Central nervous system myelin

The expression of all three PPAR isotypes peaks in the rat central nervous system between days 13.5-18.5 of gestation, and while expression of both PPARa and PPARy decline post-natally, expression of PPARS remains high (except for the retina, where all three isoforms are expressed in the adult rodent). An important role for PPARS in CNS development is underscored by the occurrence of defective myelination in the PPARS-null mouse. 

The transport of information from sensors to the central nervous system and of instructions from the central nervous system to the various organs occurs through electric impulses transported by nerve cells (see Fig. 6.17). These cells consist of a body with star-like projections and a long fibrous tail called an axon. While in some molluscs the whole membrane is in contact with the intercellular liquid, in other animals it is covered with a multiple myeline layer which is interrupted in definite segments (nodes of Ranvier). The Na+,K+-ATPase located in the membrane maintains marked ionic concentration differences in the nerve cell and in the intercellular liquid. For example, the squid axon contains 0.05 MNa+, 0.4 mK+, 0.04-0.1 m Cl-, 0.27 m isethionate anion and 0.075 m aspartic acid anion, while the intercellular liquid contains 0.46 m Na+, 0.01 m K+ and 0.054 m Cl-. 

Oligodendrocytes are myelin-producing cells in the central nervous system 13... 

The composition of myelin is well characterized because it can be isolated in high yield and purity by subcellular fractionation 56 Central nervous system myelin is enriched in certain lipids 56 Peripheral and central nervous system myelin lipids are qualitatively similar 58... 

Central nervous system myelin contains some unique proteins 58 Peripheral nervous system myelin also contains unique proteins 63 Some classically defined myelin proteins are common to both peripheral and central myelin 64... 

Central nervous system myelin is enriched in certain lipids. Table 4-1 lists the composition of bovine, rat, and human myelin compared to bovine and human white matter, human gray matter, and rat whole brain [1] (see Ch. 3). While there are no absolutely myelin-specific lipids, cerebroside (galactosyl ceramide) is the most typical of myelin. With the exception of early development,... 

TABLE 4-1 Composition of central nervous system myelin and brain... 

Peripheral and central nervous system myelin lipids are qualitatively similar. However, there are quantitative differences. PNS myelin has less cerebroside and sulfatide and considerably more sphingomyelin than CNS myelin. Of interest is the presence of the LM1 ganglioside, sialosyl-lactoneotetraosylceramide, as a characteristic component of myelin in the PNS of some species. These differences in lipid composition between CNS and PNS myelin are not, however, as dramatic as the differences in protein composition discussed below. 

Baumann, N. and Pham-Dinh, D. Biology of oligodendrocyte and myelin in the mammalian central nervous system. Physiol. Rev. 81, 871-927, 2001. 

Central nervous system myelin contains molecules that inhibit neurite growth 520... 

Central nervous system myelin contains molecules that inhibit neurite growth. One of the major obstacles to new neurite outgrowth in the adult CNS is the presence... 

Nogo-A is a potent inhibitor of neurite growth and blocks axonal regeneration in the central nervous system. Early in vitro experiments showed that neurite outgrowth was impeded across a culture dish coated with CNS myelin whereas neurites would actively grow on a... 

The human leukodystrophies are inherited disorders of central nervous system white matter. These disorders are characterized by a diffuse deficiency of myelin caused by a variety of genetic lesions and often manifest before 10 years of age (Table 38-1). Some are caused by mutations in the PLP gene and resemble the PLP animal mutants described in Chapter 4 [ 1,23]. As with the animal models, depending on the nature of the mutation, they vary from a severe form in connatal Pelizaeus-Merzbacher disease (PMD) through an intermediate phenotype in classical PMD to a mild phenotype in spastic paraplegia. It is noteworthy that some mutations of the PLP gene also cause a peripheral neuropathy [24], very probably related to the expression of low levels of PLP in peripheral nerve (see Ch. 4). 

In Chapter in we drew attention to the fact that some nerve fibres are myelinated. It has been suggested that the pseudocholinesterase of the central nervous system may be concerned in myelin metabolism and that inhibition of pseudo-cholinesterase... 

Figure 14.4 Different types of glial cells. Astrocytes connect capillaries and neurones. Fibrous astrocytes, with less branching and more filamentous processes, occur mainly in white matter while protoplasmic astrocytes are located principally in the grey matter. Oligodendrocytes form the myelin sheath by wrapping themselves around axons. The connection between the myelin sheath and the oligodendrocyte is permanent and provides material for the myelin sheath. Microgliocytes (microglia) are the phagocytes of the nervous system. The ciliated ependymal cells line the cavities of the central nervous system.

Experiments on the physiological and biochemical mechanisms of action suggest that bromethalin uncouples oxidative phosphorylation in central nervous system mitocondria(19). This could lead to a decreased production of ATP, a diminished activity of Na /K ATPase, and a subsequent fluid build up manifested by fluid-filled vacuoles between the myelin sheaths. This vacuole formation in turn leads to an increased cerebrospinal fluid pressure and increased pressure on the nerve axons, yielding a decrease in nerve impulse, paralysis, and death. 

Multiple sclerosis (MS) is the most frequent inflammatory demyeli-nating disease of the central nervous system that affects worldwide about 2.5 million people with no cure. Myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis (MOG-induced EAE) in DA rats is an appropriate model for therapeutic testing, sharing many features with human multiple sclerosis. 

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