Myelin synthesis during postnatal nutritional deprivation and subsequent rehabilitation

Abstract

Newborn Long-Evans rats were undernourished by maternal deprivation so that by 20 days of age their body and brain weights were about 45 and 80%, respectively, of the values obtained for control (well-nourished) values. Proteins from myelin of undernourished and control rats were separated by polyacrylamide gel electrophoresis in buffers containing sodium dodecyl sulfate. At 15 and 20 days of age the proportion of basic and proteolipid protein was reduced in the starved animals relative to controls, indicative of a delay in maturation. However, by 30 days of age the composition of myelin from starved and control animals appeared similar. At all ages the yield of myelin from brains of starved rats was less than 25% of that obtained from control animals. A series of isotope labeling experiments, using a double label design, was carried out to compare relative rates of incorporation of radioactive amino acids into individual proteins of various brain subcellular fractions. In 20-day-old rats the incorporation of [3H] OR [14C] leucine or glycine into myelin proteins, relative to incorporation into proteins of other subcellular fractions, is preferentially depressed (about 60%) in starved animals. Synthesis of all the myelin proteins was depressed, supporting the hypothesis that the high molecular weight proteins isolated with myelin are true myelin constituents. Similar experiments were conducted using [3H]-and [14C] acetate, choline, or glycerol as precursors of lipids. Incorporation of isotope into lipids of myelin, relative to lipids of other subcellular fractions, was also depressed by about 60% in starved animals. In several experiments we studied synthesis during rehabilitation (ad libitum feeding) following 20 days of postnatal starvation. After 6 days of rehabilitation, incorporation of radioactive precursors into myelin, relative to other subcellular fractions, was still depressed. This result was true for both proteins and lipids, and was interpreted as evicence against the initiation of a process leading to a net recovery of myelin (i.e., an irreversible deficit of myelin synthesis is induced by this regime of nutritional deprivation).