Seahorse XF-96 Analyzer for Non-Invasive Monitoring of Mitochondrial Function

Seahorse XF-96 分析仪用于无创监测线粒体功能

• 批准号: 7792840
• 负责人: Ahmet Hoke
• 金额: $ 17.18万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-15 至 2011-08-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7792840
• 关键词: Affect; Axon; Biological Assay; Cell Line; Cells; Dementia; Energy Metabolism; Genus Hippocampus; HIV; Life; Measures; Mitochondria; Motor Neuron Disease; Multiple Sclerosis; Neurodegenerative Disorders; Neuroglia; Neurologist; Neurons; Oxidative Stress; Oxygen Consumption; Pathogenesis; Peripheral Nervous System Diseases; Play; Population; Preclinical Drug Evaluation; Principal Investigator; Production; Protons; Research; Research Personnel; Role; Sampling; Signal Transduction; Slice; Synapses; Testing; Time; axonal degeneration; disease mechanisms study; extracellular; in vitro Model; instrument; mitochondrial dysfunction; nervous system disorder; neuron loss; non-invasive monitor; public health relevance; research study

DESCRIPTION (provided by applicant): Mitochondria play a critical role in pathogenesis of many neurological disorders, partly because of the unique function of mitochondria in neuronal activity at the synapses and along the axons. In vitro models of neurodegenerative disorders utilizing primary neuronal cultures, explants/slice cultures and neuronal and glial cell lines have been developed to study disease mechanisms and establish assays for drug screening. Role of mitochondria in oxidative stress, axonal degeneration, cell death and neuronal energy metabolism are being studied in these in vitro models, but most of the currently available assays have limitations. Many of the assays on mitochondrial function require isolation of mitochondria from the cells eliminating contribution of intracellular signaling on mitochondrial function. Other assays are indirect and look at consequences of mitochondrial dysfunction and are often static assays. An instrument that evaluates mitochondrial function in real-time within neuronal and glial cells would be of great value to test hypotheses on the relevance of mitochondria in neurodegenerative disease pathogenesis. The Seahorse XF-96 analyzer is such an instrument allowing one to evaluate oxygen consumption rate (OCR) and extracellular acidification rate (ECAR, i.e. proton production) in living cells in real-time. The principal investigator and major users of the proposed XF-96 are all neurologists and neuroscientists studying neurodegenerative disease mechanisms, including motor neuron disease, multiple sclerosis, human immunodeficiency virus (HIV) dementia, and peripheral neuropathies. As outlined in the proposal, the XF-96 analyzer will allow the investigators to measure mitochondrial function in whole neuronal and glial cell populations over time eliminating the need for timed experiments with multiple samples at different time points; thus expediting the research and facilitating explorations of new scientific directions. PUBLIC HEALTH RELEVANCE: The proposed purchase of Seahorse XF96 analyzer will help expedite ongoing studies aimed at understanding the mechanisms of a variety of neurodegenerative diseases, including dementias, motor neuron disease, multiple sclerosis and peripheral neuropathies. These neurodegenerative diseases are among the most common and devastating types of neurological disorders affecting a large segment of the population.

描述（由申请人提供）：线粒体在许多神经系统疾病的发病机理中起关键作用，部分原因是线粒体在突触和轴突沿着神经元活动中的独特功能。已经开发了使用原发性神经元培养物，外植体/切片培养物以及神经元和神经胶质细胞系的神经退行性疾病的体外模型，以研究疾病机制并建立药物筛查的测定法。线粒体在这些体外模型中正在研究线粒体在氧化应激，轴突变性，细胞死亡和神经元能源代谢中的作用，但是大多数当前可用的测定方法都有局限性。线粒体功能的许多测定法需要从细胞中分离线粒体，从而消除细胞内信号传导对线粒体功能的贡献。其他测定是间接的，并查看线粒体功能障碍的后果，通常是静态测定。一种在神经元和神经胶质细胞内实时评估线粒体功能的仪器将具有很大的价值，可以在神经退行性疾病发病机理中对线粒体相关性进行假设具有很高的价值。 Seahorse XF-96分析仪是一种仪器，允许人们实时评估活细胞中活细胞中的氧气消耗率（OCR）和细胞外酸化速率（ECAR，即质子产生）。拟议的XF-96的主要研究者和主要使用者是所有研究神经退行性疾病机制的神经科学家和神经科学家，包括运动神经元疾病，多发性硬化症，人类免疫缺陷病毒（HIV）痴呆症和周围神经性神经病。如该提案中概述的那样，XF-96分析仪将允许研究人员在整个神经元和神经胶质细胞种群中测量线粒体功能，从而消除了在不同时间点使用多个样本的定时实验的需求；从而加快了研究并促进新科学方向的探索。 公共卫生相关性：拟议购买Seahorse XF96分析仪将有助于加快正在进行的研究，以了解各种神经退行性疾病的机制，包括痴呆症，运动神经元，多发性硬化症和周围神经病。这些神经退行性疾病是影响大部分人群的最常见和破坏性的神经系统疾病。