Which cells produce myelin

An axon is a tube-like structure that propagates the integrated signal to specialized endings called axon terminals. These terminals in turn synapse on other neurons, muscle, or target organs. Chemicals released at axon terminals allow signals to be communicated to these other cells. Neurons usually have one or two axons, but some neurons, like amacrine cells in the retina, do not contain any axons. Some axons are covered with myelin , which acts as an insulator to minimize dissipation of the electrical signal as it travels down the axon, greatly increasing the speed on conduction.

This insulation is important as the axon from a human motor neuron can be as long as a meter—from the base of the spine to the toes. The myelin sheath is not actually part of the neuron. Myelin is produced by glial cells. Along the axon there are periodic gaps in the myelin sheath. It is important to note that a single neuron does not act alone—neuronal communication depends on the connections that neurons make with one another as well as with other cells, like muscle cells.

Dendrites from a single neuron may receive synaptic contact from many other neurons. For example, dendrites from a Purkinje cell in the cerebellum are thought to receive contact from as many as , other neurons. There are different types of neurons, and the functional role of a given neuron is intimately dependent on its structure. There is an amazing diversity of neuron shapes and sizes found in different parts of the nervous system and across species , as illustrated by the neurons shown in Figure While there are many defined neuron cell subtypes, neurons are broadly divided into four basic types: unipolar, bipolar, multipolar, and pseudounipolar.

Figure Unipolar neurons have only one structure that extends away from the soma. These neurons are not found in vertebrates but are found in insects where they stimulate muscles or glands.

A bipolar neuron has one axon and one dendrite extending from the soma. An example of a bipolar neuron is a retinal bipolar cell, which receives signals from photoreceptor cells that are sensitive to light and transmits these signals to ganglion cells that carry the signal to the brain.

Multipolar neurons are the most common type of neuron. Each multipolar neuron contains one axon and multiple dendrites. Multipolar neurons can be found in the central nervous system brain and spinal cord. An example of a multipolar neuron is a Purkinje cell in the cerebellum, which has many branching dendrites but only one axon. Pseudounipolar cells share characteristics with both unipolar and bipolar cells. A pseudounipolar cell has a single process that extends from the soma, like a unipolar cell, but this process later branches into two distinct structures, like a bipolar cell.

Most sensory neurons are pseudounipolar and have an axon that branches into two extensions: one connected to dendrites that receive sensory information and another that transmits this information to the spinal cord. At one time, scientists believed that people were born with all the neurons they would ever have. Research performed during the last few decades indicates that neurogenesis, the birth of new neurons, continues into adulthood.

Neurogenesis was first discovered in songbirds that produce new neurons while learning songs. For mammals, new neurons also play an important role in learning: about new neurons develop in the hippocampus a brain structure involved in learning and memory each day. While most of the new neurons will die, researchers found that an increase in the number of surviving new neurons in the hippocampus correlated with how well rats learned a new task. Interestingly, both exercise and some antidepressant medications also promote neurogenesis in the hippocampus.

Stress has the opposite effect. How do scientists identify new neurons? A researcher can inject a compound called bromodeoxyuridine BrdU into the brain of an animal. A technique called immunohistochemistry can be used to attach a fluorescent label to the incorporated BrdU, and a researcher can use fluorescent microscopy to visualize the presence of BrdU, and thus new neurons, in brain tissue.

This site contains more information about neurogenesis, including an interactive laboratory simulation and a video that explains how BrdU labels new cells. While glia are often thought of as the supporting cast of the nervous system, the number of glial cells in the brain actually outnumbers the number of neurons by a factor of ten. Neurons would be unable to function without the vital roles that are fulfilled by these glial cells.

Glia guide developing neurons to their destinations, buffer ions and chemicals that would otherwise harm neurons, and provide myelin sheaths around axons. In the allelic mouse mutant, jimpy msd, there are similar ultrastructural alterations in myelin as seen in the jimpy mouse, but about twice as many glial cells escape premature degeneration Billings-Gagliardi et al. The rumpshaker mutant is the result of a novel mutation of the PLP gene Schneider et al.

