A genetic alteration that enables creatures such as yaks and Tibetan antelopes to thrive at elevated altitudes might hold the key to repairing nerve damage associated with conditions like cerebral palsy and multiple sclerosis (MS). Findings from a study published in the journal Neuron unveil a natural process that encourages nerve repair following injury, potentially opening novel avenues for treating illnesses like MS by leveraging molecules already present within the human body.
“Evolution is a wonderful gift from nature, providing a wealth of genes that aid organisms in adapting to diverse environmental situations,” states Liang Zhang, the study’s lead author from Songjiang Hospital, part of the Shanghai Jiao Tong University School of Medicine. “There remains much to uncover about these inherent genetic adaptations.”
The myelin sheath is a protective covering encircling nerve fibers in the brain and spinal cord, crucial for efficient transmission of nerve signals. Oxygen deprivation during brain development can compromise this sheath, leading to ailments such as cerebral palsy in newborns.
In adults, damage to the myelin sheath is linked to multiple sclerosis, an autoimmune disorder where the body’s immune system mistakenly targets and degrades the myelin. Reduced blood flow to the brain, often accompanying aging, can also injure myelin, contributing to conditions like cerebral small vessel disease and vascular dementia.
Prior research identified that animals inhabiting the Tibetan Plateau, which averages 14,700 feet in elevation, possess a mutation in a gene termed Retsat. Scientists hypothesized that this mutation assists animals like yaks and Tibetan antelopes in maintaining sound brain function despite sustained low oxygen levels.
Zhang and his colleagues sought to determine if this mutation could prevent myelin sheath damage. They exposed newborn mice to oxygen-deprived conditions equivalent to over 13,000 feet for roughly a week.
Mice carrying the Retsat mutation performed markedly better in tests assessing learning, memory, and social interaction compared to mice with the standard version of the gene. Brain analysis further revealed that mice engineered with the high-altitude variant exhibited higher levels of myelin surrounding their nerve fibers.
Subsequently, the researchers investigated whether the Retsat mutation could restore myelin sheath damage similar to that seen in MS. They observed that mice possessing this mutation regenerated their myelin sheath much more rapidly and completely following an induced injury. Furthermore, affected areas showed an increased presence of mature oligodendrocytes—the cell type responsible for myelin production.
Further investigation indicated that mice with this mutation had elevated levels of ATDR in their brains, a metabolite derived from Vitamin A.
The Retsat mutation appears to boost the enzymatic activity that converts Vitamin A into its metabolites, which in turn promotes the development and maturation of myelin-producing oligodendrocytes. When the research team administered ATDR to mice exhibiting an MS-like condition, disease severity decreased, and their motor function improved.
As Zhang points out, current MS therapies primarily focus on suppressing immune system activity. “ATDR is something already present in every human body. Our findings suggest there might be an alternative strategy, utilizing natural molecules to address diseases related to myelin damage,” he concludes.
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