Ottawa scientists show how brain’s electrical insulation gets damaged

Ottawa, ON – In an advanced online publication of Nature, published on December 21, scientists from the Ottawa Health Research Institute (OHRI) show that myelin contains specialized receptors for the neurotransmitter glutamate. They also show the compounds that block this receptor can greatly reduce myelin damage, a discovery that could one day lead to new treatments for MS, stroke, and traumatic brain/spinal cord injuries.

Dr Peter Stys, the senior author, is a senior scientist in the Neuroscience Program at the OHRI, a professor of medicine in the division of neurology at the University of Ottawa and an attending physician at the Ottawa Hospital in the division of neurology.

Dr Stys and Dr Ileana Micu, the lead research associate on the project, suspected that myelin damage involved calcium, but had to invent a new technique to test the hypothesis.

“Living myelin is very difficult to study,” says Dr Micu. “We developed a unique technique using state-of-the-art laser scanning microscopes that allows researchers for the first time ever, to measure changes in calcium levels in the tiny spaces within the myelin spirals. We used oxygen deprivation to damage isolated nerve fibres and we found that indeed, calcium levels do go up in myelin. But the big surprise was when we found that a compound known to block a receptor for glutamate could block this calcium increase and greatly reduce myelin damage.”

This specialized glutamate receptor, called the NMDA (N-methyl-D-aspartate) receptor, has been known to exist in other parts of the brain for 30 years but this is the first time it has been detected in myelin. In conditions such as stroke, neurons are known to release glutamate, but in immune disorders such as MS, Dr Stys suspects that glutamate coming from inflammatory cells might be directly injuring myelin.

Dr Stephen G Waxman, the Bridget Flaherty professor and chairman of neurology at Yale University School of Medicine has studied myelin for many years and thinks this discovery may be a key step in the fight against MS.

“Although we have known for many decades that myelin, and the oligodendrocytes that produce it in the brain and spinal cord, are injured in MS, the details of how this injury occurs – what molecules are involved, how they interact, and how this injures the myelin – have not been understood,” says Dr Waxman. “This latest work by Stys and his coworkers provides an important and novel insight about this, and identifies a new molecule which could become a ‘molecular target’ as we search for new and more effective therapies for MS.”

Myelin, together with the nerve fibres it envelopes and associated supporting cells, is also referred to as “white matter” because a high fat content makes it much paler than the more well known “grey matter” in the brain.