Myelination in the developing human brain: Biochemical correlates

Abstract

To delineate the biochemical sequences of myelination in the human brain, we analyzed the protein and lipid composition of white matter in 18 baseline cases ranging in age from midgestation through infancy, the critical period in human myelination when the most rapid changes occur. Three adult cases were used as indices of maturity, and 4 cases with major disorders of CNS myelination (maple syrup urine disease, severe periventricular leukomalacia, idiopathic central hypomyelination, and metachromatic leukodystrophy) were analyzed. Brain samples were obtained < or = 24 hours after death. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and high performance thin-layer chromatography were used to separate and identify proteins and polar and neutral lipids in an average of 10 sites/brain; computer-based densitometry was used to quantify polar lipids. Biochemical sequences, as manifested by the appearance of the myelin-associated lipids and myelin-specific proteins, closely followed previously described anatomic sequences both temporally and by region, and were identical in all sites sampled: sphingomyelin was followed simultaneously by cerebrosides, MBP, PLP, and nonhydroxy-sulfatide, followed by hydroxy-sulfatide. The onset and tempo of the expression of individual constituents, however, were quite variable among sites, suggesting a wide differential in vulnerable 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 of the combined biochemical approaches in pediatric brains and provides guidelines for the assessment of disorders of myelination in early human life.

DTI Values in Key White Matter Tracts from Infancy through Adolescence

“…Such studies would clearly provide novel insight into the significant differences in FA and MD values in these ROIs, thus allowing us to infer important details about white matter development, and maturation in neonates. Nonetheless, our data are consistent with several postmortem studies 19,[25][26][27][28][29] investigating the extent of myelination, which have reported that the PLIC is an "early" initiator of myelination, which begins before birth compared with other WM structures 19,[25][26][27] and that the first myelinated fibers appear in the ninth fetal month in the lenticulothalamic region, whereas myelination of the fibers in the ALIC lags behind that of the PLIC. 28,29 Our data are also consistent with previous findings 21,22,25,29,30 demonstrating an initial rapid, robust increase in WM FA and a concomitant decrease in MD in the first 24 to 36 months of life (Fig 3).…”

Late Oligodendrocyte Progenitors Coincide with the Developmental Window of Vulnerability for Human Perinatal White Matter Injury

“…Although MBP-positive myelin sheaths were detected immunohistochemically by 30 weeks, sulfatide by thin layer chromatography (TLC) and MBP by SDS-PAGE were not detected in parietal white matter until after birth (Kinney et al, 1994). The appearance of microscopic myelin does not occur until at least after the first postnatal month, and myelin tubes were not detected until 11-13 postconceptional months (Brody et al, 1987;Kinney et al, 1989).…”

White Matter Characteristics and Cognition in Prenatally Opiate- and Polysubstance-Exposed Children: A Diffusion Tensor Imaging Study

“…However, both biochemical detection of myelin-associated lipids and proteins and increases in FA are known to precede the histologic detection of myelin. 45,46 Hence, it is possible that mechanisms functioning before myelination could be affected by drug exposure in utero and ultimately affect the development of myelin. Any neurobiologic inferences based on DTI-derived measures must be made with caution.…”