# Interferon-gamma mediates neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy (MSA)

> **NIH NIH K00** · YALE UNIVERSITY · 2024 · $86,190

## Abstract

Multiple system atrophy (MSA) is a fatal, progressive neurodegenerative disease that is characterized by
demyelination in the corpus callosum and putamen due to the accumulation of alpha synuclein (α-syn) in glial
cytoplasmic inclusions (GCI) within the oligodendrocytes. Previous data has shown that in post-mortem MSA
brain, α-syn pathology is accompanied by MHCII expression and increased infiltration of peripheral T cells
(CD4+). IFNγ released from CD4+ T cells enhances inflammation by binding to its receptor (IFNγR1) and,
through the JAK/STAT pathway, activates MHCII antigen presentation. Other studies have shown, the
neuroinflammation found in post-mortem tissue from MSA patients can be modeled in rodents through a modified
AAV, Olig001-SYN which has a high tropism (>95%) for oligodendrocytes. Moreover, the Oligo001-SYN rodent
model of MSA shows a similar robust CD4+ T cell response due to the oligodendrocyte α-syn expression. My
preliminary results showed there was significant neuroinflammation via increase in IFNɣ and MHCII expression
in the Olig001 mouse model. Additionally, when IFNɣ was knocked down there was a significant reduction in
overall MHCII expression and general neuroinflammation and demyelination. IFNɣ is required for
neuroinflammation and demyelination, however the cell specificity of IFNɣ remains unclear. Therefore, findings
from this proposal can address if Th1 cells (CD4+ T cells that produce IFNɣ) are required for MSA pathology.

## Key facts

- **NIH application ID:** 10856291
- **Project number:** 4K00NS129106-02
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Nicole Corbin-Stein
- **Activity code:** K00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $86,190
- **Award type:** 4N
- **Project period:** 2023-07-20 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10856291

## Citation

> US National Institutes of Health, RePORTER application 10856291, Interferon-gamma mediates neuroinflammation, demyelination, and neurodegeneration in a mouse model of multiple system atrophy (MSA) (4K00NS129106-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10856291. Licensed CC0.

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