ALTERATIONS IN THE GLIAL FIBRILLARY ACIDIC PROTEIN-CONTENT OF PRIMARYASTROCYTE CULTURES FOR EVALUATION OF GLIAL-CELL TOXICITY

Astrocyte-enriched primary glial cell cultures from the rat cerebral c ortex were exposed to a range of neurotoxic compounds and the effects on three proteins were examined by enzyme-linked immunosorbent assay ( ELISA). The most consistent marker for astrocyte toxicity was the inte rmediate filament protein glial fibrillary acidic protein (GFAp). Many toxicants reported to have specificity for astrocytes (e.g. mercuric chloride, aluminium chloride, toluene or ethanol) produced a similar d ose-response curve: increases in the GFAp content of the cells at sub- cytotoxic concentrations with attenuation at higher concentrations. So me of the concentrations required to increase GFAp were extremely low, indicating that this is a sensitive and consistent marker of cellular damage, as has been shown in vivo. Toxicants that have neuronal speci ficity (such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridinium or acry lamide) had no effects on GFAp levels, indicating that the system meas ures the susceptibility of astrocytes to specific toxicants rather tha n neurotoxicity. The levels of S-100 protein and vimentin were measure d for a smaller number of toxicants. S100 was a less sensitive and inc onsistent marker in comparison with GFAp, whilst vimentin levels were not seen to increase with any tested compound. These results suggest t hat astrocytes have a valuable place in culture models for neurotoxici ty testing.