Rumpshaker mice have more myelin than other dysmyelinated mutants and the degree of dysmyelination varies among CNS regions, with early myelinated regions appearing normal whereas late myelinating regions are severely hypomyelinated.

The oligodendrocytes appear differentiated and most escape apoptotic cell death resulting in a normal complement of mature oligodendrocytes Griffiths et al. The rumpshaker mutation appears to allow the oligodendrocyte to survive but somehow interferes with its ability to normally deposit PLP in the myelin membrane Schneider et al.

Although sparse, some myelin sheaths subsist in the rumpshaker mutants and these show selective immunostaining for DM20 Schneider et al. These findings suggest that DM20 may serve a critical purpose in glial cell development that is distinct from any function in myelin formation and maintenance. P 0 -deficient mice have been generated by homologous recombination of the P 0 gene in mouse embryonic stem cells with the cloned gene and subsequent generation of germline chimeric mice Giese et al.

Animals lacking one functional copy of the P 0 gene are phenotypically normal, but the homozygotes develop a behavioral phenotype by the third week of life. These mice show a body tremor and dragging movements of the hindlimbs. There is no evidence of paralysis or seizures and the mutants have a normal life span. Histologically, the deficit is characterized by the inability of the Schwann cell to assemble a compacted multilamellar PNS myelin sheath.

The high degree of variability in the pathology is thought to be due to the intervening actions of other proteins such as cell adhesion molecules MAG; N-CAM , and perhaps other myelin proteins. Using promoter and regulatory regions of the P 0 gene in a fusion gene construct, Schwann cells were destroyed when they began to express P 0 , after associating in a ratio with axons Messing et al.

The behavioral phenotype of the Schwann cell—ablated mice was similar to the phenotype displayed in the homogygous P 0 mutants. A proliferation of nonmyelin—forming Schwann cells was induced along with skeletal muscle atrophy.

The PMP gene encodes an integral membrane protein specific to Schwann cells 22 kDa peripheral myelin protein believed to be important for normal Schwann cell development Spreyer, et al. Histologically, the majority of large caliber axons in the sciatic nerve are devoid of a myelin sheath and, if present at all, these are abnormally thin and relatively uncompacted Henry and Sidman, The total number of Schwann cells is dramatically increased at the time of segregation of axons, and myelin deposition is arrested.

In the absence of PNS myelin, the mice display a behavioral phenotype characterized by a coarse-action tremor that begins at the end of the second postnatal week and results in moderate quadriparesis and a waddling gate.

Under controlled conditions, these animals can experience a normal life span. The quaking mouse qk; mouse chromosome 17 is the result of an autosomal recessive mutation Sidman et al. The myelin deficiency, characterized by fewer than normal myelin lamellae, is predominately in the brain and spinal cord, although a lack of normal compaction and enlarged intraperiod lines of some myelinated fibers has been noted in the PNS as well Trapp, Interestingly, the distribution of MAG is shifted from the innermost myelin layer facing the axon to throughout the compact myelin sheath.

Myelin mutants in a number of other species besides humans and mice have also been described see Duncan, , for detailed discussion. These include X-linked mutations in the dog shaking pup, Griffiths et al. As noted previously, myelination is a critical process in the maturation of the nervous system.

It involves the synthesis of an enormous amount of specialized membrane within a relatively short period of time. Insults occurring during the period of proliferation of myelinating cells may be especially disruptive, as this may lead to an irreversible deficit of myelin-forming cells and consequent permanent hypomyelination.

Perturbation of myelination at a later stage may result in a myelin deficit that can be reversed. The morphologic term myelinopathy describes damage to white matter or myelin, and disorders of myelin can be classified by a number of different factors. In addition, effects on myelin can sometimes be delineated as the result of a primary effect on myelin itself or the myelinating glial cell.

Myelin loss due to a primary insult to myelin or the myelinating cell are termed primary demyelination. There are a number of factors relevant to selective targeting of various toxic or metabolic insuits to myelin for discussion, see Morell, et al.

An intact axon is a prerequisite for maintenance of normal myelin; alterations in myelin due to an effect on the neuron or the underlying axon is termed secondary demyelination. Secondary demyelination is an inevitable consequence of serious damage to neurons supporting myelinating axons or to axonal transcetion or crush Wallerian degeneration. However, the distinction between primary and secondary demyelination is often somewhat vague; the basis for this distinction usually involves morphologic evidence of the initial target site.

