Yaks could hint at a way to treat brain diseases like MS

A brain repair kit that helps yaks and other animals naturally cope with low oxygen levels at high altitudes could pave the way for a new way to treat brain diseases such as multiple sclerosis. In mice with brain lesions mimicking MS, the tools in the kit decreased signs of damage in young mice exposed to low oxygen and improved MS symptoms in adult mice, researchers report March 13 in Neuron.

Previous research has found that animals living on the Tibetan plateaulike yaks and antelopes, carry a mutation in a gene called Resumption. Their plains counterparts do not have this mutation, leading scientists to suspect that it helps protect the brain in low-oxygen environments.

“People usually think it’s due to better lung capacity, but I wondered if evolutionary adaptation changed the brain,” says Liang Zhang, a neuroscientist at Shanghai Jiao Tong University. He was particularly intrigued by the fact that these animals had normal white matter in their brains.

White matter makes up about half of the brain; it is made up of bundles of nerve fibers that allow different regions of the brain to communicate. This neural wiring is wrapped in myelin, a fatty substance that ensures that nerve fibers conduct signals efficiently. In MS, the immune system attacks myelinleading to neurological symptoms and problems with balance and coordination.

Myelin production requires a lot of energy, which the brain gets from oxygen. Low oxygen levels, called hypoxia, can therefore disrupt myelination. During gestation, such disturbances can lead to conditions such as cerebral palsy in newborns.

To find out if Retsat plays a role in protecting brain health, Zhang and his colleagues placed the young mice in a low-oxygen environment comparable to the thin air at 5,800 meters above sea level for a week. Mice engineered to undergo the genetic mutation performed better than normal mice on tests of learning, memory and social behavior, and had more myelin in their brains.

In a separate test, adult mice with the mutation regenerated myelin better than mice without the mutation and had more mature oligodendrocytes, the brain cells that produce myelin. The experiments revealed that the Retsat The gene helps neurons convert a vitamin A-related molecule called ATDR into a form called ATDRA, which triggers the creation of mature oligodendrocytes.

When young mice exposed to low oxygen were injected with ATDR and ATDRA, both molecules reduced the impact of hypoxia on myelin in the brain. Giving ATDR to adult mice with MS-like brain damage significantly improved their symptoms.

“It’s beautiful science, but there’s a long way to go before it happens to humans,” says Anna Williams, a neurologist at the University of Edinburgh, who was not involved in the study.

Current treatments for MS aim to slow the progression of the diseasemainly by suppressing the immune system. Finding ways to repair existing nerve damage has proven more difficult. Researchers are working on ways to regenerate myelin and a drug is in early clinical trials. But an earlier drug that increases levels of mature oligodendrocytes using the same molecular switch as ATDRA caused serious side effectsthe researchers therefore stopped pursuing this path.

It’s unclear whether molecules already in the body will fare better. “It may be safer than [a drug]but we don’t know what concentration is needed for repair,” says Zhang. “ATDR has many functions, so we need to pay attention to side effects.”

If the approach proves safe, it could help treat conditions involving myelin damage, including all neurodegenerative diseases, even stroke. This discovery shows the power of looking to nature for clues about how evolution solves challenges, Zhang says. “We can discover many secrets from evolutionary adaptations that we can use for medical conditions.”