Effects of lead treatment on intracellular iron and copper concentrations in cultured astroglia

Astroglia are implicated in the pathogenesis of lead (Pb) neurotoxicity in two capacities: as a lead sink that sequesters lead and as a target for direct cellular damage. A proposed cellular mechanism of Pb neurotoxicity is the alteration of metal concentrations, particularly the intracellular accumulation of Cu2+. We measured Pb uptake and the effects of Pb acetate on intracellular trace metal concentrations in astroglial cultures prepared from 0- to 4-day-old rat cerebral hemispheres. Mature Sprague Dawley and immature Wistar rat astroglia in culture took up lead from the medium. This finding replicates in vitro the finding reported by others that astroglia in the brain take up Pb. Intracellular Cu and Fe concentrations (micrograms per 2 x 10(6) cells) were increased fourfold or more by treatment with 100 microM Pb for 3 days in the cultures of immature astroglia. Cu levels were also increased twofold or more in mature astroglia treated for 1-3 days with 100 microM Pb. The significance of this finding is that Cu is a potent inhibitor of Na+, K+-ATPase, an enzyme by which astroglia are thought to remove K+ from the extracellular fluid in the brain. Thus, this finding supports the hypothesis that elevated [Cu], and perhaps [Fe], is a subcellular mechanism of neurotoxicity.