# Determining the neuroprotective role of estriol in experimental autoimmune encephalomyelitis

> **NIH NIH F31** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2020 · $32,736

## Abstract

Project Abstract
 Multiple Sclerosis (MS) is an autoimmune disorder characterized by inflammation, demyelination, and
neurodegeneration. Despite wide symptomatic variability, gray matter (GM) atrophy has consistently emerged
as a strong indicator of clinical disability. In fact, evidence suggests progressive loss of GM correlates with
disability and cognitive dysfunction better than many other magnetic resonance imaging biomarkers of MS,
including enhancing lesions and lesion burden. While 40-70% of patients experience cognitive decline over the
course of disease, there is no treatment on the market that can halt the progression of GM atrophy or cognitive
decline. Current treatment options are primarily designed to reduce inflammation and have had only modest
success at slowing GM atrophy in MS. Treatment with the sex hormone estriol has been shown to reduce
relapses and preserve GM in both MS and in experimental autoimmune encephalomyelitis (EAE), its most
commonly used mouse model. Recently, in a clinical trial with female MS patients, estriol treatment was shown
to reduce GM atrophy and improve performance in cognitive testing. The mechanisms underlying the
neuroprotective effects of estriol remain unclear. Understanding how estriol is working to preserve GM tissue
may lead to the development of better neuroprotective therapies for patients with MS and potentially other
neurodegenerative conditions. Our preliminary data suggest that estriol treatment in EAE reduces GM atrophy
and neuronal loss in the cerebral cortex and prevents axonal transection in the spinal cord. Further, we have
found that axonal transection in the spinal cord is correlated with GM volume almost exclusively in the motor
and sensory motor cortices. In this proposal, I will utilize the EAE mouse model to 1) identify regions where
estriol treatment preserves GM volume and what changes in pathology are associated with GM preservation,
2) characterize the effect of estriol on oxidative stress in mitochondria, and 3) identify genes differentially
expressed in cortical neurons from estriol-treated animals. This project will provide invaluable information
about how estriol provides neuroprotection in GM and will highlight potential targets for future neuroprotective
therapies.

## Key facts

- **NIH application ID:** 9991944
- **Project number:** 5F31NS105387-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Cassandra Eve Meyer
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $32,736
- **Award type:** 5
- **Project period:** 2018-09-01 → 2021-05-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9991944

## Citation

> US National Institutes of Health, RePORTER application 9991944, Determining the neuroprotective role of estriol in experimental autoimmune encephalomyelitis (5F31NS105387-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9991944. Licensed CC0.

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