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More details can be found in our Privacy Policy. The axon caliber diameter in mammalian PNS ranges from 0. In the CNS, almost all axons with diameters greater than 0. In cross section, the myelinated axon appears as a nearly circular profile surrounded by a spirally wound multilamellar sheath Figure 1C and D. Amazingly, a large myelinated axon may have up to to turns of myelin wrapping around it. The ratio between axon diameter and that of the total nerve fiber axon and myelin is 0.
The length of the myelin sheath along the axon is approximately 1 mm in the PNS. At the nodes, the axon is exposed to the extracellular space.
How is the spiral wrapping of the myelin sheath around axons formed precisely and appropriately? One mechanism has been identified in PNS myelination. Unmyelinated autonomic neurons express low levels of neuregulin 1 type III on the axon surface, whereas heavily myelinated axons express high levels. Without neuregulin 1 type III, Schwann cells in culture derived from these mutant mice cannot myelinate neurons in the spinal cord dorsal root ganglion neurons.
Intriguingly, in normally unmyelinated fibers, forced expression of neuregulin 1 type III in the postganglionic fibers of sympathetic neurons grown in culture can be forced to myelinate. Furthermore, above the threshold, the myelin formation is correlated with the amount of neuregulin 1 type III presented by the axon to the Schwann cell.
Reduced expression of neuregulin 1 type III leads to a thinner than normal myelin sheath in the heterozygous mutant mice of this molecule. 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.
Myelin is a fatty substance that wraps around nerve fibers and serves to increase the speed of electrical communication between neurons. While the function of myelin remained elusive for many years, today scientists are putting their knowledge about this insulating substance to use and investigating strategies to protect and repair myelin in diseases where it is compromised like multiple sclerosis.
Communication between neurons depends on the spread of electrical signals , and, just as wires need to be insulated, so too do neurons. Myelin was discovered in the mids, but nearly half a century passed before scientists discovered its vital role as an insulator. In the midth century, scientists peering into light microscopes noticed something strange about the nerve fibers axons branching from the spinal cord : they were surrounded by a glistening, white, fatty substance.
At the time he thought that myelin was present inside of the nerve fiber and incorrectly likened the substance to bone marrow.
Made of lipids and proteins, myelin was later found to wrap around the axons of neurons. Myelin is made by two different types of support cells. In the central nervous system CNS — the brain and spinal cord — cells called oligodendrocytes wrap their branch-like extensions around axons to create a myelin sheath.
In the nerves outside of the spinal cord, Schwann cells produce myelin. Regardless of where it is in the nervous system, all myelin performs the same function, enabling efficient transmission of electrical signals. Even the best insulation would have trouble maintaining electrical signals over long distances, and axons in large animals like giraffes can be up to 15 feet long. Research through the s showed how myelin ensures that the signal is maintained and transmitted.
In the s, French physician Louis-Antoine Ranvier noted that the myelin sheath is discontinuous, covering most of the nerve fiber but with gaps at regular intervals along the axon. In the s and s, scientists found that this passage of ions helps maintain the electrical signal, allowing it to travel quickly down an axon. In the s, researchers used animal models to assess how electrical nerve signals are altered after axons were stripped of the myelin demyelinated.
When researchers chemically induced myelin loss in the spinal cords of cats, they found that signals moved more slowly along the nerve fiber and often failed to make it to the end of the axon. Around the same time, scientists also made breakthroughs in identifying many of the components of myelin, like the major protein elements of the myelin sheath and the genes that encode them.
Researchers developed mouse models that had defective myelin proteins, resulting in a myelin deficiency. Loss of myelin is a problem for many CNS disorders, including stroke, spinal cord injury, and, most notably, multiple sclerosis MS. MS is a chronic, disabling disease of the CNS that affects more than 2. MS results from the accumulation of damage to myelin and the underlying nerve fibers it insulates and protects. Current research indicates that MS involves an autoimmune response.
Scientists think that immune cells, which normally defend the body against bacteria and viruses, mistakenly attack the myelin sheath, stripping it away and exposing the nerve fibers underneath. In addition, recent research suggests that axon damage occurs early on in the course of the disease. This process continues through adulthood. In a healthy person, nerve cells send impulses to each other along a thin fiber that's attached to the nerve cell body.
These thin projections are called axons and most of them are protected by the myelin sheath, which allows nerve impulses to travel rapidly and effectively. Myelin is vital to a healthy nervous system, affecting everything from movement to cognition.
Repeated attacks eventually lead to scarring. When myelin is scarred, nerve impulses cannot be properly transmitted; they either travel too slowly or not at all. Eventually, axons degenerate as a result of the chronic myelin loss, leading to nerve cell death.
Demyelination is the term used to describe the destruction of the myelin sheath, the protective covering surrounding nerve fibers. This damage causes nerve signals to slow down or stop, resulting in neurological impairment.
Depending on where in the central nervous system myelin is attacked, symptoms like sensory disturbances, vision problems, muscle spasms, and bladder problems begin to manifest. This is why the symptoms of MS vary widely from one person to another, as the location of myelin attacks varies within the central nervous system. In addition to the variable sites of immune system attacks in your brain and spinal cord, the timing of these attacks is also unpredictable, though there are potential triggers like stress or the postpartum period.
Other than multiple sclerosis, damage to myelin can be caused by any number of common and uncommon conditions. The causes of these conditions are unknown. Some, like neuromyelitis optica, ADEM, optic neuritis, and transverse myelitis, are believed to be autoimmune , indirectly damaging the myelin sheath as a result of an abnormal immune assault. There are also demyelinating conditions that mainly affect myelin in the peripheral nervous system, including:.
There are also rare genetic disorders in which a breakdown of myelin or a defective myelin sheath can cause permanent neurological damage. Current therapies for multiple sclerosis target your immune system. While they have been found to decrease the number and severity of MS relapses, there's still no cure for MS. But now, experts are examining therapies that target myelin. While current disease-modifying MS therapies focus on how to prevent your immune system from attacking myelin, scientists are looking into how myelin can be repaired once it has been damaged by the immune system.
The hope is that if myelin is repaired, your neurological function may be restored and your MS will stop getting worse—or at least slow down.
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