The term hypomyelination is used to describe developmental alterations of myelination in which an insufficient amount of myelin accumulates. Hypomyleination can be the result of disease processes, undernutrition, or toxic insult. The term dysmyelination , when used in its strictest sense, refers to certain inborn errors of metabolism in which a block in the breakdown of a myelin lipid causes accumulation of myelin of an abnormal composition which eventually leads to a collapse and degeneration of myelin , but it is also in wide use as a general descriptor of situations characterized by any abnormalities in myelin.

Some specific myelinopathies that are preferential to developing organisms are discussed later in this chapter. Additional toxicants have been demonstrated to disturb myelin in the adult animal and the morphologic descriptions and mechanistic processes involved have been previously discussed Morell, , Morell and Toews, In the human infant, several studies have provided evidence supporting the concept of a critical period from birth to about 2 years of age, during which time the nervous system is most vulnerable to malnutrition.

The production of neurons is virtually completed by about the midpoint of gestation, but glial cell production continues through the end of gestation into the second postnatal year. The vulnerability of the developing nervous system to various factors is determined by the developmental stage of the cellular activities targeted by a specific insult. The effects of an agent or condition may vary depending on the agent, the time of insult during development, and the species under study Dobbing, et al.

Depending on the developmental process ongoing at the time of exposure, alterations can be produced in either the number of neurons and extent of axonal arborizations, the number of glial cells, or the degree of myelination.

Following severe nutritional deprivation during lactation and post-weaning, total brain galactolipids, cholesterol, and lipid phosphorus showed a slower rate of accumulation Krigman and Hogan, Myelin recovered from undernourished rats was normal in lipid composition but siginificantly reduced in total amount Fishman et al.

A reduced proportion of basic and proteolipid protein was seen in myelin isolated from undernourished rats at postnatal days 15 and 20, but the composition was similar to normals by postnatal day These studies suggested that undernutrition produced a delay in myelin maturation.

Morphologic examination of animals undernourished from birth showed a decreased number of mature oligodendroglia and poorly stained myelin Bass, et al. The number of myelin lamellae per axon and the number of myelin lamellae for a given axon diameter were both lower Krigman and Hogan, Some studies suggest that in some cases, myelination is able to catch-up and achieve normal levels once unrestricted feeding is initiated.

Rats deprived by an increased litter size rapidly gained body and brain weight and normal brain lipid composition within 3 weeks after weaning to an unrestricted diet Benton et al. However, nutritional deprivation during the first 21 days of life resulted in reduced levels of total brain lipids, cerebrosides, cholesterol, and PLP, and this deficit persisted through days of age Bass et al.

Similar persistent myelin deficits were found in brains of rats subjected to either moderate or severe food deprivation during the first 30 days of life Toews et al. Although metabolic studies showed that after 6 days of free feeding following 20 days of postnatal starvation, incorporation of labeled precursors into myelin proteins was higher than in animals starved for the entire 26 days, and it was still depressed relative to controls Wiggins et al. Severe underfeeding in rats from 1 to 14 days of age resulted in a lasting significant deficit in myelin, even with rehabilitation Wiggins and Fuller, Overall, these studies point to the possibility of irreversible deficits in myelin resulting from nutritional deficiencies during development.

Additional studies suggest the most vulnerable period for myelin may be the time of oligodendroglial proliferation. Animals deprived during this period are left with a permanent deficit of myelin-forming cells, resulting in irreversible hypomyelination Wiggins and Fuller, Apparently, once normal numbers of oligodendroglia have been formed, the process of myelin formation itself is somewhat more capable of nutritional rehabilitation.

Similar effects can be found with a specific nutritional manipulation of depleting protein in the diet. In rats subjected to a protein and calorie deficiency during gestation and lactation, glial numbers were greatly reduced, and by postnatal day 19 the majority of cells in the corpus callosum appeared to be glioblasts rather than differentiated oligodendroglia Robain and Ponsot, An early postnatal protein deficiency resulted in reduced levels of brain myelin and an altered myelin composition in rats Nakhasi et al.

