CORRELATED IMAGING APPROACHES AND MULTISCALE DATABASES FOR RES IN PARKINSONS DI

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。背景与理由：当纹状体多巴胺水平下降50%，黑质内80%的多巴胺能（DA）神经元退化时，PD的临床症状就会出现（Marsden 1990）。路易体形成，PD神经病理学的一个标志性特征，发现在大脑的几个区域，包括黑质。的总和？-核蛋白(?-SYN)在路易体中被发现（Spillantini et al. 1997; Wakabayashi et al. 1997），这表明？- PD中的syn。加州大学圣地亚哥分校的maslihand博士是第一批描述？-SYN同时研究阿尔茨海默病（Iwai et al. 1995; Masliah et al. 1996）。加上最近发现的关键蛋白质(如？-SYN)在PD发病机制中的作用，建立与人类PD相似的转基因小鼠动物模型为研究PD相关神经退行性疾病的预防或逆转策略提供了新的机会。这项工作的提出是及时的，因为我们的小组最近制作并部分描述了PD的动物模型（Rockenstein et al. 2002）。我们与NCMIR的科学家合作，通过对这种PD转基因动物模型进行广泛的成像研究，扩展了我们最初的观察结果。这些研究的结果将被整合到一个神经影像学信息数据库中，以方便对化疗药物在正常和pd样疾病状态下的效果进行定量比较。所选择的成像方法使我们能够覆盖从全脑到超分子复合物的范围，并在其亚细胞位置识别特定蛋白质。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Background & Rationale: The presentation of clinical symptoms of PD occurs when striatal dopamine levels decrease by 50% and 80% of dopaminergic (DA) neurons within the substantia nigra have degenerated (Marsden 1990). Lewy body formations, a hallmark feature of PD neuropathology, are found in several areas of the brain including the substantia nigra. Aggregates of ?-synuclein (?-SYN) are found within Lewy Bodies (Spillantini et al. 1997; Wakabayashi et al. 1997), which suggests a role for ?-SYN in PD. Dr. Masliahand colleages at UC San Diego was among the first to characterize ?-SYN while working on Alzheimer¿s disease (Iwai et al. 1995; Masliah et al. 1996). Together with recent discoveries of involvement of key proteins (like ?-SYN) in the pathogenesis of PD, the development of transgenic mouse animal models that closely resemble human PD are providing new opportunities to study strategies to prevent or reverse the neurodegeneration associated with PD. The proposed work is timely as our group has recently produced, and partially characterized an animal model of PD (Rockenstein et al. 2002). In collaboration with NCMIR scientists, we are extending our original observations by conducting extensive imaging studies on this transgenic animal model of PD. The results of these studies will be integrated into a database of neuroimaging information to facilitate quantitative comparisons of the effects of chemotherapeutic agents in normal and PD-like disease states. The selected imaging methods allow us to cover the scales from whole brain to supramolecular complexes, with specific proteins identified in their subcellular locations.