The genetic adaptations that allow animals such as yaks and Tibetan antelopes to survive in the absence of air may also point to new ways to repair nerve damage in humans. Researchers report that this mutation may help restore damaged nerve insulation in conditions such as cerebral palsy and multiple sclerosis (MS). This study was published in the Cell Press journal neuronwe have identified natural biological pathways that support neural regeneration and may be harnessed using molecules already present in the human body.
“Evolution is a great gift from nature, providing a variety of genes that help organisms adapt to different environments,” says corresponding author Liang Zhang of Songjiang Hospital, School of Medicine, Shanghai Jiao Tong University. “There is still much to learn from naturally occurring genetic adaptations.”
Why myelin damage is important for brain health
The myelin sheath is a protective membrane that surrounds nerve fibers in the brain and spinal cord. It plays an important role in ensuring that electrical signals are transmitted quickly and efficiently. If oxygen levels are too low during early brain development, this protective layer can be damaged, potentially leading to brain paralysis in newborns.
In adults, myelin damage is a hallmark feature of MS, an autoimmune disease in which the immune system attacks this protective layer. Reduced blood flow to the brain, which tends to occur with age, can also damage myelin and lead to conditions such as cerebral small vessel disease and vascular dementia.
High-altitude mutations in the Retsat gene
Previous research has shown that animals living on the Tibetan Plateau, which averages 14,700 feet above sea level, carry a mutation in a gene known as Resat. Scientists have long suspected that this change helps these animals maintain healthy brain function despite living in chronically hypoxic environments.
To test this idea, Zhang and his team investigated whether mutations could protect the myelin sheath. The researchers exposed newborn mice to hypoxic conditions similar to those at altitudes of more than 13,000 feet for about a week. Mice with the Retsat mutation performed better than mice without it on tests measuring learning, memory, and social behavior. Their brains also showed high levels of myelin around nerve fibers.
Faster myelin repair and nerve regeneration
The researchers then investigated whether this mutation could help repair pre-existing myelin damage similar to what occurs in MS. In mice with this mutation, damaged myelin recovered more quickly and completely. The affected area also contained large numbers of mature oligodendrocytes, the cells responsible for producing myelin.
Vitamin A metabolite ATDR promotes brain repair
Further analysis revealed that mice with this mutation produced increased levels of ATDR, a vitamin A-derived metabolite, in their brains. This mutation appears to enhance the activity of the enzyme that converts vitamin A into its active form. These metabolites support oligodendrocyte growth and maturation, which helps rebuild the myelin sheath.
When researchers administered ATDR to mice with MS-like symptoms, they found that the animals’ symptoms decreased in severity and their motor function improved.
Possibility of a new approach to MS treatment
Current treatments for MS primarily aim to control the activity of the immune system. Chan suggests the findings may point to another strategy. “ATDR is something we all already have in our bodies. Our findings suggest that there may be alternative approaches to using naturally occurring molecules to treat diseases associated with myelin damage,” he says.
This research was supported by the National Science and Technology Major Project, the National Natural Science Foundation of China, the China Postdoctoral Science Foundation, the Shanghai Postdoctoral Excellence Program, the Shanghai Natural Science Foundation, the 2024 Tibet Autonomous Region Science and Technology Plan Key Research, Development and Transformation Project, the Naval Medical College Basic Medical College Open Research Fund, the Science and Technology Champion Project of the Yunnan Provincial Revitalization Talent Support Program, and the Yunnan Provincial Revitalization Talent Support Program.
