Reduction of neurotoxicity of mercuric chloride and glutamate by a membrane-permeating thiol reagent in vitro

Recent evidence suggests that inorganic mercuric chloride (MC) potentiates glutamate (GLU) excitotoxicity, probably by disturbing the astrocytic GLU transport. In primary astrocytic cultures GLU transport inhibition was prevented by a cell membrane-permeating thiol (SH) reagent, dithiothreitol (DTT). In this study, excitotoxic neuronal lesions produced in an organotypic culture of rat cerebellum by combined application of individually subtoxic doses of GLU (100 mu M) and MC (1 mu M) were reduced when DTT (1 mM) was added, but not with a non-permeating SH reagent, reduced glutathione (GSH, 1 mM). The results support the view that MC neurotoxicity is mediated by its interaction with intramembraneous SH groups involved in astrocytic GLU transport.