Myelin synthesis

Die neurological disorder associated with severe vitamin B12 deficiency is termed funicular myelitis. Vitamin B12 deficiency leads to disturbed choline-, phospholipid-, and nucleic-acid synthesis, resulting in spinal marrow damages. Disturbed myelin synthesis finally causes irreversible neurological failure. In addition, there are psychiatric disturbances (disturbed memory, apathy). 

In the periphery PROG and PREG may well have an important trophic action since their production in Schwann cells has been shown to result in increased myelin synthesis in regenerating rat sciatic nerve and cultured dorsal root ganglia (see Koenig et al. 1995). 

Canavan s disease is the result of a deficiency of the enzyme that breaks down N-acetylaspartate, an important donor of acetyl groups for brain myelin synthesis 682... 

Down-regulation of myelin synthesis pathway genes. 

Pharmacology Vitamin B-12 is essential to growth, cell reproduction, hematopoiesis, nucleic acid, and myelin synthesis. Sources of vitamin B 2 include liver, meat, fish,... 

Mechanism of Action Acts as a coenzyme for various metabolic functions, including fat and carbohydrate metabolism and protein synthesis. Therapeutic Effect Necessary for cell growth and replication, hematopoiesis, and myelin synthesis. Pharmacokinetics In the presence of calcium, absorbed systemically in lower half of ileum. Initially, bound to intrinsicfactor this complex passes down intestine, binding to receptor sites on ileal mucosa. Protein binding High, Metabolized in the liver. Primarily eliminated unchanged in urine. Half-life 6 days. 

The diseases considered here affect only a small fraction of the problems in the catabolism of body constituents. On the other hand, fewer cases are on record of deficiencies in biosynthetic pathways. These are more often absolutely lethal and lead to early spontaneous abortion. However, blockages in the biosynthesis of cerebrosides are known in the special strains of mice known as Jimpy, Quaking, and msd (myelin synthesis deficient).377 378 The transferases (points 11 and 12 of Fig. 20-11) are not absent but are of low activity. The mice have distinct neurological defects and poor myelination of nerves in the brain. 

Using this system, Hamburg (13) could show an acceleration of myelinogenesis by (1,5 to 3 yg/ml) addition. The mechanism whereby influences myelination includes (a) differentiation of the neuroglial cell population responsible for myelin synthesis (38), (b) induction of such differentiated cells to synthesize myelin components, and (c) assembling of the various components to form the complex myelin membrane. Studies are underway to examine the latter possibilities. 

Mental depression, which again may be related to either acetylcholine deficit or impaired myelin synthesis. 

Garbay B, Heape AM, Sargueil F, Cassagne C (2000) Myelin synthesis in the peripheral nervous system. Prog Neurohiol 61 267-304. 

Coating of axons by myelin sheets produced by oligodendrocytes (in the CNS) and Schwann cells (in the PNS) provide electrical insulation and make transmissions along the axon more rapid [97]. The peak level of myelin synthesis in vivo takes place in the second week postnatally in rats and during the last trimester in humans [10]. However, the process of myelin formation continues during development into adulthood making the nervous system sensitive to myelination disrupters for an exceptionally long period [98]. 

Estimates of the rate of myelin synthesis can be obtained in vitro from the measurement of cerebroside synthesis, which increases fourfold from day 10 to day 20 in the rat and then slowly decreases along with the overall rate of myelin synthesis. In vivo studies employing radiolabeled precursors of specific myelin components, such as sulfate into sulfatide, yield results similar to those obtained in vitro. In situ studies with tissue slices confirm in vitro and in vivo experiments. These studies also indicate that the appearance of... 

Patients with classic PKU nsnally appear normal at birth. If the disease is not recognized and treated within the first month of life, the infant gradnally develops varying degrees of irreversible mental retardation (IQ scores freqnently nnder 50), delayed psychomotor matnration, tremors, seiznres, eczema, and hyperactivity. The nenrologic seqnelae may result in part from the competitive interaction of phenylalanine with brain amino acid transport systems and inhibition of neurotransmitter synthesis. These biochemical alterations lead to impaired myelin synthesis and delayed nenronal development, which result in the clinical picture in patients such as Piquet Yuria. Because of the simplicity of the test for PKU (elevated phenylalanine levels in the blood), all newborns in the United States are required to have a PKU test at birth. Early detection of the disease can lead to early treatment, and the nenrologic conseqnences of the disease can be bypassed. 

Early malnutrition in rats and humans, however, interferes with cellular proliferation in the developing brain, delays cell migration and retards myelin synthesis [155]. 

Several investigators (Mills and Williams, 1962 Prohaska and Wells, 1974) have observed a marked decrease in the copper content and cytochrome c oxidase activity of neural tissue from copper-deficient animals. Cytochrome c oxidase is a copper-dependent enzyme and the terminal oxidase in the respiratory chain of mitochondria. These facts have led to speculation that the primary lesion in neonatal ataxia is the depression of cytochrome c oxidase, which leads to a diminution of aerobic metabolism and a subsequent decrease in phospholipid and myeline synthesis. Although this hypothesis seems tenable definitive evidence linking the activity of neural cytochrome c oxidase to the production of myelin is lacking. 

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