The insulating myelin sheath enwrapping the cable-like axons of nerve cells is the major target of attack of the immune system in multiple sclerosis. Such attack causes neural short-circuits that give rise to the muscle weakness, loss of coordination, and speech and visual loss in the disease.
Now, Douglas Fields of the National Institute of Child Health and Human Development and his colleagues have reported in Neuron that supporting cells called astrocytes in the central nervous system (CNS) promote myelination by releasing an immune system molecule that triggers myelin-forming cells to action. The finding, they say, "may offer new approaches to treating demyelinating diseases."
Astrocytes, so named because of their star-like shape, are the most prominent supporting cells in the nervous system. They provide critical regulatory molecules that enable nerve cells to develop and connect properly.
In their studies, Fields and his colleagues sought to understand other research findings indicating that the electrical activity of nerve cells somehow triggers myelin-producing cells, called oligodendrocytes, to form the myelin membrane surrounding the nerve cells.
In their studies, the researchers cultured rat and mice neurons together with oligodendrocytes and conducted experiments to understand the mechanism of myelin formation. They found that electrical stimulation of the neurons caused production of the energy molecule ATP, and this ATP increases myelination.
Drawing on other researchers' findings that an immune signaling molecule called leukemia inhibitory factor (LIF) might be involved, they explored whether LIF was a key molecule in the ATP-triggered myelination machinery. Their experiments revealed LIF's central role in the machinery, and further studies showed that astrocytes were the source of that LIF.
Indeed, when they tested directly whether astrocytes were important in promoting myelination in the cell cultures, they found the cells to be potent promoters of the process.
"Taken together, these results reveal a new mechanism by which electrical activity promotes myelination of CNS axons at a later developmental stage and possibly into postnatal life," concluded the researcher. They wrote that the "new findings may provide novel approaches to understanding and treating myelin disorders in the CNS" after the immature oligodendrocytes have matured into myelinating cells.
The researchers include Tomoko Ishibashi, Kelly A. Dakin, Beth Stevens, Philip R. Lee, and R. Douglas Fields of the National Institute of Child Health and Human Development in Bethesda, MD; Serguei V. Kozlov and Colin L. Stewart of the National Cancer Institute in Bethesda, MD. This work was supported by the intramural research program at National Institutes of Health, National Institute of Child Health and Human Development.
Reference: Ishibashi et al.: "Astrocytes Promote Myelination in Response to Electrical Impulses." Publishing in Neuron 49, 823-832, March 16, 2006. DOI 10.1016/j.neuron.2006.02.006
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