Lead exposure delays the differentiation of oligodendroglial progenitors in vitro

Lead (Pb) is an environmental neurotoxicant that can cause hypo-and demyeli nation. Oligodendrocytes (OLs), the myelin-forming cells in the central ner vous system, may be a possible target for Pb toxicity. The present study de scribes the effect of Pb on the maturation of rat OL progenitor (OP) cells and the developmental expression of myelin-specific galactolipids. Dose-res ponse studies showed that OP cultures were more sensitive to Pb than mature OLs. Pb delayed the differentiation of OL progenitors, as demonstrated by cell morphology and immunostaining with a panel of stage-specific different iation markers. Ph given prior to and during differentiation caused a decre ase in the biosynthesis of galactolipids in both undifferentiated and diffe rentiated OLs, as detected by metabolic radiolabeling with H-3-D-galactose. While the ratios of galacto/gluco-cerebrosides, hydroxy fatty acid/nonhydr oxy fatty acid galactolipids, and galactocerebrosides/sulfatides increased in control cultures during cell differentiation, Pb treatment prevented the se changes. The results suggest that chronic Pb exposure may impact brain d evelopment by interfering with the timely developmental maturation of OL pr ogenitors. (C) 2001 Academic Press.