NEUROTROPHIC SUPPORT IN AGING AND ALZHEIMER'S DISEASE

年龄相关的认知能力丧失，最严重的经历是 阿尔茨海默病，影响着越来越多的老年人。 大脑皮层、海马神经元的变性和死亡 基底前脑是导致这种认知丧失的主要事件。 超能力。如果减轻这种退行性事件的治疗方法是 发展起来，理解分子和 参与维持的细胞机制，神经元 中枢神经系统的可塑性和再生。增长因素 它们的受体代表了一种主要的分子机制 促进神经元存活和再生。这个项目将 探讨成纤维细胞生长因子在衰老和衰老中的作用 退化的中枢神经系统。该项目的重点将是酸性成纤维细胞生长因子(AFGF)， 碱性成纤维细胞生长因子、成纤维细胞生长因子-5及其受体。这些因素具有特殊性。 兴趣在于它们可以促进神经元存活和有丝分裂 非神经细胞对损伤的反应；此外，它们存在于 大脑皮层、海马区和 基底前脑。本研究的目标是确定 FGFs的功能在衰老和阿尔茨海默病中受到影响。这个 研究的具体目的是：1.确定细胞水平和细胞 正常成人特异性成纤维细胞生长因子及其受体的分布 海马体、大脑皮层和基底前脑。2.确定更改 正常人体内特异性FGFs和FGFRs的水平及细胞分布 在与年龄相关的海马区功能障碍的动物模型中，以及在 阿尔茨海默氏症。3.描述可能导致衰老的机制 FGFs和FGFRs表达的相关变化。4.要刻画 成纤维细胞生长因子在海马区、大脑皮层和前脑的生理作用。5.测试 外源性应用FGFs能否改善上述缺陷 在与年龄相关的海马区功能障碍的动物模型中观察到。这个 这项研究将使用生化、免疫化学和分子的组合 确定表达水平、分布和变化的技术 成纤维细胞生长因子及其受体的表达。这项研究将集中于调查这一角色 这些分子在阿尔茨海默病和老年动物模型中的作用 相关的认知功能障碍。

Age related loss of cognitive ability, most severely experienced in Alzheimer's disease, affects an increasing number of the elderly. Degeneration and death of neurons in the cerebral cortex, hippocampus and basal forebrain are the main events causing such loss of cognitive abilities. If therapies to attenuate such degenerative events are to be developed, it is of central importance to understand the molecular and cellular mechanisms that are involved in the maintenance, neuronal plasticity and regeneration of the central nervous system. Growth factors and their receptors represent one of the main molecular mechanisms promoting neuronal survival and regeneration. This project will investigate the role of fibroblast growth factors (FGF) in the aging and degenerating CNS. The focus of the project will be on acidic FGF (aFGF), basic FGF (bFGF), FGF-5 and their receptors. These factors are of specific interests in that they can promote neuronal survival as well as mitogenic responses of non-neuronal cells to injury; in addition they are present in specific cellular populations within cerebral cortex, hippocampus and basal forebrain. It is the goal of the present study to determine how the function of the FGFs is affected in aging and Alzheimer's disease. The specific aims of the study are: 1.To determine the levels and cellular distributions of specific FGFs and FGF receptors in normal adult hippocampus, cerebral cortex and basal forebrain. 2.To determine changes in levels and cellular distribution of specific FGFs and FGFRs in normal aging, in an animal model of age related hippocampal dysfunction, and in Alzheimer's disease. 3.To characterize mechanisms that may cause age related changes in the expression of FGFs and FGFRs. 4.To characterize the physiological role of FGFs in hippocampus, cortex and forebrain. 5.To test whether exogenous application of FGFs can ameliorate the deficiencies observed in an animal model of age related hippocampal dysfunction. The study will use a combination of biochemical, immunochemical, and molecular techniques to determine the levels, distribution and changes in expression of FGFs and FGF receptors. The study will focus on investigating the role of these molecules in Alzheimer's disease and in an animal model of-age related cognitive dysfunction.