INCREASED VULNERABILITY OF NEURONS AND GLIAL-CELLS TO LOW CONCENTRATIONS OF METHYLMERCURY IN A PROOXIDANT SITUATION

Using reaggregating rat brain cell cultures at two different stages of differentiation, we examined the biochemical effects of a 10-day trea tment with nanomolar concentrations of methylmercuric chloride (monome thylmercury), in the presence or absence of promoters of hydroxyl radi cal formation (10 mu M copper sulphate plus 100 mu M ascorbate). A dec rease in total protein content accounted for the general cytotoxicity of these compounds, whereas selective effects were assessed by determi ning the activities of cell type-specific enzymes. Methylmercury, up t o 100 nM, as well as the copper ascorbate mixture, when applied separa tely, induced no general cytotoxicity, and only slight effects on neur onal parameters. However, when applying 100 nM methylmercury and the c opper-ascorbate mixture together, a drastic decrease in neuronal and g lial parameters was found. Under these conditions, the content of reac tive oxygen species, assessed by 2',7'-dichlorofluorescin oxidation, i ncreased greatly, while the activities of antioxidant enzymes decrease d. In the presence of copper and ascorbate, differentiated cultures ap peared more resistant than immature ones to low methylmercury concentr ations (1-10 mM), but did undergo similar changes in both cell type-sp ecific and antioxidant enzyme activities at 100 nM methylmercury. Thes e results suggest that in prooxidant conditions low doses of mercury c an become much more deleterious for the central nervous system.