By:Keiichiro Susuki, M.D., Ph.D.(Dept. That Neuroscience, Baylor university of Medicine)© Education
Citation:Susuki,K.(2010)Myelin: A committed Membrane for Cell Education3(9):59





How does our nervous mechanism operate therefore quickly and efficiently? The prize lies in a membranous structure called myelin.

You are watching: The nodes of ranvier are found only on myelinated, peripheral neuron processes.

All our tasks — eating, walking, talk — are controlled by our brains, the facility of the nervous system. The brain receives substantial amounts of details from outside our body via our five senses (vision, sound, taste, touch, and smell), integrates this information, and also orders our muscles to take it action. Just how is all that completed so efficiently? The answer lies in a membrane structure dubbed myelin.

All details both to and from the body must be coordinated and transmitted all at once and an extremely quickly. The mind itself requires extremely fast speeds to run at even at the most basic level. How do the biological tissues of our body support such fast coordination of the brain, limbs, and also sensory input? They execute so with nervous mechanism tissue that imitates electrical wiring.

The nervous mechanism is consisted of of two primary cell types: neurons and glial cells. This cells interact with each various other to perform important tasks in the worried system. The glial cells support neurons structurally and also maintain their irreversible neuronal integrity, and neurons regulate glial cabinet behavior. In this support of neurons, glial cells have end up being highly specialized. Glial cells, which can be separated into several types, have actually various essential functions, together as giving structural support, expansion support, and also insulation about the axon.

Why must glial cells assistance neurons? Neurons are devoted cells the receive and also send signal to other cells through fragile and thin to move extensions dubbed axons. This axons prolong over distances long and short to reach their target, ultimately connecting neurons with various other nerve tissue, muscle tissue, or sensory organs (Figure 1A). Because that example, part motor neurons in the spinal cord have actually axons the exceed 1 m in length, connecting the spine to the reduced limb muscles. This axons transmit signals to the target muscle in the kind of electric impulses called action potentials. However, the axons alone are not enough to develop rapid conduction that the electric existing necessary because that this signal to be sent. Glial cells are the crucial element for supporting the message neurons send and also receive almost everywhere the body. Lot like the insulation approximately the wires in electrical systems, glial cells form a membraneous sheath neighboring axons called myelin, thereby insulating the axon. This myelination, as it is called, can significantly increase the rate of signals transmitted between neurons (known as action potentials). Indeed, the development of myelin allowed vertebrates to achieve efficient concerned systems in spite of their huge body size.

What precisely is myelin? Myelin is a concentrically laminated membrane structure surrounding an axon about which lamellae (or moving protrusions) repeat radially in ~ a period of around 12 nm (Waxman, Kocsis & Stys 1995; Sherman & Brophy 2005). The myelin lamella is formed by fusion of the apposed inner leaflets the the plasma membrane in glial cells, with no intervening cytoplasm (Figure 1B).

Depending top top the location, different glial cell types make myelin in a different manner. Schwann cells make myelin in the peripheral nervous system (PNS: nerves) and also oligodendrocytes in the central nervous system (CNS: brain and spinal cord). In the PNS, one Schwann cell develops a solitary myelin sheath (Figure 1A). Through contrast, in the CNS, the oligodendrocyte sends cell processes to myelinate multiple segments on plenty of axons (Figure 2). Although over there are numerous molecular or morphological differences in between nerve fibers in the PNS and also CNS, the simple myelin sheath arrangement and also the electrophysiological attributes are essentially the same.

Are all axons spanned with myelin? No; they have the right to be one of two people myelinated or unmyelinated. Myelinated axons space ensheathed follow me their entire length. The axon caliber (diameter) in mammalian PNS varieties from 0.1 μm come 20 μm, with unmyelinated axons being less than 2 μm and also myelinated axons being more than 1–2 μm in diameter. In the CNS, virtually all axons with diameters better than 0.2 μm are myelinated. In cross section, the myelinated axon shows up as a practically circular profile surrounded by a spirally wound multilamellar sheath (Figure 1C and D). Amazingly, a big myelinated axon may have actually up come 250 to 300 turns of myelin wrapping about it. The ratio in between axon diameter and also that the the full nerve fiber (axon and also myelin) is 0.6–0.7, a proportion that is well kept regardless of the axon caliber. The size of the myelin sheath along the axon is about 1 mm in the PNS. In between two adjacent myelin segments, over there are approximately 1-μm-long gaps called nodes the Ranvier (Figure 1A and also E). At the nodes, the axon is exposed to the extracellular space.

