Lead exposure delays the differentiation of oligodendroglial progenitors in vitro.
Lead (Pb) is an environmental neurotoxicant that can cause hypo- and demyelination. Oligodendrocytes (OLs), the myelin-forming cells in the central nervous system, may be a possible target for Pb toxicity. The present study describes the effect of Pb on the maturation of rat OL progenitor (OP) cells and the developmental expression of myelin-specific galactolipids. Dose-response 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 differentiation markers. Pb given prior to and during differentiation caused a decrease in the biosynthesis of galactolipids in both undifferentiated and differentiated OLs, as detected by metabolic radiolabeling with 3H-D-galactose. While the ratios of galacto/gluco-cerebrosides, hydroxy fatty acid/nonhydroxy fatty acid galactolipids, and galactocerebrosides/sulfatides increased in control cultures during cell differentiation, Pb treatment prevented these changes. The results suggest that chronic Pb exposure may impact brain development by interfering with the timely developmental maturation of OL progenitors.
Deng
W
W
Department of Biochemistry and Microbiology, Rutgers University, 76 Lipman Drive, New Brunswick, New Jersey 08901, USA.
McKinnon
R D
RD
Poretz
R D
RD
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects; D005455:Fluorescent Antibody Technique; D005699:Galactosylceramides / Q000032:analysis / Q000096:biosynthesis; D005732:Gangliosides / Q000032:analysis; D005963:Glucosylceramides / Q000032:analysis / Q000096:biosynthesis; D007854:Lead / Q000633:toxicity*; D008858:Microscopy, Phase-Contrast; D009836:Oligodendroglia / Q000187:drug effects* / Q000502:physiology; D009942:Organometallic Compounds / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000187:drug effects* / Q000502:physiology; D013433:Sulfoglycosphingolipids / Q000032:analysis; D014316:Tritium
D005699:Galactosylceramides; D005732:Gangliosides; D005963:Glucosylceramides; D009942:Organometallic Compounds; D013433:Sulfoglycosphingolipids; C002454:galactocerebroside; C062875:ganglioside A2B5; D014316:Tritium; D007854:Lead; C008261:lead acetate