MORPHOLOGICAL ANALYSES OF NEURAL AND PARANEURAL GRAFTS

神经和神经旁移植物的形态分析

• 批准号: 3902232
• 负责人: JOHN T HANSEN
• 金额: --
• 依托单位: UNIVERSITY OF ROCHESTER
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3902232
• 关键词: Ceboidea; Parkinson's disease; adrenal medulla; basal ganglia; blood brain barrier; cell differentiation; cell growth regulation; chromaffin cells; disease /disorder model; early embryonic stage; electron microscopy; graft versus host disease; high performance liquid chromatography; histochemistry /cytochemistry; immunochemistry; laboratory rat; nervous system transplantation; neurogenesis; neurons; spinal cord; sympathetic nervous system

The specific aim of this project is to identify, characterize, and determine the potential for use of alternative sources of donor tissue for transplantation in animal models of Parkinson's disease. Because of the ethical, moral, and legal questions surrounding the use of fetal tissues as potential grafts, alternate sources of donor tissue need to be found which will ameliorate the motor deficits caused by Parkinson's disease. This specific aim will be addressed in light of two working hypotheses: (a) Neural crest derivatives belonging to the sympathoadrenal lineage possess inherent phenotypic characteristics which suggest they would be excellent candidates for neural transplantation; and (b) The adult adrenergic derivatives of this lineage, when transplanted into the denervated striatum, will significantly reverse the functional deficits, survive in the host, and continue to elaborate catecholamines. These working hypotheses will be tested both in vitro and in vivo using the three adult adrenergic derivatives of the lineage: (a) principal neurons; (b) adrenal chromaffin cells; and (c) SIF, or glomus cells. The growth and phenotypic differentiation of these cells will be studied using neurochemistry (HPLC), immunohistochemistry, histofluorescence, and scanning and transmission electron microscopy. For my in vivo experiments, the 6-OHDA treated rat model of Parkinson's disease will be used to study the survival and differentiation of implanted cells and tissue fragments of the sympathoadrenal lineage. Moreover, the host response to transplants will be studied ultrastructurally with respect to reactive gliosis, macrophage activity, and the integrity of the blood-brain barrier. In conjunction with these rodent experiments, I will collaborate with those projects using the MPTP primate model of Parkinson's disease by providing EM analysis of their transplants. The behavioral, neurochemical, and morphological results of the rodent studies will be compared with those obtained from the primate experiments. The long-term goals of this work will be to determine the potential of sympathoadrenal cells for use as transplants in humans. The fundamental knowledge gained from these transplantation studies may provide practical clinical approaches to promote recovery from Parkinson's disease and other CNS debilitating diseases such as Alzheimer's disease, Huntington's chorea and CNS trauma.

该项目的具体目标是识别、表征和 确定使用替代捐赠者来源的潜力 帕金森病动物模型中用于移植的组织。 因为围绕着道德、道德和法律问题 利用胎儿组织作为潜在的移植物，替代供体来源 需要找到能改善运动障碍的组织 由帕金森氏症引起。这一具体目标将得到解决 根据两个工作假设：(A)神经峰导数 属于交感-肾上腺血统的人具有固有的 表型特征表明它们将是极好的 神经移植的候选者；和(B)成人肾上腺素能 这一血统的衍生品，当移植到丧失神经的 纹状体，将明显扭转功能缺陷，存活下来 在宿主中，并继续精制儿茶酚胺。这些 工作假说将在体外和体内进行测试，使用 世系的三个成人肾上腺素能衍生物：(A)主要 神经元；(B)肾上腺嗜铬细胞；(C)SIF，或球体细胞。 这些细胞的生长和表型分化将是 研究使用了神经化学(高效液相色谱法)、免疫组织化学、 组织荧光、扫描和透射电子 显微镜。在我的体内实验中，6-OHDA处理的大鼠 帕金森病模型将被用来研究存活和 移植的细胞和组织碎片的分化 交感神经-肾上腺血统。此外，宿主对 将对移植进行超微结构研究，以 反应性胶质细胞增多症、巨噬细胞活性和 血脑屏障。与这些啮齿动物一起 实验，我将与这些项目协作使用 通过提供EM建立帕金森病MPTP灵长类动物模型 对他们的移植进行分析。行为，神经化学，和 啮齿动物的形态研究结果将与 这些都是从灵长类实验中获得的。长期的 这项工作的目标将是确定 交感肾上腺细胞用于人体移植。这个 从这些移植研究中获得的基础知识 可提供实用的临床方法来促进康复 帕金森氏病和其他中枢神经系统衰弱疾病 如阿尔茨海默病、亨廷顿舞蹈病和中枢神经系统损伤。