Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human neural progenitor cells: A combined study of metabolomics and morphological analysis
Effect of low-dose thalidomide on dopaminergic neuronal differentiation of human neural progenitor cells: A combined study of metabolomics and morphological analysis
复制标题
DOI：
10.1016/j.neuro.2012.08.016
复制
发表时间：
2012-10-01
期刊：
影响因子：
3.4
通讯作者：
Sone, Hideko
中科院分区：
文献类型：
--
作者：
Qin, Xian-Yang;Akanuma, Hiromi;Sone, Hideko
沙利度胺越来越多地用于抗癌和抗炎治疗。然而，它以其致畸性和诱发周围神经病变的能力而闻名，尽管其对人类神经影响的潜在机制尚不清楚。在本研究中，我们研究了沙利度胺对人神经前体细胞代谢和神经分化的影响。我们发现，沙利度胺治疗后，与多巴胺和蛋氨酸代谢有关的酪氨酸、苯丙氨酸、蛋氨酸和谷胱甘肽水平降低。形态学分析显示，与对照组相比，100 NM沙利度胺处理后，多巴胺能(酪氨酸羟基酶阳性)神经元的数量显著减少。我们的结果表明，在使用沙利度胺治疗神经退行性疾病和其他疾病之前，应该考虑到这些不良的神经影响。(C)2012 Elsevier Inc.保留所有权利。
Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100 nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases. (C) 2012 Elsevier Inc. All rights reserved.