March 16, 2006
Electrical impulses foster myelination, the insulation process that speeds communication among brain cells, report researchers at two institutes of the National Institutes of Health.
"This finding provides important information that may lead to a greater understanding of disorders such as multiple sclerosis that affect myelin, as well as a greater understanding of the learning process," said Duane Alexander, M.D., Director of the NICHD.
The study appears in the March 16 Neuron and was conducted by researchers at the National Institute of Child Health and Human Development and the National Cancer Institute.
Neurons—specialized cells of the brain and nervous system—communicate via a relay system of electrical impulses and specialized molecules called neurotransmitters, explained the study's senior author, R. Douglas Fields, Ph.D., Head of NICHD's Nervous System Development and Plasticity Section.
A neuron generates an electrical impulse, causing the cell to release its neurotransmitters, he said. The neurotransmitters, in turn, bind to nearby neurons. The recipient neurons then generate their own electrical impulses and release their own neurotransmitters, triggering the process in still more neurons, and so on.
Neurons conduct electrical impulses more efficiently if they are covered with an insulating material known as myelin, Dr. Fields added. Layers of myelin are wrapped around the fiber-like projections of neurons like electrical tape wrapped spiral-fashion around an electrical cable. Human beings are born with comparatively little myelin, and neurons become coated with the material as they develop. Moreover, mental activity appears to influence myelination, Dr Fields said. For example, neglected children have less myelin in certain brain regions than do other children.
However, raising animals in stimulating environments increases their myelin production. Also, mastering an activity, such as learning to play the piano, fosters myelination, and myelin is decreased in several mental disorders, including schizophrenia and bipolar disorder.
Dr Fields said that these phenomena implied that the cells forming myelin must somehow sense electrical impulse activity in neurons and regulate myelination accordingly.
To conduct their study, Dr. Fields and his coworkers isolated neurons from mouse brains and grew them in laboratory cultures with two other kinds of brain cells, oligodendrocytes and astrocytes. Previous studies had determined that oligodendrocytes deposit myelin on neurons, but how electrical impulse activity might stimulate them to do so was unknown.
In their laboratory cultures, the researchers stimulated the neurons by passing an electrical current through them. This electrical stimulation was designed to mimic the normal activity that takes place in the brain when neurons communicate with each other.
The researchers found that the electrical stimulation caused the neurons to release adenosine triphosphate (ATP), a high-energy molecule essential to many biological processes. In this instance, however, the ATP bound to special sites, or receptors, on the surface of the astrocytes, causing them to release a substance known as leukemia inhibitory factor (LIF). LIF, in turn, bound to the oligodendrocytes, stimulating those cells to deposit myelin around the neurons.
Dr. Fields explained that the finding has implications for disorders affecting myelination, such as Alexander disease, which is a fatal neurological disorder of childhood caused by a genetic defect in astrocytes. The brains of children who have Alexander disease also have severe myelin defects. The finding that astrocytes indirectly relay signals from neurons to oligodendrocytes provides a possible explanation for the lack of myelin characteristic of the disorder. Researchers may be able to provide treatment for demylinating diseases, such as multiple sclerosis, by developing drugs that mimic the actions of ATP and LIF on their target cells. Similarly, an understanding of how myelination takes place may offer insight into the learning process.
Other authors of the study are: Tomoko Ishibashi, Kelly A. Dakin, Beth Stevens and Philip R. Lee, of the NICHD; and Serguei V. Kozlov and Colin L. Stewart of the NCI.
The NICHD sponsors research on development, before and after birth; maternal, child, and family health; reproductive biology and population issues; and medical rehabilitation. For more information, visit the Web site at http://www.nichd.nih.gov/.
The National Institutes of Health (NIH) — The Nation's Medical Research Agency — includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit http://www.nih.gov.