Lead toxicity in primary cultured cerebral astrocytes and cerebellar granular neurons

Neurons are more sensitive than astrocytes to lead toxicity in vivo. In order to understand the bases for the differences in brain cell responses to lead, the effects of lead acetate on cell morphology and on aerobic energy metabolism were studied in rat primary cultured neurons and astrocytes. By transmission electron microscopy, neuronal cell damage was seen with exposure to lead concentrations which were much lower than those required for similar changes in the astrocyte. As previously described in our studies of in vivo lead exposure, astrocytes in primary culture concentrated lead in nuclear, cytoplasmic, and lysosomal inclusions while neurons showed lead densities only in lysosomes. With acute lead exposures, inhibition of maximal respiratory capacity was greater and occurred at lower lead concentrations in neurons than in astrocytes. Similarly, respiratory rates were inhibited at lower lead concentrations in cerebral cortical slices from 8-day-old rat pups compared to those from adults. We conclude that primary cultured brain cells are appropriate in vitro systems for studying the in vivo cellular responses to lead. As in vivo, neurons are more sensitive than astrocytes to lead toxicity. In both cells, inhibition of aerobic energy metabolism appears to be closely associated with cell damage. The capacity of the astrocyte to sequester lead in nonmitochondrial intracellular sites may be critical in resistance to lead toxicity in vitro and in the mature brain.