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首页> 外文期刊>The European Journal of Neuroscience >5-Bromo-2'-deoxyuridine is selectively toxic to neuronal precursors in vitro.
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5-Bromo-2'-deoxyuridine is selectively toxic to neuronal precursors in vitro.

机译：5-Bromo-2'-deoxyuridine在体外对神经元前体有选择性毒性。

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摘要

The effect of 5-bromo-2'-deoxyuridine (BrdU) incorporation on the phenotype of progeny derived from expanded E18 rat striatal precursors was examined. BrdU was administered to cultures for 24 h prior to differentiation. Results revealed that there was selective toxicity of this compound to developing TuJ1+ neurons, but not glia, at concentrations used in most labelling studies. Therefore, a BrdU dose-response curve from 0.2 microM to 10 microM was established. The optimum dose of BrdU for labelling cells was 0.2 microM, well below the 1-10 microm recommended concentration. This dose resulted in the survival of significantly more newborn BrdU/TuJ1+ double-labelled neurons and eliminated the toxic effects of BrdU. Administration of 10 microm BrdU resulted in a significant decrease in extracellular regulated kinase (ERK) phosphorylation compared with untreated cultures, this could be completely restored by the administration of either N-methyl-D-aspartate (NMDA) receptor antagonists such as MK801 or the nitric oxide synthesis inhibitor L-methyl-arginine methyl ester (L-NAME). Our results show that high levels of BrdU are selectively toxic to neurons through a mechanism that activates classical cell death pathways. This has implications for labelling studies both in vivo and in vitro.
机译：检查了5-溴-2'-脱氧尿苷（BrdU）掺入对衍生自扩展的E18大鼠纹状体前体的后代表型的影响。分化前将BrdU给予培养物24小时。结果显示，在大多数标记研究中使用的浓度下，该化合物对正在发育的TuJ1 +神经元具有选择性毒性，但对胶质细胞没有毒性。因此，建立了从0.2 microM到10 microM的BrdU剂量反应曲线。用于标记细胞的BrdU的最佳剂量为0.2 microM，远低于建议的1-10 microm浓度。该剂量导致更多的新生儿BrdU / TuJ1 +双标记神经元存活，并消除了BrdU的毒性作用。与未处理的培养物相比，施用10微米BrdU导致细胞外调节激酶（ERK）磷酸化显着降低，这可以通过施用N-甲基-D-天冬氨酸（NMDA）受体拮抗剂（例如MK801或一氧化氮合成抑制剂L-甲基-精氨酸甲酯（L-NAME）。我们的结果表明，高水平的BrdU通过激活经典细胞死亡途径的机制对神经元具有选择性毒性。这对体内和体外的标记研究都有影响。

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