Astrocytes as mediators of methylmercury neurotoxicity: effects on D-aspartate and serotonin uptake.
In this study we address the effects of methylmercuric chloride (MeHgCl), a metal that is preferentially sequestered in astrocytes, on 5-HT and glutamate/aspartate uptake by rat primary astrocyte cultures. Quantitative autoradiography (ARG) combined with glial acidic fibrillary protein (GFAP) immunocytochemistry, as well as intact-cell (bulk) measurements of radiolabel uptake of these neurotransmitters were performed in 7- and 21-day-old primary astrocyte cultures. MeHg (10 microM for 30 min) treatment of astrocytes (21 days in culture) significantly inhibited the Na(+)-dependent and fluoxetine-sensitive [3H]5-HT uptake. D-aspartate uptake in 7- and 21-day-old cultures was even more sensitive to MeHg, leading to > 99% inhibition of D-aspartate uptake by astrocytes (30 min; 10 microM MeHg). These results imply that the Na(+)-dependent and fluoxetine-sensitive 5-HT uptake, as well as the Na(+)-dependent L-glutamate/D-aspartate uptake systems in primary astrocyte cultures are sensitive to low concentrations of MeHg. Since astrocytic removal of glutamate (and aspartate) and 5-HT from the extracellular space in situ is crucial to the maintenance of chemical homeostasis, MeHg-induced uptake inhibition of 5-HT and aspartate could have cytotoxic effects on neighboring neurons.
Dave
V
V
Department of Pharmacology and Toxicology, Albany Medical College, N.Y.
Mullaney
K J
KJ
Goderie
S
S
Kimelberg
H K
HK
Aschner
M
M
D000818:Animals; D000831:Animals, Newborn; D001224:Aspartic Acid / Q000378:metabolism*; D001253:Astrocytes / Q000502:physiology*; D001345:Autoradiography; D002478:Cells, Cultured; D005473:Fluoxetine / Q000494:pharmacology; D007150:Immunohistochemistry; D008767:Methylmercury Compounds / Q000633:toxicity*; D009422:Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012964:Sodium / Q000502:physiology
D008767:Methylmercury Compounds; D005473:Fluoxetine; D001224:Aspartic Acid; D012701:Serotonin; D012964:Sodium