Myelination in brain

Further elongation of erucic acid results in the formation of nervonic acid (24 1 ), which is an important component of the myelin in brain and nerve tissue (Martinez and Mougan, 1998). It has been suggested that dietary consumption of nervonic acid could support the synthesis and function of myelin (Sargent et al., 1994), which could be relevant therapeutically for individuals suffering from danyelinating disorders. Like erucic acid, nervonic acid also has a number of potential industrial uses, for example, as a lubricant or a feedstock for polyester synthesis (Taylor et al., 2009a). 

In the chloride shift, Ck plays an important role in the transport of carbon dioxide (qv). In the plasma, CO2 is present as HCO, produced in the erythrocytes from CO2. The diffusion of HCO requires the counterdiffusion of another anion to maintain electrical neutraUty. This function is performed by Ck which readily diffuses into and out of the erythrocytes (see Fig. 5). The carbonic anhydrase-mediated Ck—HCO exchange is also important for cellular de novo fatty acid synthesis and myelination in the brain (62). 

Isaacson LG, Taylor DH. 1989. Maternal exposure to 1,1,2-trichloroethylene affects myelin in the hippocampal formation of the developing rat. Brain Res 488 403-407. 

Nye JS, Voglmaier S, Martenson RE, Snyder SH. Myelin basic protein is an endogenous inhibitor of the high affinity cannabinoid binding site in brain. J Neurochem 1988 50 1170-1178. 

Certain enzymes shown to be present in myelin could be involved in ion transport. Carbonic anhydrase has generally been considered a soluble enzyme and a glial marker but myelin accounts for a large part of the membrane-bound form in brain. This enzyme may play a role in removal of carbonic acid from metabolically active axons. The enzymes 5 -nucleotidase and Na+, K+-ATPase have long been considered specific markers for plasma membranes and are found in myelin at low levels. The 5 -nucleotidase activity may be related to a transport mechanism for adenosine, and Na+, K+-ATPase could well be involved in transport of monovalent cations. The presence of these enzymes suggests that myelin may have an active role in ion transport in and out of the axon. In connection with this hypothesis, it is of interest that the PLP gene family may have evolved from a pore-forming polypeptide [9],... 

Not all neurons have NFs. Indeed, one entire phylum in the animal kingdom, arthropods, expresses only type V nuclear lamins so arthropod cells have no IF cytoskeletal structures at all. In addition, mature oligodendrocytes lack IFs although their embryonic precursors contain vimentin. Clearly, the IFs are not essential for cell survival. Yet, in large myelinated fibers, NFs make up the bulk of axonal volume and represent a substantial fraction of the total protein in brain. In most organisms, IFs in both glia... 

About 40% of this population express markers of oligodendrocytes, and a similar proportion have astrocytic markers. To test the potential of these cells in vitro, ES cells propagated in this fashion were transplanted into the spinal cord or cerebral ventricles of myelin-deficient rats. Two weeks after transplantation, ES derived cells were present in the dorsal columns of the spinal cord both at the implant and several millimeters in both directions from that site. The mouse origin of the ES cells transplanted into rat was confirmed by analysis of mouse satellite DNA in the grafts. Similarly, intraventricular transplanted cells formed myelin in multiple brain regions [29]. These and other results support the further study of stimulated ES cells for potential therapies in the nervous system. 

Imbalances of brain amino acids may hinder the synthesis of brain lipids, leading to a diminution in the rate of myelin formation. Decreases of lipids, proteolipids and cerebrosides (Ch. 3) have been noted in several of these syndromes, e.g. maple syrup urine disease, when intra-myelinic edema is a prominent finding, particularly during the acute phase of metabolic decompensation [9]. Pathological changes in brain myelin are common, especially in infants who die early in life. The fundamental... 

Akiyama, Y., Honmou, 0., Kato, T., Uede, T., Hashi, K., Kocsis, J.D. (2001). Transplantation of clonal neural precursor cells derived from adult human brain establishes functional peripheral myelin in the rat spinal cord. Exp Neurol, 167, 27-39. 

Tsukada (30) have examined developmental changes of the enzyme in chick brain and spinal cord. Enzymic activity appears at about the eighteenth day of incubation and increases rapidly until 3 days after hatching in the brain and between 18 and 21 days of incubation in the spinal cord. These are precisely the periods of active myelination in the brain and spinal cord of the chick, respectively. Similarly, brain tissue of the newborn rat is devoid of cyclic phosphate diesterase activity it appears at about 8 days after birth and increases dramatically between the tenth and thirty-fifth day of life (29). This coincides precisely with the development of myelin in this species. The diesterase is essentially absent in the brain of the jimpy mouse (31), a lethal mutant devoid of myelin in the central nervous system. It is also absent from the spinal cord of this mutant. The enzyme is about 50% deficient in brain tissue of the quaking mouse (29), a mutant with partial deficiency of myelin. There is no activity in nerve fibers and ganglia from a variety of invertebrates such as squid, octopus, crab, shrimp, and starfish. Nerve tissue in these organisms is nonmyelinated. All these observations point to an intimate association of the enzyme with myelin in vivo. 

Biochemical, Morphological, and Regulatory Aspects of Myelination in Cultures of Dissociated Brain Cells from Embryonic Mice... 

The temporal appearance of myelin-related lipids and enzymes in the cultures of dissociated fetal mouse brain cells mimics the temporal development of these parameters in normal mouse or rat brain (12, 5, 29, 28). The types of myelin-related lipids and the order of magnitude of the activities of the enzymes producing some of these lipids are the same as those found in brain in vivo (30, 29, 28). 

Demyelination. The role of myelin in the nervous system is to aid in signal transduction. Myelin acts like an electrical insulator by preventing loss of ion current, and intact myelin is critical for the fast saltatory nerve conduction discussed above. Neurotoxicants that target the synthesis or integrity of PNS myelin may cause muscle weakness, poor coordination, and paralysis. In the brain, white matter tracts that connect neurons within and between hemispheres may be destroyed, in a syndrome known as toxic leukoencephalopathy. A multifocal distribution of brain lesions is reflected in mental deterioration, vision loss, speech disturbances, ataxia (inability to coordinate movements), and paralysis. 

One problem with long-term inhalant abuse is that it can break down myelin in the body, according to a NIDA report. Myelin is a fatty tissue that surrounds many of the body s nerve cells called neurons. The nerve cells in the brain and spinal cord are like a command central for the body. They transmit messages that control just about everything the body does. If the myelin breaks down, the nerve cells may not be able to transmit messages. 

Eto Y, Suzuki K, Suzuki K. 1971. Lipid composition of rat brain myelin in triethyl tin-induced edema. J Lipid Res 12 570-579. 

Similar to Scd2 in mice (Kaestner et al., 1989), desatl mRNA is found at higher levels in brain. The role of the desaturase in brain is to supply unsaturated fatty acids necessary for the synthesis of membrane phospholipids, particularly for myelination. 

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