The MAG persisted in its higher molecular weight form longer than normal, suggesting that protein deficiency results in a delay in development and maturation of the myelination process Druse and Krett, Animals raised on a fat-deficient diet are able to synthesize all fatty acids except the essential fatty acids linoleic and linolenic acid families.

Essential fatty acid deficiency induced prenatally in the mothers and postnatally in the offspring resulted in lower brain weights White et al. In the optic nerve of essential fatty acid—deficient rats, vacuolation, intramyelinic splitting, and Wallerian degeneration were present Trapp and Bernsohn, Several studies have demonstrated hypomyelination in the offspring of copper-deficient mothers DiPaolo, et al. Thyroid hormones influence the temporal onset of myelination and its compositional maturation.

It is thought, however, that hypothyroidism does not exert a specific effect on myelin but rather delays myelin development and maturation Dalal, et al.

Whereas hypothyroidism resulted in a 1—2 day delay of myelinogenesis with prolonged immature myelin formation, it eventually attained a normal composition, although the myelin deficit persisted. A classic example of differential susceptibility of the developing organism to the effects of an environmental chemical is that of inorganic lead exposure. Children are more vulnerable to lead in terms of external exposure sources, internal levels of lead, and timing of exposures during development.

At high exposure levels, lead induces encephalopathy in children and can be life threatening. Experimental animal studies have allowed examination of various specific target sites and processes of development susceptible to lead toxicity Krigman et al. During development, the process of CNS myelination shows an increased vulnerability to lead exposure. The amount of lead that accumulates in the brain of the developing animal during lactation can be as much as 4 times higher than brain levels in the lactating dam receiving lead in the drinking water.

Under these conditions, myelin was significantly reduced; however, the relationship between the axon diameter and myelin lamellae remained normal, suggesting that the hypomyelination was the result of altered axonal growth Krigman et al.

Direct administration of lead via to pups intubation from 2 to 30 days of age resulted in a reduction of myelin accumulation in the forebrain and optic nerve.

These effects were not due to undernutrition, as the accumulation of brain myelin was decreased significantly relative to controls undergoing a similar degree of malnourishment Toews et al. In developing rats, there is a synergistic interaction between lead exposure and mild malnutrution induced by milk deprivation with respect to decreasing the normal developmental accumulation of myelin Harry et al.

This interaction appeared to be more prevalent in females as compared to males. The decrement in myelin induced by development exposure to inorganic lead is a long-lasting effect that persists into adulthood Toews, et al.

Myelination is not necessarily the most sensitive target for lead as low doses sufficient to produce some microscopically discernible hemorrhagic encephalopathy in the cerebellum of young rats did not depress myelination Sundstrom and Karlsson, ; this hemorrhagic encephalopathy may be related to concentration of lead in brain capillaries Toews et al. The pathologic effect varies with the age of the animal Suzuki, Young rats exposed to TET develop severe spongious white matter similar to that seen in the adult, but with the absence of major clinical signs seen in the adult Suzuki, , Blaker, et al.

It is thought that the severe paralysis seen in the adult animal is due in part to the intracranial pressure developed during severe edema, whereas the open cranial sutures in the young rat may allow for edema in the absence of increased pressure.

When newborn rats are exposed to TET, brains became swollen and petechial hemorrhages are observed, particularly in the cerebellum. Necrotic cells were found diffusely throughout the brain Watanabe, When older postnatal day 8 animals were exposed, both the hemorrhagic and necrotic changes occurred, but damage was also seen in the myelinated fibers of the brain stem and cerebellum. Although the morphologic alterations in myelin dissipate with time, biochemical evidence suggests that the amount of myelin produced is decreased and that this myelin deficit persists through adulthood Blaker, et al.

In studies using radioactive tracer, Smith demonstrated that it is the newly forming CNS myelin that is preferentially susceptible to degradation by TET.

