Protein determinants of myelination in different regions of developing rat central nervous system

Abstract

Measurements of several different protein determinants correlated with the time and rate ofmyelination in five areas of the central nervous system are pre*ented. The deposition of protein in the subcellular fraction corresponding to the density of adult myelin, the appearance of basic protein characteristic of myelin, the change in proportions of the individual myelin proteins, the appearance and distribution of the myelin marker 2':3'cyclic nucleotide 3'-phosphohydrolase, and the results ofmorphological studies ofpurified myelin axe compared. According to these various criteria, and in agreement with the morphological observations of others, myelin appears earliest in the spinal cord, then in the brain stem, and latest in the cerebral hemispheres. Multilamellarmyelin was observed in the rat brain stem and spinal cord as early as 5 days ofage. The relative proportion ofthe individual myelin proteins changed with myelin maturation in all areas, with the larger basic protein decreasing reciprocally with increase of the smaller basic protein. The proportion of Wolfgram protein also decreased with maturation. Larger proportions of the enzyme 2':3'-cyclic nucleotide 3'-phosphohydrolase were located in the microsomal fraction at early ages. During development the enzyme activity gradually became associated more with a fraction of a density corresponding to adult myelin, suggesting the presence of precursor membrane fragments in microsomal fractions in the early stages of myelination before compact myelin formation. A significant proportion of the total nucleotide phosphohydrolase activity of the homogenate could not be recovered in subcellular fraction at early ages, but the recoveries of the enzyme increased with maturation and the activity was found more in the myelin fraction. Histological examination of the developing central nervous system shows that the onset of myelin deposition occurs at different times in different regions of the central nervous system. Generaily the phylogenetically older parts of the nervous system, irrespective of species, form myelin earlier than the anterior areas. Thus myelin appears in the spinal cord first, then in the brain stem, cerebellum and forebrain. During development, biochemical changes in protein and lipid composition have been observed in myelin isolated from whole brain (