Oligodendroglia in developmental neurotoxicity.

The developing nervous system has been long recognized as a primary target for a variety of toxicants. To date, most efforts to understand the impact of neurotoxic agents on the brain have focused primarily on neurons and to a lesser degree astroglia as cellular targets. The role of oligodendroglia, the myelin-forming cells in the central nervous system (CNS), in developmental neurotoxicity has been emphasized only in recent years.

Protein kinase C activation is required for the lead-induced inhibition of proliferation and differentiation of cultured oligodendroglial progenitor cells.

Lead (Pb) is a common neurotoxicant of major public health concern. Previous studies revealed that cultured oligodendrocyte progenitor cells (OPCs) are highly vulnerable to Pb toxicity. The present study examines the effect of Pb on the survival, proliferation and differentiation of OPCs in vitro.

Lead alters the developmental profile of the galactolipid metabolic enzymes in cultured oligodendrocyte lineage cells.

Lead is a neurotoxicant that can cause myelin deficits. Galactolipids are expressed during differentiation of oligodendrocyte lineage cells and accumulate in myelin. To examine the impact of lead on oligodendroglial differentiation, galactolipid metabolism in cultured oligodendrocyte lineage cells exposed to the metal was studied.

Lead causes human fibroblasts to mis-sort arylsulfatase A.

Lead exposure causes cognitive and behavioral deficits in some children. We have proposed that the effects of single nucleotide polymorphisms (SNP) of the human pseudodeficient arylsulfatase A (ARSA) gene that result in reduced levels of the enzyme, and lead concentrations that decrease ARSA activity, culminate in cellular enzymic activity that is below a critical threshold required for the normal nervous system function. Human fibroblasts grown in the presence of lead acetate exhibit a 65% decrease in ARSA protein, resulting in a significant decrease in the ability to catabolize sulfatide in cells from individuals with the SNP(s) of pseudodeficient ARSA, but not those from subjects with the normal gene (Poretz et al.