AMINERGIC FUNCTION IN AGING AND ALZHEIMERS DISEASE

这一竞争性延续申请分为五个项目， 三个核心 该计划项目有几个主要的科学目标。 以来 其成立之初，我们已经研究了中央去甲肾上腺素能的变化， 衰老过程中的神经传递 这包括对 分子和细胞生物学水平，以及功能的研究， 对中枢神经元生理学的影响及其与运动的相关性 学习 我们建议描述胆碱能的变化， 神经传递在衰老中的作用 这包括对 通过营养因子调节胆碱能神经元及其靶点，如 以及对功能和认知之间关系的研究 改变。 我们已经提出了对长时程增强的研究， 磷酸化，以及它们通过兴奋性和抑制性氨基酸的调节 酸在年轻和老年大鼠。 我们还将研究 年龄相关的受体变化。 该补助金的一个新重点是研究 钙通道功能及其与神经元变性的关系。 一 第二个新的重点是研究与年龄有关的自由基机制， 功能障碍及其通过自旋陷阱化合物的逆转。 脑细胞 移植将被用来区分内在的和 年龄相关变化的外在决定因素。 分子生物学和 神经营养因子和转化生长因子β中营养因子的功能研究 家庭也提出了。 本程序中的实验包括 多学科和互动。 生化和电生理 将在动物模型中进行测量。 最大程度 来自研究的相同受试者的可能的适当组织 生理学将被生化检查。

This competing continuation application is divided into five projects and three cores. The program project has several major scientific aims. Since its inception, we have studied changes in central noradrenergic neurotransmission during aging. This includes studies of mechanisms at the molecular and cell biological levels, as well as studies of function in terms of effects on central neuronal physiology and correlation with motor learning. We propose to characterize changes in cholinergic neurotransmission in aging as well. This includes studies of the regulation of cholinergic neurons and their targets by trophic factors, as well as studies of the relationship between functional and cognitive alterations. We have proposed studies on long term potentiation, phosphorylation, and their regulation by excitatory and inhibitory amino acids in young and aged rats. We will also study the molecular biology of age-related receptor changes. A new focus of this grant is the study of calcium channel function and its relationship to neuronal degeneration. A second new focus involves study of free radical mechanisms in aged-related dysfunctions and their reversal by spin-trap compounds. Brain cell transplants will be utilized to differentiate between intrinsic and extrinsic determinants of age-related changes. Molecular biological and functional studies of trophic factors in the neurotrophin and TGF beta families are also proposed. The experiments in this program are multidisciplinary and interactive. Biochemical and electrophysiological measurements will be made in animal models. To the greatest extent possible, appropriate tissues from the same subjects studied physiologically will be examined biochemically.