NEURAL AND PARANEURAL GRAFTS IN PARKINSONIANS MODELS

帕金森氏病是一种持续进行的神经退行性疾病， 超过50万美国人患有这种疾病 帕金森症患者可以 由于左旋多巴和其他药物治疗， 但大多数人在后期的生活质量会稳步下降 疾病。 该项目旨在（i）系统地 研究性肾上腺嗜铬细胞移植作为治疗 治疗帕金森病，（ii）更好地了解机制 啮齿动物和非人类帕金森综合征的潜在功能恢复 帕金森病的灵长类动物模型。 目前的项目包括三个项目和两个核心设施。 在 项目1，加什博士将严格测试的假设，增加 纹状体内移植物中嗜铬细胞存活率显著增加 帕金森病灵长类动物的行为恢复。 在项目2中，诺特博士 将深入研究灵长类许旺细胞的特性， 嗜铬细胞的生物测定，免疫母细胞和原位杂交， mRNA。 她还将评估灵长类嗜铬细胞对 它们将在植入部位暴露的因素包括aFGF， 细胞因子、巨噬细胞衍生因子和左旋多巴。 汉森博士，在项目 3、采用选择性损伤大鼠模型将检验宿主的假设， 发芽反应对于恢复纹状体多巴胺水平很重要， 可能是改善功能缺陷的唯一最重要的事件 这是由于纹状体中的多巴胺耗尽造成的。 总的来说，这些研究不仅应该增加我们对 这些过程对帕金森症的功能恢复很重要， 在设计新的治疗方法方面也有显著的益处， 帕金森病的治疗方法

Parkinson's disease is a relentlessly progressive neurodegenerative disorder afflicting over 500,000 Americans. Patients with parkinsonism can expect to live a normal lifespan due to levodopa and other drug therapies, but most experience a steadily eroding quality of life in the later stages of the disease. This program project was organized to (i) systematically investigative adrenal chromaffin cell transplantation as an approach to treating Parkinson's disease, and (ii) better understand the mechanisms underlying functional recovery from parkinsonism in rodent and nonhuman primate models of Parkinson's disease. The present program consists of three projects and two core facilities. In Project 1, Dr. Gash will critically test the hypothesis that increasing chromaffin cell survival in intrastriatal grafts significantly increases behavioral recovery in parkinsonian primates. In Project 2, Dr. Notter will characterize in depth the properties of primate Schwann cells and chromaffin cells by bioassays, immunoblasts and in situ hybridization for mRNA. She will also evaluate the response of primate chromaffin cells to factors they will be exposed to in implant sites including a aFGF, cytokines, macrophage-derived factors and levodopa. Dr. Hansen, in Project 3, using a selective lesion rat model will test the hypothesis that a host sprouting response is important for restoring striatal dopamine levels and may be the single most important event in ameliorating functional deficits that result from dopamine depletion in the striatum. Collectively, these studies should not only increase our understanding of the processes important for functional recovery from parkinsonism but should also be of significant benefit in designing new therapeutic approaches to the treatment of Parkinson's disease.