O. Sorg et al., INCREASED VULNERABILITY OF NEURONS AND GLIAL-CELLS TO LOW CONCENTRATIONS OF METHYLMERCURY IN A PROOXIDANT SITUATION, Acta Neuropathologica, 96(6), 1998, pp. 621-627
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.