Differential ability of astroglia and neuronal cells to accumulate lead: Dependence on cell type and on degree of differentiation

The apparent ability of astroglia to serve as a lead (Pb) sink in the matur e brain may result from either their strategic location, between the blood- brain barrier and neurons, or from intrinsic differences between the abilit y of astroglia and neurons to accumulate this metal. This phenomenon may be dependent on the degree of cell differentiation, In order to address the l atter possibility, ph accumulation was compared among the following cell cu lture models: (1) mature and immature rat astroglia, (2) undifferentiated S Y5Y human neuroblastoma cells and SY5Y cells differentiated with nerve grow th factor, (3) immature rat astroglia grown in differently conditioned medi a, some of which induce partial differentiation, and (4) rat astroglia and SY5Y cells in co-culture. Astroglial cultures, prepared from 1-day-old rat cerebral hemispheres, were exposed to 1 mu M Pb after either 14 (immature) or 21 (mature) days in culture. Pb content of the cells was measured by ato mic absorption spectroscopy. Immature astroglia took up less Pb when glutat hione (GSH) was added to the medium, suggesting that GSH may regulate Pb up take in these cells. Undifferentiated neuroblastoma cells accumulated more Pb than did the differentiated ones. Astroglia accumulated up to 24 times m ore Pb than did neuronal cells. This ability was enhanced by exposure to co nditioned medium from a neuroblastoma cell line, but not by endothelial cel l-conditioned medium, although this medium induced the expression of a glut amate-activated Ca2+ response. Our findings are in agreement with in vivo s tudies, and thus validate the use of these cell-culture models for future s tudies on differential mechanisms of Pb uptake.