ASTROCYTES AS MEDIATORS OF METHYLMERCURY NEUROTOXICITY - EFFECTS ON D-ASPARTATE AND SEROTONIN UPTAKE

In this study we address the effects of methylmercuric chloride (MeHgC l), a metal that is preferentially sequestered in astrocytes, on 5-HT and glutamate/aspartate uptake by rat primary astrocyte cultures. Quan titative autoradiography (ARG) combined with glial acidic fibrillary p rotein (GFAP) immunocytochemistry, as well as intact-cell (bulk) measu rements of radiolabel uptake of these neurotransmitters were performed in 7- and 21-day-old primary astrocyte cultures. MeHg (10 mu M for 30 min) treatment of astrocytes (21 days in culture) significantly inhib ited the Na+-dependent and fluoxetine-sensitive [H-3]5-HT uptake. D-as partate uptake in 7- and 21-day-old cultures was even more sensitive t o MeHg, leading to > 99% inhibition of D-aspartate uptake by astrocyte s (30 min; 10 mu M MeHg). These results imply that the Na+-dependent a nd fluoxetine-sensitive 5-HT uptake, as well as the Na+-dependent L-gl utamate/D-aspartate uptake systems in primary astrocyte cultures are s ensitive to low concentrations of MeHg. Since astrocytic removal ;of g lutamate (and aspartate) and 5-HT from the extracellular space in situ is crucial to the maintenance of chemical homeostasis, MeHg-induced u ptake inhibition of 5-HT and aspartate could have cytotoxic effects on neighboring neurons.