NEURONAL METABOLISM 



I8l 9 



MYELINIZATION 



From a study of the formation of various lipids and 

 related substances in mouse brain during embryonic 

 development, an attempt has been made to correlate 

 structural and functional development with chemical 

 composition (34). Before the onset of myelinization 

 at about the 7th day, the brain has attained 60 per 

 cent of its adult weight, 40 per cent of the proteins, 

 50 per cent of the strandin and 30 per cent of the 

 phosphatides. With the development of myeliniza- 

 tion, dendritic aborization and neuroglia occurs a 

 rapid formation of proteolipids, cerebrosides, choles- 

 terol and acetal phosphatides. Since these lipids were 

 either almost or completely absent before myeliniza- 

 tion, it would appear that their formation is a measure 

 of 'white matter events, 5 while strandin may be taken 

 as an index of the development of 'grey matter.' 

 Sphingomyelin has been shown to be almost ex- 

 clusively associated with the nerve sheath and is 

 likewise absent before myelinization ( 105). By the end 

 of the stage of myelinization, the sphingolipids have 

 increased to such an extent that they comprise almost 

 half of the total lipids in brain and spinal cord (34). 

 Gangliosides, on the other hand, are associated with 

 neuronal soma and dendrites (68). It appears as 

 though cerebrosides, cholesterol and sphingomyelins, 

 rather than cephalitis and lecithins, constitute the 

 lipids of the myelin sheath (65). By the application 

 of microchemical techniques to the quantitative 

 histochemistry of brain, it has been shown that in the 

 white matter of the cerebellar cortex (98, 100) and 

 cerebral cortex (99) the cephalitis (probably phos- 

 phatidylserines rather than phosphatidylcthanol- 

 amines) are quantitatively similar to the sphingolipids. 

 In the cerebral cortex the nonphosphorus-containing 

 sphingolipids appear to be the most characteristic 

 lipid of white matter (99, 105), these lipids being 

 found in surprisingly low concentrations in the 

 molecular layers (largely dendritic). 



In recent years, a number of fine physicochemical 

 tools have been used in an attempt to determine the 

 structure of myelin. Polarization and x-ray diffraction 

 studies have revealed myelin to consist of a laminated 

 lipoprotein structure (32, 104). The fatty acid chains 

 of the complex are oriented radially, and the repeating 

 periods of the lipoprotein are amazingly constant 

 (about 180 A) from species to species. The lipoid 

 portion in itself has a laminar structure comprised of 

 a complex of unesterified cholesterol and phospho- 

 lipid (31). By means of infrared spectrophotometry 

 it is possible to distinguish between certain hydro- 



carbon groups, such as CH 2 and CH 3 , within myelin 

 preparations (22). Such analysis permits, among other 

 things, the determination of the deposition of fatty 

 acid in myelin as well as the synthesis of long chain 

 fatty acids from shorter ones. It has also been possible 

 to follow the deposition of myelin in the developing 

 nervous system. 



Myelination proceeds as a layer-by-layer addition 

 of lipid-protein complexes originating from the 

 infolding of the surface membrane of the Schwann 

 cell. Attached to the inner layers as outpocketings 

 into the axoplasm of the spiraling-like structure are 

 numerous mitochondria which are believed either to 

 result from the Schwann cell surface or to be actively 

 engaged in myelinization (46, 47). By means of 

 polarization optics, the neurofibrils of the axoplasm 

 appear to consist of asymmetric submicroscopic 

 particles oriented parallel with the fiber axis (12). 

 The composition of the submicroscopic particles is 

 not known, although they are believed to be micro- 

 somes (10) which can be separated from nerve as a 

 heterogeneous group of spherical particles which are 

 10 to 200 m/i in diameter (6, 10). In addition to their 

 property of birefrigence of How and ability to readily 

 form bead-like threads, the microsomes are rich in 

 enzymes involved in the splitting of adenine nu- 

 cleotides, a readily available source of energy (10). 



STRICTl RAI. ELEMENTS, <;Ri)VV III AMI 

 DIFFERENTIATION 



Among the most promising techniques used in the 

 study of intracytoplasmic chemistry of brain are 

 those of ultraviolet microspectography (28) and x-ray 

 microradiography (29). The methods have been used 

 in the study of lipids, ribose nucleic acid (RNA) and 

 proteins in single neurons from Deiter's nucleus, 

 spinal ganglia and Purkinje cells. The neurons of 

 Deiter's nucleus are characterized by large amounts 

 of lipids and RNA, the lipids comprising about 56 

 per cent of the total weight (io -9 mg per /z 3 ) of a 

 cell and RNA about 25 per cent (17). Purkinje cells 

 contain less than 5 per cent RNA and about 20 per 

 cent lipids, while the protein content appears to 

 differentiate the cells into three distinct classes. Spinal 

 ganglia contain about 1 per cent RNA and one half 

 the lipid content of the Deiter's or Purkinje cells. 

 This considerable variation in the lipid and RNA 

 composition of different nerve cells is rather sur- 

 prising and suggests strongly the need for further 

 differentiation of neural chemistry with respect to 



