EFFECT OF AGE AND IGF-1 ON NEURONAL STRUCTURE AND FUNCTION

衰老与多种生物学功能的逐渐下降有关， 功能，通常反映局部反应，以系统范围的生理 变化本计划项目的总体目标是调查 与年龄相关的生长激素下降的影响以及由此产生的下降 胰岛素样生长因子-1（IGF-1）在大脑中的作用。IGF-1，像几个 其他生长因子，影响两者的生长和分化 神经元和微血管系统支持巨大的代谢 神经组织内的需求。IGF-1的大量减少发生在 衰老可能导致神经元形式的显著变化， 在大脑中发挥作用。减少的时间相关性 IGF-1水平与认知能力的普遍下降，最近 外源性IGF-1对老年动物给药的观察 提高认知能力，使该因素成为重要的候选人， 进一步研究该项目将测试IGF-1影响 神经元结构和代谢的发育和维持 与年龄相关的IGF-1水平下降显著影响 神经元的结构和活动。这些实验是基于这样一个想法 与衰老相关的认知缺陷至少会导致 部分来自神经元结构的年龄相关变化和/或 调节和维持神经元连接和信号传导的能力。 为了研究IGF-1与神经元形态之间的特定关系， 我们将量化年龄相关变化的程度和复杂性 皮层神经元树突过程的变化，以及 代谢和血管化，在明确定义的区域内， 大脑皮层我们将确定这些变化是否是 IGF-1水平的年龄相关性下降，通过测试他们是否 通过递送给老年动物的外源性IGF-1逆转， 在老龄动物中维持IGF-1水平，并通过比 年轻成年动物中IGF-1的正常下降。最后，我们将研究 IGF-1调节神经元结构的特殊机制， 通过测量IGF-1对发育中的树突的影响来发挥作用， 检查IGF-1与其他神经营养因子的相互作用， 影响神经元的生长和分化，并对影响进行量化 IGF-1信号传导对钙稳态的影响，钙稳态是神经元 发展和功能。这些研究将提供更大的 了解年龄对大脑的影响以及一个人的作用 这是控制这些变化的关键因素。

Aging is associated with progressive declines in a variety of biological functions, often reflecting local responses to system-wide physiological changes. The overall goal of this Program Project is to investigate the effects of the age-related decline in growth hormone and resultant decline in insulin-like growth factor 1 (IGF-1) on the brain. IGF-1, like several other growth factors, influences the growth and differentiation of both neurons and the microvasculature that supports the tremendous metabolic demand within neural tissue. The large decrease in IGF-1 that occurs with senescence is likely to result in significant changes in neuronal form and function within the brain. The temporal correlation of the decrease in IGF-1 levels with a general decline in cognitive abilities, and the recent observation that administration of e exogenous IGF-1 to aged animals increases cognitive abilities, makes the factor an important candidate for further study. This project will test the hypothesis that IGF-1 influences the development and maintenance of neuronal architecture and metabolism such that the age-related decrease in IGF-1 levels significantly affects neurons structure and activity. The experiments are predicated on the idea that the cognitive deficits associated with aging must result, at least in part, from an age-associated change in neuronal architecture and/or a loss in ability to regulate and maintain neuronal connectivity and signaling. To examine the specific relationship between IGF-1 and neuronal form and function we will quantify age-related changes in the extent and complexity of dendritic processes of cortical neurons, as well as changes in metabolism and vascularization, within well-defined regions of the cerebral cortex. We will determine whether those changes are the result of the age-related decrease in IGF-1 levels by testing whether they are reversed by exogenous IGF-1 delivered to aged animals, prevented by maintaining IGF-1 levels in aging animals, and elicited by an earlier than normal decrease in IGF-1 in young adult animals. Finally, we will examine specific mechanisms by which IGF-1 may regulated neuronal structure and function by measuring the effects of IGF-1 on developing dendrites, examining the interaction of IGF-1 with other neurotropic factors that influence neuronal growth and differentiation and quantifying the effects of IGF-1 signaling on calcium homeostasis, a key regulator of the neuronal development and function. These studies will provide a greater understanding of the effects of age on the brain and of the role of one critical factor in regulating those changes.