MYELINATION IN THE DEVELOPING HUMAN BRAIN - BIOCHEMICAL CORRELATES

To delineate the biochemical sequences of myelination in the human bra in, we analyzed the protein and lipid composition of white matter in 1 8 baseline cases ranging in age from midgestation through infancy, the critical period in human myelination when the most rapid changes occu r. Three adult cases were used as indices of maturity, and 4 cases wit h major disorders of CNS myelination (maple syrup urine disease, sever e periventricular leukomalacia, idiopathic central hypomyelination, an d metachromatic leukodystrophy) were analyzed. Brain samples were obta ined less than or equal to 24 hours after death. Sodium dodecyl sulfat e-polyacrylamide gel electrophoresis and high performance thin-layer c hromatography were used to separate and identify proteins and polar an d neutral lipids in an average of 10 sites/brain; computer-based densi tometry was used to quantify polar lipids. Biochemical sequences, as m anifested by the appearance of the myelin-associated lipids and myelin -specific proteins, closely followed previously described anatomic seq uences both temporally and by region, and were identical in all sites sampled: sphingomyelin was followed simultaneously by cerebrosides, MB P, PLP, and nonhydroxy-sulfatide, followed by hydroxy-sulfatide. The o nset and tempo of the expression of individual constituents, however, were quite variable among sites, suggesting a wide differential in vul nerable periods to insult in biochemically-specific pathways in early life. Cholesterol ester was transiently elevated during late gestation and early infancy, prior to and around the time of the appearance of cerebrosides, sulfatides, PLP, and MBP. Distinctive lipid and protein abnormalities were detected in idiopathic central hypomyelination and metachromatic leukodystrophy. This study underscores the feasibility o f the combined biochemical approaches in pediatric brains and provides guidelines for the assessment of disorders of myelination in early hu man life.