Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats
Involvement of GDNF in neuronal protection against 6-OHDA-induced parkinsonism following intracerebral transplantation of fetal kidney tissues in adult rats
复制标题
DOI：
10.1006/nbdi.2001.0410
复制
发表时间：
2001-08-01
影响因子：
6.1
通讯作者：
Wang, Y
中科院分区：
文献类型：
--
作者：
Borlongan, CV;Zhou, FC;Wang, Y
外源性应用转化生长因子-β（TGF β）家族蛋白，包括胶质细胞系源性神经营养因子（GDNF）、神经营养素、激活素和骨形态发生蛋白，已被证明可以保护许多神经系统疾病模型中的神经元。找到含有多种这些蛋白质的组织来源可能会促进治疗神经退行性疾病的最佳有益效果。由于胎儿肾脏表达许多TGF β营养因子，我们将这些组织直接移植到单侧6-羟基多巴胺损伤后的黑质中。我们发现，接受胎肾组织移植的动物表现出（1）明显减少的偏侧帕金森病不对称行为，（2）在受损的黑质和纹状体中接近正常的酪氨酸羟化酶免疫反应性，（3）在受损的纹状体中保留K+诱导的多巴胺释放，（4）移植物中高水平的GDNF蛋白。相比之下，接受成年肾组织移植的损伤动物表现出显着的行为缺陷，多巴胺能耗竭，K+介导的纹状体多巴胺释放减少，移植物内GDNF蛋白水平低。目前的研究表明，胎儿肾组织移植可以保护黑质纹状体多巴胺能系统对神经毒素诱导的帕金森综合征，可能通过协同释放GDNF和其他几种神经营养因子。(C)北京：科学出版社.
Exogenous application of transforming growth factors-beta (TGF beta) family proteins, including glial cell line-derived neurotrophic factor (GDNF), neurturin, activin, and bone morphogenetic proteins, has been shown to protect neurons in many models of neurological disorders. Finding a tissue source containing a variety of these proteins may promote optimal beneficial effects for treatment of neurodegenerative diseases. Because fetal kidneys express many TGF beta trophic factors, we transplanted these tissues directly into the substantial nigra after a unilateral 6-hydroxydopamine lesion. We found that animals that received fetal kidney tissue grafts exhibited (1) significantly reduced hemiparkinsonian asymmetrical behaviors, (2) a near normal tyrosine hydroxylase immunoreactivity in the lesioned nigra and striatum, (3) a preservation of K+-induced dopamine release in the lesioned striatum, and (4) high levels of GDNF protein within the grafts. In contrast, lesioned animals that received grafts of adult kidney tissues displayed significant behavioral deficits, dopaminergic depletion, reduced K+-mediated striatal dopamine release, and low levels of GDNF protein within the grafts. The present study suggests that fetal kidney tissue grafts can protect the nigrostriatal dopaminergic system against a neurotoxin-induced parkinsonism, possibly through the synergistic release of GDNF and several other neurotrophic factors. (C) 2001 Academic Press.