Dave V, Mullaney K J, Goderie S, Kimelberg H K, Aschner M
Department of Pharmacology and Toxicology, Albany Medical College, N.Y.
Dev Neurosci. 1994;16(3-4):222-31. doi: 10.1159/000112110.
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.
在本研究中，我们探讨了优先蓄积于星形胶质细胞中的金属氯化甲基汞（MeHgCl）对大鼠原代星形胶质细胞培养物摄取5-羟色胺（5-HT）和谷氨酸/天冬氨酸的影响。在7日龄和21日龄的原代星形胶质细胞培养物中，进行了定量放射自显影（ARG）结合胶质酸性纤维蛋白（GFAP）免疫细胞化学，以及对这些神经递质放射性标记摄取的完整细胞（总体）测量。用MeHg（10微摩尔，处理30分钟）处理星形胶质细胞（培养21天）显著抑制了Na⁺依赖性且对氟西汀敏感的[³H]5-HT摄取。7日龄和21日龄培养物中的D-天冬氨酸摄取对MeHg更为敏感，导致星形胶质细胞对D-天冬氨酸的摄取受到>99%的抑制（30分钟；10微摩尔MeHg）。这些结果表明，原代星形胶质细胞培养物中Na⁺依赖性且对氟西汀敏感的5-HT摄取，以及Na⁺依赖性L-谷氨酸/D-天冬氨酸摄取系统对低浓度的MeHg敏感。由于星形胶质细胞在原位从细胞外空间清除谷氨酸（和天冬氨酸）以及5-HT对于维持化学稳态至关重要，MeHg诱导的5-HT和天冬氨酸摄取抑制可能对邻近神经元产生细胞毒性作用。
