AMINERGIC FUNCTION IN AGING AND ALZHEIMERS DISEASE

此竞争延续应用程序分为五个项目和 三个核心。该计划项目有几个主要的科学目标。自.以来 它一开始，我们就研究了中枢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，以及对基因功能的研究 影响中枢神经生理的条件及其与运动的关系 学习。我们建议将胆碱能变化描述为 衰老中的神经传递也是如此。这包括对 营养因子AS对胆碱能神经元及其靶点的调节 以及对功能和认知之间关系的研究 改装。我们提出了关于长时程增强的研究， 磷酸化及其受兴奋性和抑制性氨基酸的调节 幼年和老年大鼠体内的酸性物质。我们还将研究病毒的分子生物学。 与年龄相关的受体改变。这笔赠款的一个新的重点是研究 钙通道功能及其与神经元变性的关系。一个 第二个新焦点涉及与衰老相关的自由基机制的研究 功能障碍及其自旋陷阱化合物的逆转。脑细胞 移植将被用来区分固有的和 年龄相关变化的外在决定因素。分子生物学和分子生物学 营养因子在神经营养素和转化生长因子β中的功能研究 还提出了家庭问题。这个项目中的实验是 多学科、互动性强。生化和电生理 测量将在动物模型中进行。在最大程度上 可能的，适当的组织，从相同的研究对象 生理学检查将进行生化检查。

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.