Astrocytes as mediators of methylmercury neurotoxicity: Effects on D-aspartate and serotonin uptake

V. Dave, K. J. Mullaney, S. Goderie, H. K. Kimelberg, M. Aschner

Research output: Contribution to journalArticlepeer-review

37 Scopus citations

Abstract

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 μM 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; 10μM 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.

Original languageEnglish (US)
Pages (from-to)222-231
Number of pages10
JournalDevelopmental Neuroscience
Volume16
Issue number3-4
DOIs
StatePublished - 1994
Externally publishedYes

Keywords

  • Aspartate
  • Astrocytes
  • Methylmercury
  • Neurotoxicity
  • Rat
  • Serotonin
  • Uptake

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

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