TROPHIC COGRAFT EFFECTS ON MESENCEPHALIC GRAFT VIABILITY

尝试通过移植多巴胺（DA）来增加中枢多巴胺（DA）水平 相关组织提供了可行的治疗策略 帕金森病的治疗方法 临床成功的关键 是开发移植的DA神经元活力和 宿主纹状体的神经再支配显著增加。 生存 移植物中DA能神经元的比率估计为5- 10%，这表明 使用多个捐助者可能是加强 治疗益处。 然而，另一种策略是增加 DA神经元的存活率和生长。 热带和营养因子 来源于纹状体神经元和胶质细胞的细胞参与黑质纹状体通路 形成和维持。 先前的证据表明， 移植物可用于刺激神经突延伸（向性效应）， 移植的多巴胺神经元 我们最近证明了共同移植的纹状体 细胞也表现出对移植的DA神经元的营养作用， 增加DA神经元存活。 由于这些有益的影响， 通过纹状体共同移植的神经元存活和随后的神经突生长 可能发生的机制类似于在其他神经系统中观察到的机制。 靶细胞抑制程序性细胞死亡（凋亡）的系统， 我的建议将尝试1）评估共培养纹状体的 细胞对体外培养中脑DA能神经元凋亡的影响; 确定纹状体共同移植物是否发挥其营养作用， 移植的中脑DA能神经元通过抑制细胞凋亡。 拟议研究的重要性在于能够 结合了检测凋亡细胞的新技术， 应该提供深入了解DA神经元存活的机制， 嫁接 我的长期目标是评估纹状体是否 可以是。

Attempts to increase central dopamine (DA) levels via grafts of pharmacologically relevant tissue provide a viable therapeutic strategy for the treatment of Parkinson's disease. Critical to clinical success is the development of methods whereby grafted DA neuron viability and reinnervation of the host striatum are markedly increased. The survival rate of DA neurons in grafts is estimated to be 5-10%, which suggests that the use of multiple donors may be necessary for enhanced therapeutic benefits. However, an alternate strategy is to increase the survival rate and outgrowth of DA neurons. Tropic and trophic factors derived from striatal neurons and glia aid in nigrostriatal pathway formation and maintenance. Previous evidence suggests that striatal grafts may be used to stimulate neurite extension (tropic effect) of grafted DA neurons. We recently demonstrated that cografted striatal cells also exhibit a trophic effect on grafted DA neurons through increasing DA neuron survival. Since these beneficial effects on DA neuron viability and subsequent neurite outgrowth by striatal cografts may occur by mechanisms similar to those observed in other neural systems in which target cells inhibit programmed cell death (apoptosis), my proposal will attempt to 1) evaluate what effect cocultured striatal cells have on apoptosis in mesencephalic DA neurons in vitro and 2) determine whether striatal cografts exert their trophic effects on grafted mesencephalic DA neurons through the inhibition of apoptosis. The importance of the proposed research lies in the ability to incorporate new technology for the detection of apoptotic cells which should provide insight into mechanisms of DA neuron survival after grafting. My long term objectives are to assess whether striatal cografts can be.