NEUROTROPHIC SUPPORT IN AGING AND ALZHEIMER'S DISEASE

与年龄相关的认知能力丧失，最严重的发生在 老年痴呆症影响着越来越多的老年人。 大脑皮层、海马和海马神经元的变性和死亡 基底前脑是导致这种认知功能丧失的主要事件 能力.如果要减轻这种退行性事件的治疗， 发展，这是至关重要的是要了解分子和 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。生长因子 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。该项目将 研究成纤维细胞生长因子（FGF）在衰老和 中枢神经系统退化该项目的重点将是酸性成纤维细胞生长因子， 碱性成纤维细胞生长因子（bFGF）、成纤维细胞生长因子-5（FGF-5）及其受体。这些因素是特定的 它们可以促进神经元存活以及促有丝分裂， 非神经元细胞对损伤的反应;此外，它们存在于 大脑皮层、海马和海马内的特定细胞群， 基底前脑本研究的目的是确定 FGF的功能在衰老和阿尔茨海默病中受到影响。的 本研究的具体目的是：1.确定水平和细胞 FGF及其受体在正常成人中的分布 海马、大脑皮层和基底前脑。2.确定变更 正常人中特异性FGF和FGFR的水平和细胞分布 在与年龄相关的海马功能障碍的动物模型中，以及在 老年痴呆症3.描述可能导致衰老的机制 FGF和FGFR表达的相关变化。4.表征 FGF在海马、皮质和前脑中的生理作用。5.测试 外源性应用FGFs是否可以改善这些缺陷 在年龄相关的海马功能障碍的动物模型中观察到。的 这项研究将结合生物化学、免疫化学和分子生物学方法， 确定表达水平、分布和变化的技术 FGF和FGF受体。这项研究将侧重于调查 这些分子在阿尔茨海默氏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.