Mutations just happen – they are random and spontaneous. Sometimes they result in a new feature, which is an adaptation to the individual with the mutation. Animals that live in high altitude environments on the Tibetan Plateau (4 480 m above sea level) are adapted by having a mutation in the gene called Retsat. The theory is this mutation helped yaks and antelopes living at high altitude adapt to their long-term exposure to low oxygen concentrations by maintaining normal brain function.

Axons can be insulated by the myelin sheath. It is a protective coating and allows for saltatory conduction of action potentials. The action potential only occurs at the nodes of Ranvier. The diffusion of sodium ions into the axon results in a change in charge making the axon membrane depolarised. Sodium ions, now in a high concentration, diffuse to a place a lower concentration, which sets up an elongated local current between the nodes. This instantaneously causes the voltage gated sodium ion channels at the next node to open and a new action potential is initiated at the next node. The refractory period stops an action potential forming at the node in the backwards direction. So, myelin sheath is essential for fast impulse transmission.

If there is a low oxygen concentration during foetal development, the myelin sheath can become damaged resulting in cerebral paralysis in the newborn baby. Adults can suffer damage to the myelin sheath if they suffer from multiple sclerosis (MS) – an autoimmune condition that destroys the myelin sheath. In the elderly, vascular dementia can occur if there is reduced blood flow in the brain that harms the myelin sheath.

The research team investigated to see if the mutation could protect myelin. They used new-born mice and exposed them to low oxygen conditions for a week. The mice that had the mutation did better in tests that measured their performance in learning, memory and social behaviour. Further tests showed that these mice had more myelin in their myelin sheaths.

The next phase of the project examined if the mutation could help repair the damage that is seen in MS. The mice with the mutation regenerated more myelin and faster. There was also evidence of more cells that produce myelin. Chemical analysis showed that the mice had higher concentrations of ATDR (made from vitamin A) in their brains and the mutation was increasing the activity of enzymes that convert vitamin A into its metabolites. These metabolites helped with the production of the cells that produce myelin. Mice with MS-like symptoms were treated with ATDR and they showed less severe symptoms and better movement.

This research could change how MS is treated. Currently the focus is on reducing the activity of the immune system, which has other side effects. This would be using a more direct approach with fewer side effects. Fingers crossed this is the breakthrough needed.

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