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In vivo Studies of Ginkgo biloba Neuroprotection

银杏神经保护的体内研究

基本信息

批准号：
7694239
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
项目类别：
财政年份：
2004
资助国家：
美国
起止时间：
2004-09-15 至 2009-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7694239
关键词：
Affect Aging Alzheimer&apos s Disease Amyloid beta-Protein Animals Apoptotic Attenuated Behavioral Behavioral Assay Biochemistry Biological Assay Brain Caenorhabditis elegans Cell Line Cells Cerebrum 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

项目摘要

DESCRIPTION (provided by applicant): 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) aggregation 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 impairment 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

描述（由申请人提供）：随着我们的平均寿命延长，阿尔茨海默病（AD）的发病率在美国稳步上升。因此，预防或降低这种疾病的发生率是医学研究的高度优先事项。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。大量证据表明EGb 761具有神经保护作用。然而，提取物的作用机制知之甚少。我们之前的研究由美国国立卫生研究院资助，提供了证据，证明EGb 761在体外具有抗淀粉样蛋白β（A β）聚集和抗凋亡特性，这有望成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EGb 761在体内的神经保护机制。我们将继续验证以下假设：EGb 761的神经保护作用是通过抑制A β寡聚化、抗氧化特性和增强生物体的内源性应激反应来实现的。我们将使用转基因C。elegans模型与AD的转基因小鼠模型相结合，以研究A β聚集、氧化和毒性之间的可能联系。本项目的具体目标是：1）通过A β沉积物的荧光染色和A β诱导的转基因C.表达人A β的线虫; 2）通过诱导型转基因C. 3）EGb 761诱导的野生型和转基因C. elegans，采用基因芯片技术; 4）通过检测AD转基因小鼠模型的海马依赖性空间学习能力来确定EGb 761对认知障碍的影响。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神经退行性疾病过程和设计针对神经退行性疾病的治疗策略非常重要

项目成果

期刊论文数量（19）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Anti-depressant natural flavonols modulate BDNF and beta amyloid in neurons and hippocampus of double TgAD mice.

DOI：
10.1016/j.neuropharm.2009.11.002
发表时间：
2010-05
期刊：
NEUROPHARMACOLOGY
影响因子：
4.7
作者：
Hou, Yan;Aboukhatwa, Marwa A.;Lei, De-Liang;Manaye, Kebreten;Khan, Ikhlas;Luo, Yuan
通讯作者：
Luo, Yuan

Fluoxetine protects against amyloid-beta toxicity, in part via daf-16 mediated cell signaling pathway, in Caenorhabditis elegans.

氟西汀可部分通过 daf-16 介导的细胞信号传导途径保护秀丽隐杆线虫免受 β 淀粉样蛋白毒性。