Published December 14, 2016
Researchers have identified a critical step in myelination after birth that has significance for treating neurodegenerative diseases like multiple sclerosis (MS).
In MS and similar diseases, myelin — the protective coating that neurons need to function — becomes lost or damaged.
The preclinical research, published in the Journal of Neuroscience, concerns oligodendrocytes, the cells that make myelin, and the progenitor cells that are their precursors.
The work involved the study of voltage-operated calcium channels, which are responsible for initiating many physiological functions.
“Our findings show that these calcium channels modulate the maturation of oligodendrocytes in the brain after birth,” says co-author Pablo M. Paez, PhD, assistant professor in the Department of Pharmacology and Toxicology and research scientist with the Hunter James Kelly Research Institute (HJKRI).
“That’s important because it’s possible that the activity of this calcium channel can be manipulated pharmacologically to encourage oligodendrocyte maturation and remyelination after demyelinating episodes in the brain,” he says.
The researchers found that within two weeks after birth, the maturation of oligodendrocytes and myelination will proceed so long as calcium channels are functioning properly. In their experiments, mice from whom these calcium channels were removed had abnormal oligodendrocyte maturation, which prevented normal myelination.
Paez said it appears that in these animals, the inability to develop myelin normally persists into adulthood, suggesting that the expression of voltage-operated calcium channels during the first steps of myelination is essential for the brain’s normal development.
“If we can further enhance our understanding of how these oligodendrocyte precursor cells mature, then it may be possible to stimulate them to replace myelin in diseases like multiple sclerosis,” he says.
“Demyelination — the loss of myelin — impairs the ability of nerve impulses to travel from nerve cell to nerve cell,” Paez explains. “That can lead to deficits in motor, sensory and cognitive function. While remyelination occurs in many multiple sclerosis lesions, this becomes increasingly less effective over time and eventually fails.”
Paez says the results are of particular interest because many therapies are already on the market that target calcium channels for cardiovascular disorders and other diseases.
“The pharmacology of these calcium channel blockers is very well-understood, so an understanding of how they influence myelination could potentially bring us closer to new therapies more rapidly than some other therapeutic possibilities,” notes Lawrence Wrabetz, MD, professor of neurology and biochemistry and director of the HJKRI.
The study, Conditional Deletion of the L-Type Calcium Channel Cav1.2 in Oligodendrocyte Progenitor Cells Affects Postnatal Myelination in Mice, was supported by the National Institute of Neurological Disorders and Stroke and the National Multiple Sclerosis Society.
Most of the work was conducted at the HJKRI. In addition to Paez, co-authors from the HJKRI are:
Scientists at the HJKRI conduct research to better understand how damage to myelin occurs and how that damage may be repaired.
The institute, 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, after their infant son, Hunter, was diagnosed with Krabbe Leukodystrophy, an inherited fatal disorder of the nervous system.
Researchers from the David Geffen School of Medicine at UCLA and the University of Michigan are other co-authors.