title: Lead (Pb+2) promotes apoptosis in newborn rat cerebellar neurons: pathological implications.
abstract: Despite mandated reduction in environmental lead (Pb++), such exposure still poses a public health hazard for children, with devastating effects on CNS development. To replicate aspects of this neurotoxicity, we used cultured granule cells from newborn rat cerebella to study whether apoptotic or necrotic death is the major consequence of exposure to low micromolar concentrations of Pb++. At a low dose, 1 microM (EC50 approximately equal to 10 microM), Pb++ does not affect glutamate-induced neuronal necrosis but promotes neuronal apoptosis, as characterized morphologically by cell shrinkage and chromatin condensation, biochemically by the typical internucleosomal DNA fragmentation and functionally by dependence on new synthesis of macromolecules (cycloheximide- and actinomycin D-sensitive). The low micromolar doses of Pb++ that promote apoptosis are well within the blood level range reported to impair CNS function in children and to alter synaptogenesis in the neonatal rat brain. Thus these in-vitro results suggest that the highly neurotoxic action of Pb++ in the developing CNS of children might depend on a facilitation of apoptosis. The Pb+2-elicited potentiation of neuronal apoptosis is attenuated by treatment with the voltage-sensitive Ca+2 channel agonist Bay K8644, which suggests the possible use of this agonist for treatment of the neurotoxic effects of Pb++.
authors.affiliation: Center for Neuropharmacology and Neurochemistry, N.S. Kline Institute for Psychiatric Research, Orangeburg, New York, USA.
authors.forename: A
authors.initials: A
authors.lastname: Oberto
authors.forename: N
authors.initials: N
authors.lastname: Marks
authors.forename: H L
authors.initials: HL
authors.lastname: Evans
authors.forename: A
authors.initials: A
authors.lastname: Guidotti
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects* / Q000473:pathology; D007854:Lead / Q000633:toxicity*; D009336:Necrosis; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007854:Lead; D002118:Calcium