Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells

Estrogen promotes differentiation and survival of dopaminergic neurons derived from human neural stem cells
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DOI:
10.1002/jnr.20362
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发表时间:
2005-02-01
影响因子:
4.2
通讯作者:
Hashimoto, N
Hashimoto, N
中科院分区:
医学3区
文献类型:
--
作者:
Kishi, Y;Takahashi, J;Hashimoto, N

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为了研究雌激素对神经元分化的影响,特别是对多巴胺能(DA)神经元的影响,在17 β-雌二醇的存在下分化人神经干细胞(NSCs)。体外培养的神经干细胞中出现酪氨酸羟化酶(TH)阳性神经元,其比例随雌二醇浓度的增加而增加。TH阳性神经元的增加被雌激素受体(ER)拮抗剂ICI 182780所消除,表明ER在DA神经元的分化中起作用。ER在增殖的NSCs和有丝分裂后的DA神经元中均有表达,提示TH阳性神经元的增加是由于DA神经元的诱导和支持。当将细胞移植到小鼠脑中时,17 β-雌二醇还增加了体内源自人NSC的DA神经元的数量。这些结果支持雌激素在神经干细胞移植治疗帕金森病中的可能作用。(C)2004 Wiley-Liss,Inc.
To investigate the effect of estrogen on neuronal differentiation, especially on dopaminergic (DA) neurons, human neural stem cells (NSCs) were differentiated in the presence of 17beta-estradiol. NSCs gave rise to tyrosine hydroxylase (TH)-positive neurons in vitro, the proportion of which was increased by 17beta-estradiol. Increase in TH-positive neurons was abrogated by an estrogen receptor (ER) antagonist, ICI182780, suggesting ERs play a role in differentiation of DA neurons. The observation that ERs were expressed in both proliferating NSCs and postmitotic DA neurons suggested that increase in TH-positive neurons was due to induction and support of DA neurons. 17beta-Estradiol also increased the number of DA neurons derived from human NSCs in vivo when the cells were grafted into mouse brains. These results support a possible role for estrogen in the transplantation of NSCs for Parkinson's disease. (C) 2004 Wiley-Liss, Inc.