Interestingly, administration of TET to quaking mice did not produce intramyelinic edema Nagara et al. When young animals are exposed to trialkyllead, the process of myelination is inhibited Konat and Clausen, Unlike triethyltin, this impairment in myelinogenesis is not accompanied by edema of white matter. The impairment appears to be primarily in the deposition of myelin rather than in the program for myelination, as the protein composition of forebrain myelin isolated from triethyllead-intoxicated young rats was normal Konat and Clausen, In vitro studies suggest that the alteration involves posttranslational processing and transport of integral membrane proteins, processes particularly important for myelin proteins during development Konat and Clausen, , Konat and Offner, Both CNS and PNS myelin show a severe white matter edema following exposure, and young rats are more vulnerable than adults Towfighi et al.

In young rats, edema of the myelin sheath becomes evident after postnatal day 15, probably because the myelin membrane provides a hydrophobic reservoir for accumulation of this toxic compound and thereby becomes a significant site for fluid accumulation Nieminen et al. Developmental exposure results in a decrease of the normal accumulation of myelin during development Matthieu et al.

In day-old rats nursed by mothers fed hexachlorophene, there was a decrease in myelin yield, yet the myelin composition remained normal. Degeneration caused by this antimetabolite involves myelin, neurons, astrocytes, and oligodendroglia. In young animals injected with 6-aminonicotinamide, the PNS shows a selective swelling of Schwann cell cytoplasm at the inner surface of the myelin sheath.

The nerve is compressed by the swelling and results in an overgrowth of the myelin sheath Friede and Bisch-hausen, Young ducklings fed a diet containing IHN developed a wobbling gait and head tremor after 2 weeks, progressing to ataxia and inability to stand Lampert and Schochet, Examination of the CNS showed spongy degeneration of the myelin-containing white matter. Cuprizone bis -cyclohexanoneoxalyhydrazone is a copper chelator that results in CNS demyelination following dietary exposure to weanling mice.

Deficits in adenosine triphosphate ATP production secondary to reduced activity of cytochrome oxidase a copper-requiring enzyme may lead to alterations in energy-requiring ion transport mechanisms, but the underlying reason for targeting of this compound to CNS myelin is not clear. Interestingly, cuprizone inhibits carbonic anhydrase, an enzyme present in myelin, and this inhibition takes place well before any demyelination is observed Komoly et al.

In experimental studies of cuprizone neurotoxicity, mRNA for MAG, a protein located at the myelin—axonal interface, is down-regulated during demyelination and returns to normal levels following cessation of exposure Fujita et al.

The mRNA for this glycoprotein exists in two major splice variants that are both severely down-regulated. On recovery, one splice variant returns to normal levels whereas the exposure to cuprizone 9 weeks or longer in mice results in irreversible demyelination Tansey et al.

Exposure of weanling rats to a diet containing tellurium element 52 leads to a highly synchronous demyelinating peripheral neuropathy Lampert and Garrett, , Duckett, et al. When tellurium exposure is discontinued, there is rapid and synchronous remyelination.

Although tellurium toxicity in humans is rare, this model is of considerable interest as a system for studying the manner in which a specific metabolic insult can lead to demyelination. Because there is little or no associated axonal degeneration, it has also proved useful for examining events and processes related to PNS remyelination, independently of processes related to axonal regeneration.

Inclusion of 1—1. This demyelination results in a peripheral neuropathy characterized by hindlimb paresis and paralysis. Older rats are much more resistant to tellurium, and the CNS is generally not affected, although some pathologic alterations can be induced with prolonged exposure periods.

The nature of the underlying metabolic insult has been delineated. Tellurium blocks cholesterol synthesis, specifically by inhibiting the enzyme squalene epoxidase, an obligate step in the cholesterol biosynthesis pathway Harry, et al.

Tellurite, a water-soluble oxidized metabolite of the administered insoluble element, is the active species in vitro , effective at micromolar concentrations in a cell-free system Wagner et al. The organotellurium compound dimethyltelluronium dichloride, CH 3 2 TeCl 2 , is also effective in inhibiting squalene epoxidase in cultured Schwann cells and in inducing demyelination when administered intraperitoneally Goodrum, Presumably, the resulting cholesterol deficit in Schwann cells eventually leads to an inability to maintain preexisting myelin and to assemble new myelin; this in turn leads to the observed demyelination.

