Core--Neurohistology, Genomic and Bioinformatic Analyses

该核心为NIH PD Udall中心联盟和其他PD科学家提供了独特的数据和方法，用于(1)临床PD细胞治疗原型，以及项目6-7中开发的潜在的未来临床试验参数。(2)新型人多巴胺（DA）中脑细胞标记物用于人类干细胞来源和胎儿DA神经元表征；(3)在项目5的PD啮齿动物功能和神经保护模型中评估人类基因的原位和免疫细胞化学。重要的是，由Core进行的组织学和共聚焦体视学提供了有价值的人类移植数据：包括大小，位置，特定DA神经元的数量，显示A9或A10表型的相对比例，它们的分布，再神经支配人类宿主大脑的能力。在项目6-7中，人类干细胞衍生的多巴胺神经元移植到灵长类动物身上进行了类似的研究。因此，核心的工作提供了

This core provides unique data and methodology to the NIH PD Udall Center Consortium and other PD scientists for (1) PD cell therapy prototypes in the clinic, and for potential future clinical trial parameters developed in Projects 6-7. (2) Novel human dopamine (DA) midbrain cell markers used for human stem cell derived and fetal DA neuronal characterization, and (3) In-situ and immunocytochemistry of human genes evaluated in PD rodent functional and neuroprotection models of Project 5. Critically, histology and confocal stereology performed by the Core, provides valuable human transplant data: including size, location, number of specific DA neurons, relative proportions exhibiting an A9 or A10 phenotype, their distribution, capacity to reinnervate the human host brain. Analogous studies are made of the human stem cell derived dopamine neurons transplanted in primates of Projects 6-7. The Core's work thus provides unique data, functions and expertise, which generate insights for a potential refinement of neuronal transplantation for PD patients. The Core integrates the human transplantation data from 5 external PD clinical groups. These teams have used different cell preparations and surgical techniques and supplies clinical data and postmortem tissue from PD patients whom received human fetal DA cell containing grafts. We have 9 PD post-mortem transplant cases and expect 4-6 additional cases per year. The Biostatistics and Statistical Neuroimaging Lab (Dr Nick Lange, McLean Hospital) analyzes longitudinal relationships of the clinical data and correlate those with postmortem histological data and in vivo data, including PET. The Core also provides a necessary function for Project 5 and the consortium with Duke U. NIH Udall PD Center in the analyses of human tissue for identifying differential gene expression in human SN and VTA and genetic linkage to PD loci (Duke collaboration). The neurodegenerative or protective roles of differentially expressed candidate genes associated with PD by linkage analysis (we currently have 27 genes) at Duke University Udall Center, are further explored and mapped by the Core in PD or age-matched unaffected midbrain human tissue. The core will provide (1) The first comparative neurological examination of different human fetal DA grafts tested in PD for clinical centers worldwide and (2) Markers and analogous analyses of human stem cell derived DA neurons (for Project 6-7). (3) Markers and in-situ analyses of human dopamine neurons related to genes and traits that identify vulnerable ceil populations in PD.