Neurotoxic effects of aluminium on embryonic chick brain cultures

Toxic damage of brain cells by aluminium (A1) is discussed as a possible factor in the development of neurodegenerative disorders in humans. To investigate neurotoxic effects of A1, 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 A1 (0–1000 M) for 7 days. Effects of A1 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 M] than for the inhibitionof cell viability (IC₅₀>280 M) indicating a specific toxic potential of A1 for cytoskeletal alterations. The culture levels of nerve cellspecific markers microtubule-associated protein type 2 (the most sensitive parameter) and the 68-kDa neurofilament were inhibited at lower concentrations (IC₅₀ 180–630 M) than the astrocyte-specific glial fibrillary acidic protein (IC₅₀ 700–1000 M), demonstrating a particularly high sensitivity of neurons in comparison to astrocytes. Based on these differences in A1 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 A1.This study is part of the Ph. D. thesis of Judith P. Mueller.Preliminary results were presented at the 24th Annual Meeting of the Swiss Societies for Experimental Biology (USGEB/USSBE)