Although the tellurium-induced inhibition of cholesterol biosynthesis is systemic, deleterious effects are confined largely to the sciatic nerve. In the liver, which supplies cholesterol for most body tissues, the resulting intracellular cholesterol deficit results in a marked upregulation of the cholesterol biosynthetic pathway Toews, et al. This allows normal levels of cholesterol synthesis in this tissue despite considerable inhibition of one of the steps in the synthesis pathway, and normal levels of lipoprotein-associated circulating cholesterol are maintained.

However, unlike many other tissues, the sciatic nerve cannot use circulating cholesterol; all cholesterol required for myelin in the sciatic nerve must be synthesized locally Jurevics and Morell, This fact, coupled with the great demand for cholesterol in the rapidly myelinating PNS at the time of tellurium exposure, may account for the specificity of toxicity observed. Expression of mRNA for myelin proteins is markedly down-regulated during the demyelinating phase of tellurium neuropathy, as is gene expression for enzymes involved in synthesis of lipids enriched in myelin Toews, et al.

Although this enzyme is markedly up-regulated in the liver as expected from the tellurium-induced intracellular sterol deficit , it is down-regulated in the sciatic nerve in concert with other myelin-related genes Toews et al.

Failure to up-regulate the cholesterol biosynthesis pathway in the sciatic nerve is, in fact, probably the major underlying reason for the preferential susceptibility of this tissue. The co-ordinate down-regulation for myelin-related genes seen following exposure to tellurium suggests that gene expression of all proteins involved in myelin synthesis and assembly may be under the co-ordinate control of the overall program for myelination see Morell and Toews, a , Toews, et al.

The coordinate down-regulation of myelin gene expression takes place in all myelinating Schwann cells and not just in those undergoing demyelination Toews et al. Thus, this down-regulation is not just a secondary response to injury but rather reflects the co-ordinate control of myelin gene expression.

When tellurium exposure is discontinued, there is co-ordinate up-regulation of these messages during the remyelinating period. Thus, tellurium toxicity specifically leads to PNS demyelination because 1 synthesis of cholesterol, a major myelin lipid, is severely inhibited; 2 unlike other tissues, peripheral nerve cannot up-regulate the synthesis of cholesterol in response to the tellurium-induced cholesterol deficit; 3 because the PNS is isolated from the circulation by barriers, it cannot use circulating cholesterol derived from the diet or from synthesis in the liver; and 4 there is a particularly high demand for cholesterol in the myelinating PNS at the time of tellurium exposure.

The process of myelination by oligodendroglia in the CNS and by Schwann cells in the PNS represents a complex series of metabolic and cell—biologic events involving intercellular recognition and interaction, adhesion, synthesis, sorting and assembly of specialized myelin membranes, compaction of myelin lamellae, and axonal and possibly glial ion channel reorganization.

The timing of any toxicant exposure or other insult can also differentially effect one or more of these events necessary for normal myelination. Although these processes are best examined in the developing nervous system, a clearer understanding of the biochemistry, molecular biology, and cell biology of these events is also of particular relevance with regards to remyelination in injured adult nervous tissue.

Further delineation of the underlying nature of insults that result from toxic, genetic, nutritional, or other perturbations will also be useful in better understanding these vital processes.

National Center for Biotechnology Information , U. Handbook of Developmental Neurotoxicology. Published online May 9. Arrel D. Guest Editor s : William Slikker, Jr. Guest Editor s : Louis W. Chang, Dr. Copyright and License information Disclaimer. All rights reserved. Elsevier hereby grants permission to make all its COVIDrelated research that is available on the COVID resource centre - including this research content - immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source.

Introduction Normal functioning of the nervous system involves the transmission, processing, and integration of information as nervous impulses. Open in a separate window. Figure 1. Figure 2. Figure 3.

Axon—Glia Interactions during Development and Myelination The tightly programmed sequence of events eventually resulting in the formation of mature compact myelin and the consequent initiation of impulse transmission is regulated by interactions between axons and glial cells at numerous stages see Waxman and Black, , for detailed discussion.

