Confocal Microscope for the Study of Neurologic Diseases

描述（由申请人提供）：本申请申请资金用于购买一台新的蔡司共聚焦显微镜，用于神经系统疾病的分子机制研究，特别是阿尔茨海默病（AD），帕金森病（PD）和多发性硬化症（MS）。遗传和环境因素都有助于这些慢性，未解决的中枢神经系统疾病的发病机制。神经系统疾病中心的几个实验室的主要目标是检查确定在这些疾病中起致病作用的基因产物，以确定其内源性功能及其突变或积累的病理后果。通过了解这些过程，可以确定新的治疗干预靶点。对于阿尔茨海默病，APP和早老素基因的突变已经被确定，这些突变会导致疾病的早期发作和侵袭性形式。使用共聚焦显微镜，这些基因表达改变的功能后果可以有效地在体内啮齿动物模型和体外细胞模型中分析。同样，α -突触核蛋白、PINK1、LRRK2和Parkin等基因的突变与PD有关，共聚焦显微镜的使用也极大地促进了它们在疾病模型中的研究。多发性硬化症是一种中枢神经系统退行性脱髓鞘疾病。在我们科，小胶质瘤和神经干细胞活化在多发性硬化症的病理和可能的治疗中的作用在许多研究中得到了解决。共聚焦显微镜是研究实验啮齿动物模型和基于细胞的疾病模型中这些过程的绝对必要技术。

DESCRIPTION (provided by applicant): This application requests funds to purchase a new Zeiss confocal microscope to be used on a daily basis in the study of the molecular mechanisms underlying neurologic disease, specifically Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Both genetic and environmental factors contribute to the pathogenesis of each of these chronic, unsolved CNS diseases. A primary goal of several labs in the Center for Neurologic Diseases is to examine the gene products identified to play a pathogenic role in these diseases, in order to determine both their endogenous functions and the pathological consequences of their mutation or accumulation. Through the understanding of these processes, novel targets for therapeutic intervention can be identified. For AD, mutations have been identified in the genes APP and Presenilin that result in an early onset, aggressive form of the disease. Using confocal microscopy, the functional consequences of alteration of expression of these genes can be effectively analyzed in vivo in rodent models as well as in vitro in cellular models. Similarly, mutations in genes such as alpha-synuclein, PINK1, LRRK2, and Parkin are linked to PD and their study in our disease models also benefits greatly from the use of the confocal microscope. MS is a degenerative demyelinating disease of the central nervous system. In our department, the roles of microgliosis and neural stem cell activation in the pathology and possible treatment of MS are addressed in numerous studies. Confocal microscopy is an absolutely essential technique for the study of these processes in experimental rodent models and cell based models of the disease. PUBLIC HEALTH RELEVANCE: The several laboratories in our department (the Center for Neurologic Diseases) study the causes and possible treatments of neurological diseases such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. This application requests funds to cover the cost of a new Zeiss confocal microscope, as the use of confocal microscopy is critical for the study of how alteration of genes and the environment affect the function of neurons and glia in models of these diseases.