Effect of Intrauterine Growth Retardation on the Biochemical Maturation of Brain Synaptosomes in the Rat

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Abstract
The pattern of synaptosomal biochemical composition that accompanies brain maturation in rats, and the changes produced in this pattern during the experimental induction of intrauterine growth retardation by the ligation of the vessels of one uterine horn on day 15 of pregnancy (Wigglesworth method) were studied. Synaptosomes were isolated by centrifugation in a discontinuous sucrose gradient. Preparations were at least 80% pure, based on evaluation with an electron microscope. The brain weight/body weight ratio increased during the first 15 days of life and then decreased until adulthood. Both protein/DNA and the RNA/DNA ratios increased progressively from birth to adulthood. The highest rate of increase for both ratios was between days 8 and 15 of life. Brain from intrauterine growth-retarded rats had a lower RNA/DNA ratio, a parameter that can be roughly equated with cell functionality, than that from the normal newborns. The protein/DNA ratio in the former was significantly larger than that in the full-term newborn animals. On the other hand, both synaptosomal number in total brain (mg synaptosomal protein/brain weight) and synaptosomal RNA/total brain DNA were lower in the intrauterine growth-retarded animal. During synaptosomal maturation, cephalin and lecithin concentrations remained unchanged while sphingomyelin and cardiolipin showed a steady increase. In the synaptosomes of the intrauterine growth-retarded rats sphingomyelin and cephalin concentrations were significantly lower while cardiolipin was higher than in full-term animals. Gamma aminobutyric acid concentration was 3 times higher in the synaptosomes of growth-retarded than in normal newborn rats (41 ± 4.3 versus 12 ± 2.4 nmoles/mg protein).