CORRELATED IMAGING APPROACHES AND MULTISCALE DATABASES FOR RES IN PARKINSONS DI

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。背景与原理：帕金森病的临床症状表现为纹状体多巴胺水平下降50%和80%黑质中的多巴胺能神经元变性(Marsden 1990)。路易体形成是帕金森病神经病理学的一个显著特征，在大脑的几个区域，包括黑质，都有发现。在路易小体中发现了？-突触核蛋白聚集体(？-SYN)(Spillantini等人)。1997年；Wakabayashi等人。1997)，这表明了？-SYN在PD中的作用。加州大学圣地亚哥分校的马斯利亚汉德博士是第一批在治疗阿尔茨海默病时表征？-SYN的同事之一(岩井等人)。1995年；Masliah等人。1996年)。随着最近发现的关键蛋白(如？-SYN)参与帕金森病发病机制的发现，与人类帕金森病非常相似的转基因小鼠动物模型的发展为研究预防或逆转与帕金森病相关的神经变性的策略提供了新的机会。这项拟议的工作是及时的，因为我们的小组最近制作了一种PD的动物模型(Rockenstein等人)，并部分描述了该模型的特征。2002年)。在与NCMIR科学家的合作下，我们正在通过对这种PD转基因动物模型进行广泛的成像研究来扩展我们最初的观察结果。这些研究的结果将被整合到神经成像信息数据库中，以便于定量比较化疗药物在正常和类PD疾病状态下的效果。选定的成像方法使我们能够覆盖从整个大脑到超分子复合体的范围，并在其亚细胞位置识别特定的蛋白质。

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.