Neurotoxic effects of aluminium on embryonic chick brain cultures.
Toxic damage of brain cells by aluminium (Al) is discussed as a possible factor in the development of neurodegenerative disorders in humans. To investigate neurotoxic effects of Al, serum-free cultures of mechanically dissociated embryonic chick (stage 28-29) forebrain, brain stem and optic tectum, and for comparison meningeal cells, were treated with Al (0-1000 microM) for 7 days. Effects of Al on cell viability (lysosomal and mitochondrial activity) and differentiation (synthesis of cell-specific proteins) were found to the brain area specific with the highest sensitivity observed in optic tectum. No inhibiting effects on cell viability could be observed in cultures of forebrain and meninges in the concentration range tested. In all three brain tissue cultures, threshold levels for the reduction of cell differentiation parameters were found at lower concentrations [concentration resulting in a 50% decrease (IC50) > 180 microM] than for the inhibition of cell viability (IC50 > 280 microM), indicating a specific toxic potential of Al for cytoskeletal alterations. The culture levels of nerve cell-specific markers microtubule-associated protein type 2 (the most sensitive parameter) and the 68-kDa neurofilament were inhibited at lower concentrations (IC50 180-630 microM) than the astrocyte-specific glial fibrillary acidic protein (IC50 700-approximately 1000 microM), demonstrating a particularly high sensitivity of neurons in comparison to astrocytes. Based on these differences in Al sensitivity observed for different cell markers in the various brain tissue cultures, the in vitro system used in the present study proved to be a suitable model to assess brain area and cell type-specific neurotoxic effects of Al.
Institute of Toxicology, ETH and University of Zürich, Switzerland.
J P
JP
Müller
A
A
Bruinink
D000535:Aluminum / Q000633:toxicity*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000196:embryology; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002642:Chick Embryo; D004797:Enzyme-Linked Immunosorbent Assay; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis; D016900:Neurofilament Proteins / Q000096:biosynthesis; D009474:Neurons / Q000187:drug effects*
D005904:Glial Fibrillary Acidic Protein; D008869:Microtubule-Associated Proteins; D016900:Neurofilament Proteins; C066858:neurofilament protein NF 68; D000535:Aluminum