Comparison of alterations in amino acids content in cultured astrocytes or neurons exposed to methylmercury separately or in co-culture.
Methylmercury (MeHg) is an environmental toxicant that induces enduring neuropsychological deficits in humans. Although the mechanisms associated with MeHg-induced neurotoxicity have not yet been fully elucidated, some lines of evidence point out to excitatory amino acids dyshomeostasis as an important outcome of MeHg exposure. The present study was designed to characterize the effects of MeHg on amino acid content in co-cultured astrocytes and neurons or in each cell type under solitary conditions. The results showed that glutamate concentrations significantly decreased in neurons, but not in astrocyte cultures exposed to 10 microM MeHg. The decrease in neurons was fully reversed when these cells were co-cultured with astrocytes. The content of other amino acids (aspartate, alanine, glycine and serine) decreased upon exposure to 10 microM MeHg in both neurons and astrocytes cultured in solitary conditions, although the effect was generally smaller in astrocytes than in neurons. However, the content of these amino acids in each of the cell types was indistinguishable from controls when co-cultures were treated with MeHg. Overall, the results indicate that astrocytes, which are more resistant to amino acid modulation by MeHg, can (i) mitigate the effects of MeHg that occur in neurons cultured in solitary conditions and (ii) become themselves more MeHg resistant in the presence of neurons. Delineating the mechanisms underlying the mutual neuroprotective effects of astrocytes and neurons in co-culture to MeHg-induced amino acid imbalance requires further investigation.
Department of Pediatrics, and the Kennedy Center for Research on Human Development, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
Zhaobao
Z
Yin
Jan
J
Albrecht
Tore
T
Syversen
Haiyan
H
Jiang
Marshall
M
Summar
Joao B T
JB
Rocha
Marcelo
M
Farina
Michael
M
Aschner
D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D008767:Methylmercury Compounds / Q000633:toxicity*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D008767:Methylmercury Compounds