Glial cells contribute more to iron and aluminum accumulation but are moreresistant to oxidative stress than neuronal cells

Iron (Fe) and aluminum (Al) have been implicated in the pathogenesis of Alz heimer's disease (AD). In this study, we examined neuronal and glial cells to clarify which contributes most to metal accumulation after internalizati on through the transferrin-independent iron uptake (Tf-IU) systems in prima ry neuronal and glial predominant (NP and GP) cells from rat cerebral corte x, which affect the accumulation of transition metals in a variety of cultu red cells. Al more significantly upregulated the Tf-IU activity in GP cells than in NP cells. GP cells were more resistant to Fe and Al exposure than NP cells. However, a chemiluminescence analysis specific for reactive oxyge n species (ROS) showed that ROS levels in Fe- or Al-loaded NP cells were tw ice as high as in Fe- or Al-loaded GP cells. Northern blot analysis and gel retardation assay showed that the Al and Fe exposure taken up by the cells suppress Tf receptor mRNA expression to a greater extent in GP than NP cel ls, indicating that Al and Fe more markedly accumulate in glial than in neu ronal cells. These results suggest that glial cells rather than neuronal ce lls contribute to the metal accumulation and are more resistant to oxidativ e stress caused by metals than neuronal cells. The present study may help t o explain the pathogenesis of neurodegeneration in AD disorders caused by m etal-generated oxidative stress. (C) 2000 Elsevier Science B.V. All rights reserved.