“Evolution is a great gift from nature, providing a rich diversity of genes that help organisms adapt to different environments,” says corresponding author Liang Zhang of Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine. “There is still so much to learn from naturally occurring genetic adaptations.”

Why Myelin Damage Matters for Brain Health

The myelin sheath is a protective coating that surrounds nerve fibers in the brain and spinal cord. It plays a critical role in ensuring that electrical signals travel quickly and efficiently. When oxygen levels are too low during early brain development, this protective layer can be damaged, which may lead to cerebral paralysis in newborns.

In adults, damage to myelin is a defining feature of MS, an autoimmune disorder in which the immune system attacks this protective layer. Reduced blood flow to the brain, which becomes more common with age, can also harm myelin and contribute to conditions such as cerebral small vessel disease and vascular dementia.

High-Altitude Mutation in the Retsat Gene

Earlier research showed that animals living on the Tibetan Plateau, which has an average elevation of 14,700 feet, carry a mutation in a gene known as Retsat. Scientists have long suspected that this change helps these animals maintain healthy brain function despite living in chronically low-oxygen environments.

To test this idea, Zhang and his team examined whether the mutation could protect the myelin sheath. They exposed newborn mice to low-oxygen conditions similar to altitudes above 13,000 feet for about a week. Mice carrying the Retsat mutation outperformed those without it in tests measuring learning, memory, and social behavior. Their brains also showed higher levels of myelin around nerve fibers.

Faster Myelin Repair and Nerve Regeneration

The researchers then explored whether the mutation could help repair existing myelin damage similar to what occurs in MS. In mice with the mutation, damaged myelin recovered more quickly and more completely. The affected areas also contained greater numbers of mature oligodendrocytes, the cells responsible for producing myelin.

Vitamin A Metabolite ATDR Boosts Brain Repair

Further analysis revealed that mice with the mutation produced increased levels of ATDR, a metabolite derived from vitamin A, in their brains. The mutation appears to enhance the activity of enzymes that convert vitamin A into its active forms. These metabolites support the growth and maturation of oligodendrocytes, which in turn helps rebuild the myelin sheath.

When researchers administered ATDR to mice with an MS-like condition, the animals showed reduced disease severity and improved motor function.

A Potential New Approach to Treating MS

Current therapies for MS largely aim to control immune system activity. Zhang suggests this discovery could point to a different strategy. “ATDR is something everyone already has in their body. Our findings suggest that there may be an alternative approach that uses naturally occurring molecules to treat diseases related to myelin damage,” he says.

The study was supported by the National Science and Technology Major Project, the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, Shanghai Post-doctoral Excellence Program, the Natural Science Foundation of Shanghai, the 2024 Tibet Autonomous Region Science and Technology Plan Key R&D and Transformation Project, the Open Research Fund of Navy Medical University Basic Medical College, Yunnan Revitalization Talent Support Program Science & Technology Champion Project and the Yunnan Revitalization Talent Support Program.