Effects of Maternal Hyperphenylalaninemia on Postnatal Myelination in Mice

Abstract

The effects of maternal hyperphenylalaninemia induced by phenylalanine and p-chlorophenylalanine loading diets on brain growth and myelination were studied in mice. The wet weights, protein contents and activities of 2', 3'-cyclic nucleotide 3'-phosphodiesterase (CNP) of the cerebrum, brain stem and cerebellum were estimated on 7, 14, 21, 28 and 56 days after the birth. Protein and lipid contents in the myelin fraction of the whole brain were also examined on days 28 and 56. In the experimental groups, the activities of CNP, a marker enzyme of myelin, were lower than those in the control in each part of the brain. The protein contents in the light myelin subfraction, which is regarded as a mature type of myelin, were also decreased in the experimental group after 28 days of age, while those in the heavy myelin subfraction, which is regarded as an immature type of myelin, showed no significant reduction even after 28 days of age. These results suggest that maternal hyperphenylalaninemia has a potential effect on postnatal myelination of the brain, and also that impaired myelination may play some role in the pathogenesis of mental retardation of maternal phenylketonuria. The proportions of unsaturated to saturated fatty acids in phosphatidylethanolamine and sphingomyelin were decreased significantly on day 56 in the heavy myelin subfraction in compariscin to the controls. These changes may have some correlation with interference in the formation of matured myelin.