Lead exposure affects levels of galactolipid metabolic enzymes in the developing rat brain

Lead poisoning is known to cause myelin defects. Galactolipids are the majo r lipid components of myelin and myelin-competent oligodendrocytes, The pre sent study examines the cellular activity of enzymes involved in the galact olipid pathway, tissue concentrations of galactolipids, and the cellular ac tivity of 2 ' ,3 ' -cyclic nucleotide 3 ' -phosphohydrolase (CNPase) in rat pups exposed to lead in utero and subsequently through maternal milk from exposed mothers and in drinking water following weaning. Pups from control and lead-treated groups (500 or 2000 ppm lead in the drinking water) were e uthanized by decapitation on postnatal day 7, 14, 21, 35, or 56, Lead decre ased levels of galactolipids and the oligodendrocyte marker CNPase in the b rain to a similar degree, The ratios of galactocerebrosides/sulfatides and nonhydroxy fatty acid/hydroxy fatty acid forms of the galactolipids were no t altered by lead treatment, In contrast, the activities of the galactolipi d metabolic enzymes were reduced to a degree significantly greater than tha t of CNPase or galactolipids. These results are consistent with previously obtained data indicating that in vitro cultured oligodendroglial progenitor cells are a target for Pb toxicity. Chronic Pb exposure may impact on brai n development by impairing timely myelin production due to perturbation of the early developmental commitment of oligodendroglial progenitors, It is f urther suggested that perturbation of the galactolipid pathway during the d evelopmental maturation of oligodendrocytes may represent a contributing me chanism for Pb-induced neurotoxicity, (C) 2001 Academic Press.