Myelinogenesis in the Rat Brain

Abstract

MORPHOLOGICAL evidence indicates that myelin is formed in the central nervous system by the wrapping of macroglial plasma membrane about the axon^1,2. Proliferation of glial cells occurs shortly before myelination³, and connecting processes between oligodendrocytes and the developing myelin sheath have been noted⁴. This concept is supported by experiments with isotopes, which suggest that lipid from the microsomal fraction, which would include glial plasma membrane, is utilized in myelin formation⁵. Myelin would therefore be expected to have the same or similar chemical composition as that of the oligodendroglial plasma membrane and myelin lipids would be present in the brain during the stage of glial proliferation immediately before the first appearance of myelin rings. Analysis of glial-rich fractions from adult rat brain (Table 1), however, shows that they contain much less cerebroside and more phospholipid than is present in myelin, and hence that the composition is similar to that of most other tissue membrane systems. This same type of lipid composition is found in glial tumour tissue (Table 2) and in the glial-rich brain just before the onset of myelination⁹. In order to examine the sequence of biochemical events further, myelin has been isolated from the brains of rats from 10 days old onwards. The early myelin fraction was found to have a low cerebroside content and to be rich in phospholipid and thus similar to the lipid composition of glia (Table 1). Only when rats were 30 days old was the adult myelin lipid ratio attained. Morphological, enzyme and chemical examination of myelin from 12 day old rats does not suggest that this fraction is heavily contaminated by other subcellular fractions. Thus little succinic dehydrogenase and ATPase activity and only small amounts of nucleic acids are found in the preparation. It therefore seems possible that early myelin consists essentially of oligodendroglial plasma membrane and that later insertion of cerebroside into the myelin lamella produces the stable mature membrane structure. This hypothesis, which attributes a key role to cerebroside, may be pertinent to neurological diseases in which defects in cerebroside content have been noted.