The glial cells support neurons structurally and maintain their long-term neuronal integrity, and neurons regulate glial cell behavior. In this support of neurons, glial cells have become highly specialized. Glial cells, which can be divided into several types, have various important functions, such as providing structural support, growth support, and insulation around the axon. Why must glial cells support neurons? Neurons are specialized cells that receive and send signals to other cells through fragile and thin cellular extensions called axons.
These axons extend over distances long and short to reach their target, ultimately connecting neurons with other nerve tissue, muscle tissue, or sensory organs Figure 1A. For example, some motor neurons in the spinal cord have axons that exceed 1 m in length, connecting the spine to the lower limb muscles. These axons transmit signals to the target muscle in the form of electric impulses called action potentials. However, the axons alone are not enough to produce rapid conduction of the electric current necessary for this signal to be sent.
Glial cells are the key element for supporting the messages neurons send and receive all over the body. Much like the insulation around the wires in electrical systems, glial cells form a membraneous sheath surrounding axons called myelin, thereby insulating the axon. This myelination, as it is called, can greatly increase the speed of signals transmitted between neurons known as action potentials.
Indeed, the evolution of myelin allowed vertebrates to achieve efficient nervous systems despite their large body size. What exactly is myelin? The myelin lamella is formed by fusion of the apposed inner leaflets of the plasma membrane in glial cells, with no intervening cytoplasm Figure 1B. Depending on the location, different glial cell types make myelin in a different manner.
Schwann cells make myelin in the peripheral nervous system PNS: nerves and oligodendrocytes in the central nervous system CNS: brain and spinal cord. By contrast, in the CNS, the oligodendrocyte sends cell processes to myelinate multiple segments on many axons Figure 2. 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.
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Enroll in the International Ophthalmologists contest. Residents and Fellows contest rules International Ophthalmologists contest rules. Original article contributed by :. Hema L. All contributors:. Ramkumar, MD , K. David Epley, M. Assigned editor:. Allison R. Myelinated Retinal Nerve Fiber Layer. ICD - ICD - 9. Zur pathologischen anatomic der netzaut und des scherven. Virchows Arch Pathol Anat. Journal of the American Medical Association. Myelinated retinal nerve fibers: prevalence, location and effect on visual acuity.
International journal of ophthalmology. Accessed July 20, Myelinated retinal nerve fibers. American journal of ophthalmology. Familial myelinated retinal nerve fibres. Eye London, England. Archives of Ophthalmology. Accessed July 22, Morphological consequences of myelination in the human retina.
Experimental eye research. Evidence that the lamina cribrosa prevents intraretinal myelination of retinal ganglion cell axons. Journal of neurocytology. A matter of identity: transcriptional control in oligodendrocytes. Accessed May 28, Accessed May 22, Myelinated nerve fibres. In: Heredity in Ophthalmology. St Louis, MO: Mosby; — GAPO syndrome: four new patients with congenital glaucoma and myelinated retinal nerve fiber layer.
American journal of medical genetics. Part A. A new syndrome of myelinated nerve fibers, vitreoretinopathy, and skeletal malformations. Archives of ophthalmology. Characteristics of myelinated retinal nerve fiber layer in ophthalmic imaging: findings on autofluorescence, fluorescein angiographic, infrared, optical coherence tomographic, and red-free images. JAMA ophthalmology. Accessed June 30, Syndrome of myelinated retinal nerve fibers, myopia, and amblyopia: a review.
Survey of ophthalmology. Accessed June 18, Clinical neuro-ophthalmology. Wilkins W and, ed. Baltimore; —9. This adds further economy of space and energy. On the other hand the high level of complexity of the CNS white matter makes it vulnerable. There are several different kinds of disease affecting myelinated fibre tracts, particularly with respect to CNS white matter.
The constricted nodal axon is encircled by perinodal astrocytic processes which contain large gliosomes and emit delicate processes towards the nodal axolemma. One astrocyte may project to several nodes. The node gap contains a polyanionic extracellular material. These bodies probably form through budding off from the paranodal myelin sheath.
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