Abstract
The development of the human brain during normal growth between 13 weeks' gestation and 26 months postpartum was studied. The effect of protein-energy malnutrition during the first 2 years of life on this developmental process was also investigated. DNA, protein, polyamines and putrescine, cholesterol esters, phospholipids and gangliosides were measured in three major parts of the brain, namely the forebrain, cerebellum and brain stem. Two phases of rapid brain growth were observed, the first between 13 and 20 weeks' gestation and the other between 30 gestational weeks and 9 months of age. During the first phase, the total amount of DNA increased relatively more rapidly, and so did the concentrations of putrescine, gangliosides and phospholipids. At all ages examined, the concentration of putrescine was much higher than that of either of the polyamines. The second phase was the period of most accretion of putrescine and the lipids. During development, choline phosphoglycerides decreased in proportion while sphingomyelin and ethanolamine phosphoglycerides increased, and this pattern was found in all three parts of the brain. In contrast, the ganglioside pattern was different in different parts, with G D1a as the major ganglioside in the forebrain and brain stem, and G[T1] as the major ganglioside in the cerebellum. The concentration of cholesterol esters fell during development; however, there was a transient rise at around the time of birth. In the brain of the malnourished children, the concentration of sphingomyelin was lower and that of the cholesterol esters higher than normal. The fatty acid composition of the cholesterol esters was different from that found in the brain of the well-nourished children. Study of gangliosides of the developing brain of the rat showed that in this species also, the major gangliosides in the forebrain and cerebellum were G[D1a] and G[T1], respectively, but G D1b was the most predominant fraction in the brain stem. Undernutrition before and after birth resulted in a higher concentration of gangliosides in all three parts of the brain at 21 days of age; however, the concentration was lower than normal at later ages. Subcellular fractionation of the forebrain showed that chronic undemutrition caused a retention of the disialogangliosides, G[D1a] and G[D1b], in myelin, which normally disappear during brain maturation. Labelling of the brain gangliosides by intraperitoneal administration of D-[1-[3]H]-glucosamine has shown that the of myelin in the undernourished rats had a faster than normal rate of turn-over. It is suggested that malnutrition in early life in the human, or chronic undernutrition in the rat may result in the formation of myelin which is chemically and, so presumably, functionally, immature for age.