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

Wenbin Deng, R. D. Poretz

Research output: Contribution to journalArticle

25 Scopus citations

Abstract

Lead poisoning is known to cause myelin defects. Galactolipids are the major lipid components of myelin and myelin-competent oligodendrocytes. The present study examines the cellular activity of enzymes involved in the galactolipid pathway, tissue concentrations of galactolipids, and the cellular activity 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 euthanized by decapitation on postnatal day 7, 14, 21, 35, or 56. Lead decreased levels of galactolipids and the oligodendrocyte marker CNPase in the brain to a similar degree. The ratios of galactocerebrosides/sulfatides and nonhydroxy fatty acid/hydroxy fatty acid forms of the galactolipids were not altered by lead treatment. In contrast, the activities of the galactolipid metabolic enzymes were reduced to a degree significantly greater than that 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 brain development by impairing timely myelin production due to perturbation of the early developmental commitment of oligodendroglial progenitors. It is further suggested that perturbation of the galactolipid pathway during the developmental maturation of oligodendrocytes may represent a contributing mechanism for Pb-induced neurotoxicity.

Original languageEnglish (US)
Pages (from-to)98-107
Number of pages10
JournalToxicology and Applied Pharmacology
Volume172
Issue number2
DOIs
StatePublished - Apr 15 2001
Externally publishedYes

Keywords

  • Arylsulfatase A
  • Galactocerebroside
  • Lead toxicity
  • Myelin
  • Oligodendrocyte
  • Sulfatide

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

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