfunction, oxidative stress and neuroinflammation have been
linked with pathophysiological hyperexcitability associated with epilepsy. Neuroinflammation
specifically has been identified as a therapeutic target for epilepsy, however the detailed
mechanisms underlying seizure-induced neuroinflammation, including upregulation of astrocyte-
specific glial fibrillary acidic protein (GFAP), remain at large. One clue regarding upregulation of
GFAP arises from recent studies in our laboratory showing a robust transcriptional upregulation
of GFAP in mice lacking the anti-oxidant mitochondrial manganese superoxide dismutase-2
(Sod2) in forebrain neurons, a finding replicated in primary neuronal-glial culture. In contrast,
mixed cultures in which neurons were selectively depleted displayed no such upregulation. The
goal of this project is to determine if mitochondrial reactive oxygen species (mtROS) generated
within neurons can activate neuroinflammation via upregulation of GFAP expression as a result
of posttranslational redox modification of a conserved cysteine (Cys294) in GFAP, resulting in
long-lasting neuroinflammation. Aim 1 will determine if neuronal mtROS is sufficient to induce
GFAP upregulation and astrogliosis in vitro using mixed rat neuronal culture and in vivo using
Nex-Cre/Sod2f/f mice microinjected with viral vectors driving GCaMP6f within astrocytes. Aim 2
will determine if this astrogliosis involves redox modification of GFAP protein by mutating
Cys294. These studies will reveal novel redox-based therapeutic targets to treat epilepsy.

## Key facts

- **NIH application ID:** 10302913
- **Project number:** 3R01NS086423-06S1
- **Recipient organization:** UNIVERSITY OF COLORADO DENVER
- **Principal Investigator:** MANISHA N PATEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $23,445
- **Award type:** 3
- **Project period:** 2013-09-30 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10302913

## Citation

> US National Institutes of Health, RePORTER application 10302913, Redox Control of Seizure-Induced Neuroinflammation (3R01NS086423-06S1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10302913. Licensed CC0.

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