Schwann cells are surrounded by sheets of tissue known as basal lamina. The outside of the basal lamina is covered in a layer of connective tissues known as the endoneurium. The endoneurium contains blood vessels, macrophages, and fibroblasts. Finally, the inner surface area of the lamina layer faces the plasma membrane of the Schwann cells. For the myelin sheath to be created by Schwann cells in the PNS, the plasma membrane of these cells needs to wrap itself around the axons of the neuron concentrically, spiralling to add membrane layers.
This plasma membrane contains high levels of fat which is essential for the construction of myelin sheath. Sometimes, as many as revolutions of Schwann cell spirals around the axons of the neurons. Within the CNS, oligodendrocytes are the glia cells which also create myelin sheath. Oligodendrocytes are star-shaped cells which have about 15 arms coming out of their cell body, meaning it is able to myelinate multiple axons at one time.
In a similar fashion to Schwann cells, oligodendrocytes spiral around the axons of neurons to form a myelin sheath. The cell body and the nucleus of the oligodendrocytes, however, remain separate from the sheath and so do not wrap around the axon, unlike Schwann cells. The oligodendrocytes repeatedly spiral around the axon to form a lipid-rich membrane, thus functioning similarly to Schwann cells.
One oligodendrocyte can myelinate multiple axons at once in a coordinated process and simultaneously. The onset of myelination is often triggered by neuronal activity in the CNS. This was proven in studies of rats, some of which were grown in the dark and some in the light.
It was found that the optic nerves of the rate who grew up in the dark had fewer developed myelinated axons than the optic nerves of those who did not grow up in the dark.
Overall, it has been found that the degree of myelination depends on the amount of neuronal activity, with increased neuronal activity increasing the amount of myelination. Myelination first occurs during embryonic development and is then a continuous process from birth, maturing at about 2 years of age. Once at this stage, motor and sensory systems are matured and cerebral myelination is mostly complete.
However, some processes are myelinated later in life, with some connections between the thalamus and prefrontal cortex maturing between the ages of 5 and 7 years of age. Similarly, myelination of connections between association areas of the cerebral cortex continues into the 20s and 30s of individuals. Typically, myelination within the brainstem and cerebellum will mature first followed by maturation of myelination in the lobes of the cerebral cortex.
Most individuals between the ages of 20 and 29 years of age will be at their peak for their ability to perform physically due to myelination being matured in relevant areas. However, myelination continues to develop throughout adulthood in regions responsible for integrating information for purposeful action such as in association areas, finally peaking at around 50 years of age.
Although there is continued myelination in association areas, the nervous system begins to decline in general from the age of 20, with the thinning of the cortex and the number of oligodendrocytes decreasing. Issues with myelination could be the result of damage, infections, trauma, genetic mutations, and autoimmune diseases. If myelin sheath on the axons is damaged or not able to be formed, this can result in electrical signals traveling down the axons to be slower or disrupted.
The myelin sheath is crucial for the normal operation of the neurons within the nervous system: the loss of the insulation it provides can be detrimental to normal function. Ultimately, this could impair the myelination process and the functions of the Schwann cells and oligodendrocytes which could eventually lead to neurodegeneration. Depending on the extent of the issue and the condition experienced, an individual with myelination problems may be experiencing one or more of the following symptoms:.
The process of myelin being destroyed or not functioning properly is called demyelination. Diseases associated with demyelination can range from acute to chronic. This can result in weakness, numbness, and may eventually cause paralysis, making it a life-threatening condition.
As this condition causes damage to the axons of neurons, it can lead to electrical conduction being blocked. Multiple sclerosis MS is another demyelinating condition which affects the myelin sheath. This is a disease which causes the immune system of individuals to attack the CNS, meaning the myelin sheath will be damaged.
MS can weaken muscles, damage coordination, and can cause paralysis in the worst conditions. This condition therefore makes it difficult for electrical signals to be conducted through the neurons, resulting in compromised communication between neurons.
Finally, peripheral nerve tumors, such as Schwannomas are conditions that affect the Schwann cells that produce myelin sheath. A schwannoma is a tumor that is usually benign but in rare instances can be harmful and cancerous. Although these are rarely harmful, they can result in nerve damage and a loss of motor control.
As these tumors affect the cells which produce myelin sheath in the PNS, this can negatively affect how the axons conduct electrical impulses, resulting in symptoms such as muscle weakness, numbness, and some pain. Olivia has been working as a support worker for adults with learning disabilities in Bristol for the last four years. Guy-Evans, O. Myelin sheath. Simply Psychology. Cech, D. Elsevier Health Sciences.
Moore, S. A role of oligodendrocytes in information processing. Nature communications, 11 1 , Kirkwood, C. Although there are several molecular or morphological differences between nerve fibers in the PNS and CNS, the basic myelin sheath arrangement and the electrophysiological characteristics are essentially the same.
Are all axons covered with myelin? No; they can be either myelinated or unmyelinated. Myelinated axons are ensheathed along their entire length. 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. 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 , — Poliak, S. The local differentiation of myelinated axons at nodes of Ranvier.
Nature Reviews Neuroscience 4 , — Sherman, D. Mechanisms of axon ensheathment and myelin growth. Nature Reviews Neuroscience 6 , — Siffrin, V. Multiple sclerosis — candidate mechanisms underlying CNS atrophy. Trends in Neurosciences 33 , — Susuki, K. Molecular mechanisms of node of Ranvier formation. Current Opinion in Cell Biology 20 , —
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