How is the spiral wrapping of the myelin sheath approximately axons developed precisely and appropriately? One mechanism has actually been determined in PNS myelination. In the PNS, neuregulin 1 type III protein is to express on the axon surface and also interacts v glial ErbB receptors, and also it has actually a pivotal duty for Schwann cabinet differentiation and myelination (for review, watch Nave & Salzer 2006). Unmyelinated autonomic neurons express short levels that neuregulin 1 kind III on the axon surface, whereas greatly myelinated axons refer high levels.

Without neuregulin 1 type III, Schwann cells in culture derived from these mutant mouse cannot myelinate neurons in the spinal cord (dorsal root ganglion neurons). Intriguingly, in usually unmyelinated fibers, compelled expression that neuregulin 1 form III in the postganglionic fibers of sorry neurons get an impressive in culture can be compelled to myelinate. Thus, the level of neuregulin 1 type III ~ above the PNS axons is a vital instructive signal because that myelination. Furthermore, above the threshold, the myelin formation is correlated with the lot of neuregulin 1 kind III presented by the axon to the Schwann cell. Decreased expression of neuregulin 1 type III leads to a diluent than regular myelin sheath in the heterozygous mutant mouse of this molecule. In contrast, transgenic mice that overexpress neuregulin 1 end up being hypermyelinated.

One amazing question is: go neuregulin-ErbB signaling control CNS myelination as well? Although several reports present that oligodendrocytes respond to neuregulin 1 in vitro, analyses of a collection of conditional null mutant pets lacking neuregulin 1 showed normal myelination (Brinkmann et al. 2008). That is tho unclear how myelination is regulated in the CNS.

How does myelin boost the rate of activity potential propagation? the insulates the axon and also assembles devoted molecular structure at the nodes the Ranvier. In unmyelinated axons, the action potential travels continuously along the axons. For example, in unmyelinated C fibers the conduct pains or temperature (0.4–1.2 μm in diameter), conduction velocity along the axon is 0.5–2.0 m/s (as fast as friend walk or jog).

In contrast, amongst the myelinated nerve fibers, axons are mostly covered by myelin sheaths, and also transmembrane currents have the right to only occur at the nodes that Ranvier wherein the axonal membrane is exposed. Myelin is wealthy in lipids (approximately 80%) and also can as such act as an insulator (meaning high transverse resistance and also a low electrical capacitance) follow me the internodal segments. Because that example, conduction velocity in the most thoroughly myelinated axons (12–20 μm in diameter) is 70–120 m/s (race car speed), although other components such as axon caliber deserve to influence this velocity.

At nodes, voltage-gated sodium channels are highly collected and are responsible because that the generation of activity potentials. Come induce and also maintain nodal sodium channel clusters, specific molecules are also enriched in ~ nodal axons, including cell adhesion molecule such together neurofascin 186 and cytoskeletal and scaffolding proteins such as bIV spectrin (Poliak & Peles 2003; Susuki & Rasband 2008). The myelin helps assemble this nodal molecule organization. For example, during the development of PNS myelinated nerve fibers, a molecule called gliomedin is secreted from myelinating Schwann cell then incorporated into the extracellular matrix neighboring nodes, where it promotes assembly the nodal axonal molecules. Because of the visibility of the insulating myelin sheath at internodes and voltage-gated sodium networks at nodes, the action potential in myelinated nerve yarn jumps native one node to the next. This mode of travel by the activity potential is called "saltatory conduction" and enables for rapid impulse propagation (Figure 1A).

The case in the CNS is illustrated. Adhering to demyelination, a demyelinated axon has two possible fates. The normal solution to demyelination, at the very least in most speculative models, is voluntarily remyelination entailing the generation of brand-new oligodendrocytes. In some circumstances, remyelination fails, leaving the axons and even the whole neuron delicate to degeneration.
© 2008 Publishing team Franklink, R. J. M. & ffrench-Constant, C. Remyelination in the CNS: from biology come therapy. evaluate Neuroscience 9, 839–855 (2008). All civil liberties reserved.

What happens if myelin is damaged? The importance of myelin is underscored by the presence of various conditions in i m sorry the primary difficulty is defective myelination. Demyelination is the problem in i beg your pardon preexisting myelin sheaths room damaged and subsequently lost, and it is one of the leading reasons of neurological disease (Figure 2). Primary demyelination have the right to be induced by number of mechanisms, including inflammatory or metabolic causes. Myelin defects additionally occur by hereditary abnormalities that affect glial cells. Regardless of the cause, myelin loss causes remarkable nerve dysfunction since nerve conduction deserve to be slowed or blocked, resulting in the damaged information networks between the brain and the body or in ~ the brain itself (Figure 3).

