CALCIUM REGULATION IN BRAIN AGING AND ALZHEIMERS DISEASE

这是一份继续竞争项目的申请 该项目的重点是钙调节在大脑衰老中的作用 和阿尔茨海默病以及神经元的基本过程 易损性.在前一时期，该计划的调查人员 项目能够阐明钙的一些关键变化， 在衰老动物的脑细胞中的调节和在 神经变性/阿尔茨海默病。还获得了新的证据 钙调节的这种变化可能与 神经退化过程此外，计划项目调查员 发现了新的线索，并对几个假设进行了测试， 年龄相关钙调节异常的可能原因。 在下一个时期，建议开展全面的 脑老化中钙调节的研究进展 阿尔茨海默氏症，使用先进的钙成像技术， 电生理学和分子生物学。PGP项目（PGP） 由五个项目和一个行政核心组成。这些项目将 测试几个假设的初始原因钙失调 包括类固醇激素的作用（其具有特定的靶位点 在脑细胞中），改变功能的基因表达，以及脑能量 新陈代谢.钙调节异常的特定神经元位点， 包括膜离子通道，内质网， 线粒体、细胞骨架和细胞内信号通路。在 此外，相关研究将直接在尸检脑中进行 来自AD和对照受试者的组织。 PGP汇集了自然感兴趣的调查人员， 钙调节和神经毒性的机制， 先进的技术。这些调查人员将共享重叠的模型 并在相关主题上进行广泛合作，从而确保强大的 跨学科和多学科的方法， 正在调查的问题。

This is an application for a competitive continuation of a program project that focuses on the role of Calcium Regulation in Brain Aging and Alzheimer's Disease and on basic processes that underlie neuronal vulnerability. During the prior period, investigators in the program project were able to elucidate a number of key changes in calcium regulation in brain cells of aging animals and in models of neurodegeneration/Alzheimer's disease. New evidence was also obtained that such changes in calcium regulation may be directly relevant to neurodegenerative processes. In addition, program project investigators uncovered new leads and performed tests of several hypotheses on the possible causal bases of age-related calcium dysregulation. During the next period, it is proposed to pursue a comprehensive approach to the study of calcium regulation in brain aging and Alzheimer's disease, using advanced technologies for calcium imaging, electrophysiology and molecular biology. The Program Project (PGP) will consist of five projects and one administrative core. The projects will test several hypotheses of the initial causes of calcium dysregulation including the role of steroid hormones (which have specific target sites in brain cells), altered gene expression of function, and brain energy metabolism. Specific neuronal sites of calcium dysregulation that will be examined include membrane ion channels, endoplasmic reticulum, mitochondria, the cytoskeleton and intracellular signaling pathways. In addition, related studies will be conducted directly on autopsy brain tissues from AD and control subjects. The PGP brings together investigators with a natural interest in the mechanisms of calcium regulation and neurotoxicity, and skills in advanced technologies. These investigators will share overlapping models and collaborate extensively on related subjects, thereby ensuring strong cross-fertilization and multi-disciplinary approaches to the key questions under investigation.