TROPHIC COGRAFT EFFECTS ON MESENCEPHALIC GRAFT VIABILITY

营养性移植物对中脑移植物活力的影响

• 批准号: 2036619
• 负责人: Caryl E Sortwell
• 金额: $ 2.96万
• 依托单位: ROSALIND FRANKLIN UNIV OF MEDICINE & SCI
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/2036619
• 关键词: Parkinson's disease; Rodentias; apoptosis; cell cell interaction; corpus striatum; disease /disorder model; immunocytochemistry; mesencephalon; mixed tissue /cell culture; nervous system transplantation

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.

尝试通过移植增加中枢多巴胺（DA）水平 药理学相关组织提供可行的治疗策略 用于治疗帕金森病。 对临床成功至关重要 是通过移植 DA 神经元活力和 宿主纹状体的神经支配明显增加。 生存 移植物中 DA 神经元的比例估计为 5-10%，这表明 可能需要使用多个捐助者来加强 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。 热带和营养因素 源自纹状体神经元和神经胶质细胞，有助于黑质纹状体通路 形成和维护。 先前的证据表明纹状体 移植物可用于刺激神经突延伸（热带效应） 移植的 DA 神经元。 我们最近证明，共同移植的纹状体 细胞还通过以下方式对移植的 DA 神经元表现出营养作用 增加 DA 神经元的存活率。 由于这些对 DA 的有益影响 纹状体移植物的神经元活力和随后的神经突生长 可能通过类似于在其他神经中观察到的机制发生 靶细胞抑制程序性细胞死亡（细胞凋亡）的系统， 我的建议将尝试1）评估共培养纹状体的效果 细胞对体外中脑 DA 神经元的凋亡有影响，2) 确定纹状体移植物是否发挥其营养作用 通过抑制细胞凋亡来抑制移植的中脑DA神经元。 拟议研究的重要性在于能够 结合检测凋亡细胞的新技术 应该可以深入了解 DA 神经元存活后的机制 嫁接。 我的长期目标是评估纹状体是否 共移植物可以。