Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model
Combined treatment of neurotrophin-3 gene and neural stem cells is ameliorative to behavior recovery of Parkinson's disease rat model
复制标题
神经营养素3基因与神经干细胞联合治疗可改善帕金森病大鼠模型的行为恢复
DOI：
10.1016/j.brainres.2008.12.016
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发表时间：
2009-02-27
期刊：
影响因子：
2.9
通讯作者：
Wen, Tieqiao
中科院分区：
文献类型：
--
作者：
Gu, Shuting;Huang, Hai;Wen, Tieqiao
神经干细胞移植疗法被开发用于替换丢失或受损的神经细胞治疗神经退行性疾病，包括帕金森病（PD），其中多巴胺能神经元细胞丢失。生长因子神经营养因子-3（NT-3）已被证明在大脑发育过程中促进神经再生、分化和迁移。在本报告中，我们构建了内源性表达神经营养因子-3 （rNSC-NT3）的大鼠神经干细胞，并将其移植到6-羟多巴胺（6-OHDA）治疗的帕金森大鼠体内。采用实时荧光定量PCR、Western blot和免疫细胞化学等分子方法鉴定NT-3的表达和种植细胞的分化情况。行为恢复也进行了测试。结果表明，神经营养因子-3基因和神经干细胞联合治疗对逆转帕金森病的主要症状具有功能上的影响，显著减少阿吗啡引起的旋转不对称，提高空间学习能力。rNSCs-NT3能够分化为腹侧被叶区（VTA）和内侧前脑束（MFB）的dompaminergic神经元，并在病变部位周围迁移。内源性表达的NT-3对神经干细胞具有诱导和营养作用。在多巴赤字大鼠模型中，rNSCs- nt3在再生酪氨酸羟化酶阳性细胞数量和迁移距离方面表现出比rNSCs更高的活性，行为改善。这些发现表明，内源性表达NT-3的神经干细胞将是治疗帕金森病的更好的移植物候选。(C) 2008 Elsevier B.V.版权所有
Neural stem cell transplantation therapy was developed for replacing lost or damaged neural cells for the neurodegenerative disease, including Parkinson's disease (PD), in which dopaminergic neuron cells are lost. The growth factor, neurotrophin-3(NT-3), has been shown to promote neuroregeneration, differentiation and migration during brain development. In this report, we construct rat neural stem cells that express neurotrophin-3 endogenously (rNSC-NT3) and transplant them into 6-hydroxydopa mine (6-OHDA)-treated Parkinsonian rats. Molecular approaches including quantitative real time PCR, Western blot and immunocytochemistry were used to identify the expression of NT-3 and the differentiation of planted cells. Behavioral recover was also tested. The result indicated that combined treatment of neurotrophin-3 gene and neural stem cells had a functional impact on reversing the main symptoms of the Parkinson's disease that significantly reduced apomorphine-induced rotational asymmetry and improved spatial learning ability. The rNSCs-NT3 is able to differentiate into dompaminergic neuron in the ventral tegmental area (VTA) and the medial forebrain bundle (MFB), and migrated around the lesion site. Endogenous expressed NT-3 exerts induction and trophic effects on neural stem cells. The rNSCs-NT3 showed higher activity than the rNSCs in regenerating tyrosine hydroxylase positive cell numbers and migrating distance, behavior improving in this dopa-deficit rat model. These findings suggest that the neural stem cells expressed NT-3 endogenously would be a better graft candidate for the treatment of Parkinson's disease. (C) 2008 Elsevier B.V. All rights reserved.