RUTHENIUM RED NEUROTOXICITY AND INTERACTION WITH GANGLIOSIDES IN PRIMARY CORTICAL CULTURES

Ruthenium red (RR) is an inorganic polycationic dye able to exert seve ral effects on the nervous system, including neurodegeneration, both i n vivo and in cell cultures. Gangliosides hare been shown to protect c ultured neurons against several damaging conditions, and it has been p ostulated that RR can interact with the negative charges of the sialic acid residues of these molecules. In the present work we have tested the effect of the trisialoganglioside GT1b and the monosialogangliosid e GM1 on the RR-induced neuronal damage in primary cortical cultures, as well as on the binding of RR to synaptosomes. GT1b at 100-200 mu M concentrations partially protected against RR-induced neurodegeneratio n, as judged by light microscopy and by measurement of the reduction o f a tetrazolium salt, while GM1 was ineffective. GT1b, but not GM1, al so partly blocked both RR binding and its diminution in the culture me dium occurring during incubation. These results suggest that the three negative charges of GT1b enable it to interact with RR and as a conse quence the entrance of the dye into the cells is blocked and neurotoxi city is diminished, although other mechanisms of protection cannot be excluded. Endogenous polysialic acid-containing molecules do not seem to be involved in RR effects, since the removal of sialic acid residue s by treatment with neuraminidase did not prevent the cell damage. (C) 1997 Wiley-Liss, Inc.