Aluminum-induced degeneration of astrocytes occurs via apoptosis and results in neuronal death

The mechanisms by which aluminum interacts with the nervous system are only partly understood. In this study, we used cultured astrocytes and neurons to investigate the effects of long exposures to aluminum(1 mM). We found th at aluminum accumulated both in neurons and astrocytes, After 8-12 days exp osure, aluminum caused strong changes in the morphology of astrocytes inclu ding shrinkage of cell bodies and retraction of processes. Exposures over 1 5-18 days reduced astrocytes viability by 50%. Aluminum-induced degeneratio n of astrocytes involved the DNA fragmentation characteristic of apoptosis, and staining of aluminum-treated astrocytes with the DNA-binding fluorochr ome Hoeschst 33258 revealed the typical apoptotic condensation and fragment ation of chromatin. Aluminum was also found to be neurotoxic, causing first (4-6 days) abnormal clustering and aggregation, and later (8-12 days) neur onal death. Interestingly, aluminum neurotoxicity occurred in neuroglial cu ltures containing approximately 10% astrocytes but not in near-pure neurona l cultures containing only 1% astrocytes. Staining of co-cultured cells wit h Hoeschst 33258 showed apoptotic condensation and fragmentation of chromat in in aluminum-treated astrocytes but not in co-cultured neurons. Our study demonstrates that aluminum can induce the apoptotic degeneration of astroc ytes, and that this toxicity is critical in determining neuronal degenerati on and death. Aluminum-mediated apoptosis of cultured astrocytes may be als o a valuable model system to study the mechanisms underlying apoptosis in g lial cells. (C) 1999 Elsevier Science B.V. All rights reserved.