Yan J, Studer L, McKay R D
Laboratory of Molecular Biology, NINDS, NIH, Bethesda, MD, USA.
J Neurochem. 2001 Jan;76(1):307-11. doi: 10.1046/j.1471-4159.2001.00073.x.
CNS precursors derived from E12 rat mesencephalon proliferate in the presence of basic fibroblast growth factor and differentiate in vitro into functional dopaminergic neurons, which upon transplantation alleviate behavioral symptoms in a rat model of Parkinson's disease. Here we show that the efficiency of dopaminergic differentiation decreases in the mesencephalic precursors that were proliferated or passaged for extended periods in vitro. Ascorbic acid treatment restored dopaminergic differentiation in these precursors and led to a greater than 10-fold increase in dopamine neuron yield compared with untreated cultures. The effect of ascorbic acid was stereospecific and could not be mimicked by any other antioxidants. The expression of sodium-dependent vitamin C transporter, a recently identified stereospecific ascorbic acid transporter, was maintained in mesencephalic precursors for extended in vitro periods. Pre-treatment of in vitro expanded mesencephalic precursors with ascorbic acid might facilitate the large-scale generation of dopaminergic neurons for clinical transplantation.
源自E12大鼠中脑的中枢神经系统前体细胞在碱性成纤维细胞生长因子存在的情况下增殖，并在体外分化为功能性多巴胺能神经元，移植后可缓解帕金森病大鼠模型的行为症状。我们在此表明，在体外长时间增殖或传代的中脑前体细胞中，多巴胺能分化效率降低。抗坏血酸处理可恢复这些前体细胞中的多巴胺能分化，并导致多巴胺神经元产量比未处理的培养物增加10倍以上。抗坏血酸的作用具有立体特异性，任何其他抗氧化剂都无法模拟。钠依赖性维生素C转运体是最近发现的一种立体特异性抗坏血酸转运体，其表达在中脑前体细胞中可在体外长时间维持。用抗坏血酸对体外扩增的中脑前体细胞进行预处理可能有助于大规模生成用于临床移植的多巴胺能神经元。