Following demyelination, the naked axon can be re-covered by new myelin. This process is referred to as remyelination and also is linked with practical recovery (Franklin and also ffrench-Constant 2008). The myelin sheaths generated throughout remyelination are frequently thinner and much shorter than those generated throughout developmental myelination. In some circumstances, however, remyelination fails, leaving axons and also even the whole neuron breakable to degeneration. Thus, patients through demyelinating conditions suffer from various neurological symptoms.

The representative demyelinating disease, and also perhaps the most well known, is lot of sclerosis (MS). This autoimmune neurological disorder is resulted in by the dispersing of demyelinating CNS lesions in the entire brain and over time (Siffrin et al. 2010). Patients through MS develop various symptoms, including visual loss, cognitive dysfunction, motor weakness, and pain. Around 80 percent the patients experience relapse and also remitting illustration of neurologic deficits in the beforehand phase that the an illness (relapse-remitting MS). There are no clinical deteriorations between two episodes. Roughly ten year after condition onset, around one-half of multiple sclerosis patients suffer from steady neurological deterioration (secondary steady MS). Around 10–15 percent that patients never ever experience relapsing-remitting episodes; your neurological status deteriorates continuously without any development (primary steady MS). Importantly, the lose of axons and also their neurons is a significant factor identify long-term disability in patients, although the primary cause of the an illness is demyelination. Numerous immunodulative therapies room in use to prevent new attacks; however, over there is no well-known cure for MS.

Despite the serious outcome and also considerable impact of demyelinating diseases on patients" lives and society, little is known around the mechanism through which myelin is disrupted, exactly how axons degenerate after demyelination, or exactly how remyelination have the right to be facilitated. To establish new treatments because that demyelinating diseases, a better understanding that myelin biology and pathology is absolutely required.

How carry out we structure a research effort to elucidate the mechanisms connected in developmental myelination and demyelinating diseases? We have to develop advantageous models to test drugs or to change molecular expression in glial cells. One strong strategy is to usage a society system. Coculture the dorsal source ganglion neurons and Schwann cells deserve to promote efficient myelin formation in vitro (Figure 1E). Researchers can modify the molecule expression in Schwann cells, neurons, or both by miscellaneous methods, consisting of drugs, enzymes, and introducing genes, and also can watch the aftermath in the culture dish.

Modeling demyelinating disease in laboratory pets is commonly accomplished by treatment through toxins injurious to glial cell such as lysolecithin or cuprizone. Autoimmune diseases such together MS or autoimmune neuropathies have the right to be reproduced through sensitizing pets with myelin protein or lipids (Figure 3). Part mutant pets with defects in myelin proteins and lipids have been discovered or generated, providing useful disease models for hereditary demyelinating disorders. Additional research is required to understand myelin biology and also pathology in detail and also to establish new treatment tactics for demyelinating neurological disorders.

Myelin can substantially increase the rate of electrical impulses in neurons due to the fact that it insulates the axon and assembles voltage-gated sodium channel swarm at discrete nodes follow me its length. Myelin damage reasons several neurological diseases, such as multiple sclerosis. Future researches for myelin biology and also pathology will carry out important hints for establishing new treatments for demyelinating diseases.

Brinkmann, B. G. Et al. Neuregulin-1/ErbB signaling serves distinct functions in myelination that the peripheral and central nervous system. Neuron 59, 581–595 (2008).

Franklin, R. J. & ffrench-Constant, C. Remyelination in the CNS: from biology come therapy. evaluate Neuroscience 9, 839–855 (2008).

Nave, K. A. & Salzer, J. L. Axonal regulation that myelination through neuregulin 1. Current Opinion in Neurobiology 16, 492–500 (2006).

Poliak, S. & Peles, E. The neighborhood differentiation that myelinated axons in ~ nodes the Ranvier. evaluate Neuroscience 4, 968–980 (2003).

Sherman, D. L. & Brophy, P. J. Mechanisms of axon ensheathment and also myelin growth. evaluate Neuroscience 6, 683–690 (2005).

Siffrin, V. Et al. Lot of sclerosis — candidate mechanisms underlying CNS atrophy. Fads in Neurosciences 33, 202–210 (2010).

Susuki, K. & Rasband, M. N. Molecular mechanisms of node of Ranvier formation. Current Opinion in cabinet Biology 20, 616–623 (2008).

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Waxman, S. G., Kocsis, J. D. & Stys, P. K., eds. The Axon: Structure, function and Pathophysiology. New York: Oxford university Press, 1995.