The gaps in the middle of the fibers are called nodes, which help transmit electrical signals in neurons. Desmazieres, et al. Journal of Neuroscience, In this illustration of a neuron, myelin is shown in yellow. In the nerves outside of the brain and spinal cord, myelin is produced by support cells called Schwann cells. The nuclei of the Schwann cells are shown here in pink.
This image shows a cross-section of a mouse nerve. Myelin, labelled in red, can be seen surrounding the individual nerve cell projections in blue. Sherman et al. The Journal of Neuroscience, About the Author. A quantitative measure of myelination development in infants, using MR images. Mapping infant brain myelination with magnetic resonance imaging.
Journal of Neuroscience. Gasser HS, Grundfest H. Axon diameters in relation to the spike dimensions and the conduction velocity in mammalian fibers. American Journal of Physiology. Giedd JN. Structural magnetic resonance imaging of the adolescent brain.
Annals of the New York Academy of Sciences. Huxley AF, Stampfli R. Evidence for saltatory conduction in peripheral myelinated nerve fibres. Journal of Physiology. Nature Communications. Prolonged myelination in human neocortical evolution. Proceedings of the National Academy of Sciences. Characterization of cloned cDNA representing rat myelin basic protein: absence of expression in brain of shiverer mutant mice.
Rushton WAH. A theory of the effects of fibre size in medullated nerve. The restoration of conduction by central remyelination. Tasaki I. The electro-saltatory transmission of the nerve impulse and the effect of narcosis upon the nerve fiber.
Waxman SG. In contrast, transgenic mice that overexpress neuregulin 1 become hypermyelinated. Although several reports show that oligodendrocytes respond to neuregulin 1 in vitro, analyses of a series of conditional null mutant animals lacking neuregulin 1 showed normal myelination Brinkmann et al. It is still unclear how myelination is regulated in the CNS. How does myelin enhance the speed of action potential propagation? It insulates the axon and assembles specialized molecular structure at the nodes of Ranvier.
In unmyelinated axons, the action potential travels continuously along the axons. For example, in unmyelinated C fibers that conduct pain or temperature 0. In contrast, among the myelinated nerve fibers, axons are mostly covered by myelin sheaths, and transmembrane currents can only occur at the nodes of Ranvier where the axonal membrane is exposed. At nodes, voltage-gated sodium channels are highly accumulated and are responsible for the generation of action potentials.
The myelin helps assemble this nodal molecular organization. For example, during the development of PNS myelinated nerve fibers, a molecule called gliomedin is secreted from myelinating Schwann cells then incorporated into the extracellular matrix surrounding nodes, where it promotes assembly of nodal axonal molecules. Due to the presence of the insulating myelin sheath at internodes and voltage-gated sodium channels at nodes, the action potential in myelinated nerve fibers jumps from one node to the next.
This mode of travel by the action potential is called "saltatory conduction" and allows for rapid impulse propagation Figure 1A. Following demyelination, a demyelinated axon has two possible fates. The normal response to demyelination, at least in most experimental models, is spontaneous remyelination involving the generation of new oligodendrocytes. In some circumstances, remyelination fails, leaving the axons and even the entire neuron vulnerable to degeneration.
Remyelination in the CNS: from biology to therapy. Nature Reviews Neuroscience 9, — All rights reserved. Figure Detail What happens if myelin is damaged?
The importance of myelin is underscored by the presence of various diseases in which the primary problem is defective myelination. Demyelination is the condition in which preexisting myelin sheaths are damaged and subsequently lost, and it is one of the leading causes of neurological disease Figure 2.
Primary demyelination can be induced by several mechanisms, including inflammatory or metabolic causes. Myelin defects also occur by genetic abnormalities that affect glial cells. Regardless of its cause, myelin loss causes remarkable nerve dysfunction because nerve conduction can be slowed or blocked, resulting in the damaged information networks between the brain and the body or within the brain itself Figure 3.
Following demyelination, the naked axon can be re-covered by new myelin. This process is called remyelination and is associated with functional recovery Franklin and ffrench-Constant The myelin sheaths generated during remyelination are typically thinner and shorter than those generated during developmental myelination.
In some circumstances, however, remyelination fails, leaving axons and even the entire neuron vulnerable to degeneration. Thus, patients with demyelinating diseases suffer from various neurological symptoms. The representative demyelinating disease , and perhaps the most well known, is multiple sclerosis MS.
This autoimmune neurological disorder is caused by the spreading of demyelinating CNS lesions in the entire brain and over time Siffrin et al. Patients with MS develop various symptoms, including visual loss, cognitive dysfunction, motor weakness, and pain.
Approximately 80 percent of patients experience relapse and remitting episodes of neurologic deficits in the early phase of the disease relapse-remitting MS. There are no clinical deteriorations between two episodes. Approximately ten years after disease onset, about one-half of MS patients suffer from progressive neurological deterioration secondary progressive MS.
About 10—15 percent of patients never experience relapsing-remitting episodes; their neurological status deteriorates continuously without any improvement primary progressive MS. Importantly, the loss of axons and their neurons is a major factor determining long-term disability in patients, although the primary cause of the disease is demyelination. Several immunodulative therapies are in use to prevent new attacks; however, there is no known cure for MS. Figure 3 Despite the severe outcome and considerable effect of demyelinating diseases on patients' lives and society, little is known about the mechanism by which myelin is disrupted, how axons degenerate after demyelination, or how remyelination can be facilitated.
To establish new treatments for demyelinating diseases, a better understanding of myelin biology and pathology is absolutely required. How do we structure a research effort to elucidate the mechanisms involved in developmental myelination and demyelinating diseases? We need to develop useful models to test drugs or to modify molecular expression in glial cells. One strong strategy is to use a culture system. Coculture of dorsal root ganglion neurons and Schwann cells can promote efficient myelin formation in vitro Figure 1E.
Researchers can modify the molecular expression in Schwann cells, neurons, or both by various methods, including drugs, enzymes, and introducing genes , and can observe the consequences in the culture dish.
Modeling demyelinating disease in laboratory animals is commonly accomplished by treatment with toxins injurious to glial cells such as lysolecithin or cuprizone. Autoimmune diseases such as MS or autoimmune neuropathies can be reproduced by sensitizing animals with myelin proteins or lipids Figure 3. Some mutant animals with defects in myelin proteins and lipids have been discovered or generated, providing useful disease models for hereditary demyelinating disorders.
Further research is required to understand myelin biology and pathology in detail and to establish new treatment strategies for demyelinating neurological disorders.
Myelin can greatly increase the speed of electrical impulses in neurons because it insulates the axon and assembles voltage-gated sodium channel clusters at discrete nodes along its length. Myelin damage causes several neurological diseases, such as multiple sclerosis.
Future studies for myelin biology and pathology will provide important clues for establishing new treatments for demyelinating diseases. Brinkmann, B. Neuron 59 , — Franklin, R.
Remyelination in the CNS: From biology to therapy. Nature Reviews Neuroscience 9 , — Nave, K. Axonal regulation of myelination by neuregulin 1.
Current Opinion in Neurobiology 16 , — Scientists have discovered that the body heals some lesions naturally by stimulating oligodendrocytes in the area — or by recruiting young oligodendrocytes from further away — to begin making new myelin at the damaged site. However, this natural repair process is slow and incomplete. Scientists are investigating several different strategies for stimulating the repair of myelin , including testing existing drugs , finding ways to stimulate oligodendrocytes to produce myelin, and ways to protect oligodendrocytes and myelin from further damage.
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