A genetic mutation found in animals that live at high altitudes, such as yaks and Tibetan antelopes, may offer new ways to repair nerve damage in conditions like cerebral paralysis and multiple sclerosis (MS), according to a March 13 report in the journal Neuron. The study reveals a naturally occurring pathway that could support regeneration after nerve injury by using molecules already present in the human body.
The research is significant because it points to potential treatments for diseases where the myelin sheath—the protective layer around nerve fibers—is damaged. Damage to this sheath can disrupt nerve signals and lead to neurological problems. In newborns, low oxygen during brain development can harm the myelin sheath, causing cerebral paralysis. In adults, MS results from the immune system attacking this layer, while reduced blood flow due to aging can also cause myelin damage and contribute to conditions like vascular dementia.
Corresponding author Liang Zhang of Songjiang Hospital Affiliated to Shanghai Jiao Tong University School of Medicine said, "Evolution is a great gift from nature, providing a rich diversity of genes that help organisms adapt to different environments. There is still so much to learn from naturally occurring genetic adaptations."
Previous studies showed that animals on the Tibetan Plateau carry a mutation on the Retsat gene, which may help them maintain healthy brain function despite low oxygen levels. Zhang's team tested whether this mutation could protect against myelin sheath damage by exposing newborn mice with and without the mutation to low-oxygen conditions similar to those at high elevations. Mice with the Retsat mutation performed better on learning and memory tests and had more myelin around their nerve fibers than those without it.
Further experiments revealed that mice with the Retsat mutation recovered faster from myelin injuries similar to those seen in MS. These mice also had more mature oligodendrocytes—cells responsible for producing myelin—and higher levels of ATDR, a metabolite derived from vitamin A. When ATDR was given directly to mice with an MS-like disease, their symptoms improved.
Zhang said current MS treatments mainly focus on suppressing immune activity but added: "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." The research received support from several Chinese science foundations and programs.
