Published October 6, 2015
Researchers at the Hunter James Kelly Research Institute (HJKRI) have discovered a new way to study the interface where cells in the myelination process connect — a method that may lead to a better understanding of myelin diseases.
Interactions between brain cells hold the key to healthy brain function and cognition.
Researchers used a neuron to attract a glial cell, which produces myelin, and examined them in a two-chamber system separated by a membrane.
“When the cells in the upper chamber ‘recognize’ the cells in the bottom chamber, they ‘reach’ through the holes in the membrane for each other and touch. That is the intersection we can isolate and study,” Feltri explained.
Using this technique, the researchers discovered novel proteins at that intersection called prohibitins, which, they found, are necessary for the production of myelin.
First author Yannick Poitelon, PhD, explained glial cells support neurons metabolically and protect axons that can measure up to one meter in length, extending far away from the glial cell.
Poitelon, who is undertaking postdoctoral training at UB, is a postdoctoral research scientist at HJKRI.
Scientists at the HJKRI conduct research to better understand myelin, the fatty insulator that enables communication between nerve cells. The researchers study how damage to myelin occurs, and how that damage may be repaired.
Cellular interactions that trigger the production of myelin are especially hard to pinpoint. The crucial point of contact between two types of cells — the connection between axons, along which nerves impulses travel, and glial cells, which support neurons — is essentially hidden.
“Myelin is made by a glial cell wrapping around an axon cell,” explained Feltri, senior author on the paper.
“To study myelin, you really need to study both cells. The glial cell wraps like a spiral around the axon, so every time you try to study the region of contact between the two cells, you end up studying the whole combination. It's very hard to just look at the interface, which is critical in certain diseases,” she said.
“In Krabbe disease for example, the problem is not just that there isn’t sufficient myelin, but that the glial cell is not providing proper support to the neuron. But to figure out exactly what's going wrong, we needed a better way to study that interface,” said Feltri.
“This has profound implications for glial diseases like Krabbe, Charcot-Marie Tooth, peripheral neuropathies or multiple sclerosis, because the dysfunction of glial cells ends up impairing the interactions with neurons, which as a result suffer and degenerate causing devastating clinical symptoms,” said Poitelon.
“Similarly, neurodegenerative diseases like Huntington's or Lou Gehrig's disease, that were considered uniquely diseases of neurons in the past, are now considered diseases of cellular communications between neurons and glial cells,” he said.
In addition to improving the understanding of and development of new treatments for myelin diseases, the discovery will also make it easier to study all kinds of cellular interactions, not just those in the brain.
“Using this method, we can isolate the portion of a cell that comes into contact with another cell, and analyze all the proteins that are present only in this subcellular fraction,” Feltri explained.
Other HJKRI co-authors include:
Benita S. Katzenellenbogen, PhD, of the University of Illinois, and A. Sannino, of the University of Salento, also co-authored.
Other collaborators are S. Bogni, V. Matafora, A. Bachi and C. Taveggia — all of San Raffaele Hospital.
The work was funded by the National Institutes of Health.
The HJKRI, part of UB’s New York State Center of Excellence in Bioinformatics and Life Sciences, was established in 1997 by Buffalo Bills Hall of Fame quarterback Jim Kelly and his wife Jill.
It was named after their infant son Hunter, who was diagnosed with Krabbe Leukodytrophy, an inherited fatal disorder. He died in 2005 at the age of 8.