Myelin-Forming Cells and Their Ontogenic Development The ontogenic development of the myelinating Schwann cell lineage has been relatively well-characterized, particularly in rodents. Figure 4. Modified from Mirsky and Jessen [] and Zorick and Lemke [].

B Myelinating oligodendroglial cells of the CNS originate from neuroectodermal cells of the subventricular zones of the developing brain. The earliest precursor cells recognized to date Pre-GD3 stage are proliferative, unipolar cells that express the embryonic neural cell adhesion molecule E-NCAM.

Development continues through a postmigratory but proliferative multipolar pro-oligodendroblast Pro-OL and a Pre-GalC stage, characterized by lack of expression of GalC. Immature OLs then undergo final differentiation into mature oligodendrocytes mature OL , characterized by regulated expression of myelin components such as MBP and PLP and by the synthesis and elaboration of sheets of myelin membrane.

Oligodendrocyte—Myelin Glycoprotein Omgp Oligodendrocyte—myelin glycoprotein Omgp is one of the minor protein components of myelin that appears in the CNS during the period of myelination. Enzymes Associated with Myelin Although myelin initially was believed to be metabolically inert due largely to the very slow metabolic turnover of some of its components and to function exclusively as an electrical insulator, it is now known that the picture is considerably more complex and interesting.

Cytoskeletal Proteins in Myelin and Myelinating Glia The cell surface area of myelin-forming cells is so large as to suggest the need for specialized structures and mechanisms for transporting components between the perikaryon and the remote extensions.

Molecular Aspects of Myelin Synthesis and Assembly Because the structure and composition of myelin is unique, its formation involves activation of a set of unique genes see Lemke, , for details.

Mutant Dysmyelinating Mouse Models In the mouse, terminal differentiation of myelin-forming cells occurs mostly after birth, following establishment of the basic wiring of the nervous system.

Shiverer Mice The shiverer mouse shi, mouse chromosome 18 was one of the first neurologic mouse mutants examined at the molecular—genetic level Roach et al. Jimpy Mice—Dysmyelination and Glial Cell Death The mammalian PLP gene is linked to the X chromosome and defects in this gene are associated with neurologic abnormalities in the mouse and with Pelizaeus—Merzbacher disease in humans. P 0 -Deficient Mice P 0 -deficient mice have been generated by homologous recombination of the P 0 gene in mouse embryonic stem cells with the cloned gene and subsequent generation of germline chimeric mice Giese et al.

Quaking Mice The quaking mouse qk; mouse chromosome 17 is the result of an autosomal recessive mutation Sidman et al. Myelin Mutants in Other Species Myelin mutants in a number of other species besides humans and mice have also been described see Duncan, , for detailed discussion.

Undemutrition In the human infant, several studies have provided evidence supporting the concept of a critical period from birth to about 2 years of age, during which time the nervous system is most vulnerable to malnutrition. Thyroid Deficiency Thyroid hormones influence the temporal onset of myelination and its compositional maturation. Inorganic Lead A classic example of differential susceptibility of the developing organism to the effects of an environmental chemical is that of inorganic lead exposure.

Trialkyllead When young animals are exposed to trialkyllead, the process of myelination is inhibited Konat and Clausen, Isonicotinic Acid Hydrazide IHN Young ducklings fed a diet containing IHN developed a wobbling gait and head tremor after 2 weeks, progressing to ataxia and inability to stand Lampert and Schochet, Cuprizone Cuprizone bis -cyclohexanoneoxalyhydrazone is a copper chelator that results in CNS demyelination following dietary exposure to weanling mice.

Tellurium Exposure of weanling rats to a diet containing tellurium element 52 leads to a highly synchronous demyelinating peripheral neuropathy Lampert and Garrett, , Duckett, et al. Concluding Remarks The process of myelination by oligodendroglia in the CNS and by Schwann cells in the PNS represents a complex series of metabolic and cell—biologic events involving intercellular recognition and interaction, adhesion, synthesis, sorting and assembly of specialized myelin membranes, compaction of myelin lamellae, and axonal and possibly glial ion channel reorganization.

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Sign Up. For Educators Log in. Research and Discoveries. Myelin is a fatty material that wraps around nerve cell projections. In this image, myelin can be seen on either end of the nerve fibers. 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.