Myelin, the fatty sheath that surrounds nerve fibres in the brain, is the main target of
multiple sclerosis (MS), but how it becomes damaged has remained a mystery for
decades. Now, in an advanced online publication of Nature (December 21) scientists
from the Ottawa Health Research Institute (OHRI) may have solved the puzzle. They
show for the first time ever that myelin contains specialized receptors for the
neurotransmitter glutamate. And they show that compounds that block this receptor can
greatly reduce myelin damage. This discovery could one day lead to new treatments for
MS, stroke, and traumatic brain and spinal cord injuries.
“Myelin is like the plastic coating that insulates a copper wire,” said Dr. Peter Stys, the
senior author. “Our brains send electrical signals using nerve fibres instead of copper
wires and myelin is the fatty sheath that insulates and protects those fibres.” Dr. Stys 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 they had to invent a new technique to test the
“Living myelin is very difficult to study,” said 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 thirty 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,” said 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. Dr. Antoine Hakim, Director of the
Neuroscience Program at the OHRI says this work puts white matter in a new light.
“This is important research,” said Dr. Hakim. “It puts myelin on par with other targets for
future therapy, and the work will result in a significant re-evaluation of our approach to a
number of diseases that involve white matter injury.”
The work was funded by the National Institute of Neurological Disorders and Stroke
(NINDS), the Canadian Institutes of Heath Research (CIHR), the Heart and Stroke
Foundation of Ontario (HSFO) Centre for Stroke Recovery, an HSFO Career Investigator
Award, the Canadian Institute for Photonic Innovations, and the generosity of private
donors from the local community.
The Ottawa Health Research Institute (OHRI) is the research arm of The Ottawa Hospital
and a major part of the University of Ottawa Faculties of Medicine and Health Sciences.
Ottawa Health Research Institute
613-798-5555 extension 19691
www.ohri.caSubmitted 1/4/2006 10:30:23 PM