In vivo Studies of Ginkgo biloba Neuroprotection

银杏神经保护的体内研究

• 批准号: 7455616
• 负责人: YUAN LUO
• 金额: $ 4.5万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-15 至 2008-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7455616
• 关键词: Affect; Aging; Alzheimer' s Disease; Amyloid beta-Protein; Animals; Apoptotic; Attenuated; Behavioral; Behavioral Assay; Biochemistry; Biological Assay; Brain; Caenorhabditis elegans; Cell Line; Cells; Cerebrum; Cognitive; Collaborations; DNA Microarray Chip; DNA Microarray format; Data; Dementia; Deposition; Disease; EGb761; Exhibits; Fluorescence; Functional disorder; Funding; Genes; Genetic Transcription; Ginkgo biloba; Ginkgo biloba extract; Goals; Herbal Medicine; Hippocampus (Brain); Human; Imagery; Impaired cognition; In Vitro; Incidence; Individual; Investigation; Kinetics; Learning; Left; Link; Longevity; Measures; Medical Research; Memory; Metabolism; Methods; Microarray Analysis; Modeling; Molecular Biology; Nematoda; Nerve Degeneration; Neurodegenerative Disorders; Neurons; Neuroprotective Agents; Organism; Paralysed; Process; Property; Protein Analysis; Proteins; Publications; RNA Interference; Rate; Reactive Oxygen Species; Research; Staining method; Stains; Stress; Temperature; Testing; Therapeutic; Tissues; Toxic effect; Transcriptional Activation; Transgenic Mice; Transgenic Model; Transgenic Organisms; United States; United States National Institutes of Health; Up-Regulation; Western Blotting; Wild Type Mouse; base; biological adaptation to stress; comparative; design; feeding; gel electrophoresis; in vivo; in vivo Model; morris water maze; mouse model; neuroprotection; oxidation; prevent; repaired

The incidence of Alzheimer's disease (AD) has steadily increased in the United States as our average lifespan has lengthened. Thus, the means to prevent or reduce the rate of this disorder is a high priority for medical research. A standardized extract of Ginkgo biloba leaves (EGb 761) has been used for treatment of certain cerebral dysfunctions and dementias associated with aging and AD. Substantial evidence indicates that EGb 761 has neuroprotective effects. The action mechanisms of the extract are, however, poorly understood. Our previous studies funded by the National Institutes of Health provided evidence for the anti-amyloid beta (A beta) aggergation and anti-apoptotic properties of EGb 761 in vitro, which hold promise as potentially important neuroprotective mechanisms of action. The goal of this interdisciplinary project is to further our understanding of the neuroprotective mechanisms of EGb 761 in vivo. We will continue to test the hypothesis that the neuroprotective effect of EGb 761 is achieved by inhibition of A beta oligomerization, antioxidative properties and augmentation of an organism's endogenous stress-response. We will use transgenic C. elegans models in conjunction with a transgenic mouse model of AD to study possible links between A beta aggregation, oxidation and toxicity. The specific aims of the present project are: 1) to correlate effects of EGb 761 on A beta aggregation and toxicity through fluorescence staining of A beta deposits and behavioral analysis of A beta-induced paralysis in the transgenic C. elegans expressing human A beta; 2) to define activities of single constituents of EGb 761 against A beta-induced oxidation through kinetic study of protein carbonyls in an inducible transgenic C. elegans; 3) to implicate changes in gene transcription profile induced by EGb 761 in the wild type and the transgenic C. elegans, using DNA microarray method, 4) to determine effects of EGb 761 on cognitive _mpairment through testing hippocampus-dependent spatial learning in a transgenic mouse model of AD. Previous results and preliminary data show the feasibility of this project. A better understanding of the 'mechanisms of EGb 761 neuroprotection will be important for understanding of the underlying neurodegenerative processes and for designing therapeutic strategies that target neurodegenerative disorders.

在美国，阿尔茨海默病（AD）的发病率稳步上升， 寿命延长了。因此，预防或降低这种疾病的发生率的方法是一个高度优先事项， 医学研究银杏叶的标准化提取物（EGb 761）已被用于治疗 某些与衰老和AD相关的脑功能障碍和痴呆。实质证据显示 EGb 761具有神经保护作用。但其作用机制尚不清楚 明白我们先前由美国国立卫生研究院资助的研究为以下结论提供了证据： EGb 761在体外具有抗淀粉样蛋白β（A β）聚集和抗凋亡特性， 作为潜在的重要神经保护作用机制。 这个跨学科项目的目标是进一步了解神经保护作用， EGb 761的体内机制。我们将继续测试的假设，即神经保护作用的 EGb 761通过抑制A β寡聚化、抗氧化特性和增强 生物体的内源性应激反应。我们将使用转基因C。elegans模型与 AD转基因小鼠模型，研究A β聚集、氧化和毒性之间可能的联系。 本项目的具体目标是：1）将EGb 761对A β聚集的影响与 通过A β沉积物的荧光染色和A β诱导的麻痹的行为分析的毒性 在转基因C.表达人A β的线虫; 2）确定EGb的单个组分的活性 761对A β诱导的氧化的抑制作用。 3）暗示EGb 761在野生型和线虫中诱导的基因转录谱的变化， 转基因长采用基因芯片技术检测EGb 761对小鼠认知功能的影响。 通过在AD转基因小鼠模型中测试大脑皮层依赖的空间学习来研究AD的损害。 前期研究结果和初步数据表明了该项目的可行性。更好地理解 EGb 761的神经保护机制对于理解潜在的 用于设计靶向神经退行性疾病的治疗策略， 紊乱