Exogenous erythropoietin provides neuroprotection of grafted dopamine neurons in a rodent model of Parkinson's disease
Exogenous erythropoietin provides neuroprotection of grafted dopamine neurons in a rodent model of Parkinson's disease
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DOI：
10.1016/j.brainres.2005.10.078
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发表时间：
2006-01-12
期刊：
影响因子：
2.9
通讯作者：
Sortwell, CE
中科院分区：
文献类型：
--
作者：
Kanaan, NM;Collier, TJ;Sortwell, CE
帕金森病 (PD) 是一种神经退行性疾病，其特征是黑质纹状体系统中多巴胺 (DA) 神经元严重缺失，导致纹状体 DA 耗竭。将胚胎腹侧中脑 (VM) DA 神经元移植到纹状体中是目前探索的一种实验性治疗方法，旨在替代黑质纹状体系统中丢失的 DA，但存在植入神经元存活率较差 (5-20%) 的问题。在这里，我们测试了促红细胞生成素 (Epo) 为胚胎第 14 天 (E14) VM DA 神经元提供神经保护的能力。在体外测试了 Epo 在正常细胞培养条件下增强酪氨酸羟化酶免疫反应性 (TH-ir) 神经元存活的能力。在体外，当在培养物中的 E14 VM 细胞铺板时施用 Epo 并没有增加 TH-ir 神经元的数量。我们还测试了 Epo 在体内增强 E14 VM 移植的功效。用 6-羟基多巴胺单侧损伤的大鼠接受在 Epo 中孵育的移植物。 Epo 治疗使 TH-ir 神经元数量、胞体大小和染色强度显着增加。与对照移植大鼠相比，接受 Epo 处理的移植物的动物表现出显着加速的功能改善和显着更大的旋转不对称的整体改善。这些数据表明，在PD啮齿动物模型中，当Epo与移植细胞一起施用时，胚胎中脑TH-ir神经元的存活率增加。由于体外未观察到 Epo 的直接神经营养作用，因此 Epo 神经保护作用的机制仍有待阐明。 (c) 2005 Elsevier B.V. 保留所有权利。
Parkinson's disease (PD) is a neuro degenerative disease marked by severe loss of dopamine (DA) neurons in the nigrostriatal system, which results in depletion of striatal DA. Transplantation of embryonic ventral mesencephalic (VM) DA neurons into the striatum is a currently explored experimental treatment aimed at replacing lost DA in the nigrostriatal system, but is plagued with poor survival (5-20%) of implanted neurons. Here, we tested the ability of erythropoietin (Epo) to provide neuroprotection for embryonic day 14 (E14) VM DA neurons. Epo was tested in vitro for the ability to augment tyrosine hydroxylase-immunoreactive (TH-ir) neuron survival under normal cell culture conditions. In vitro, Epo did not increase the number of TH-ir neurons when administered at the time of plating the E14 VM cells in culture. We also tested the efficacy of Epo to enhance E14 VM transplants in vivo. Rats unilaterally lesioned with 6-hydroxydopamine received transplants that were incubated in Epo. Treatment with Epo produced significant increases in TH-ir neuron number, soma size, and staining intensity. Animals receiving Epo-treated grafts exhibited significantly accelerated functional improvements and significantly greater overall improvements from rotational asymmetry compared to control grafted rats. These data indicate that the survival of embryonic mesencephalic TH-ir neurons is increased when Epo is administered with grafted cells in a rodent model of PD. As direct neurotrophic effects of Epo were not observed in vitro, the mechanism of Epo neuroprotection remains to be elucidated. (c) 2005 Elsevier B.V. All rights reserved.