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制中发挥着关键作用，部分原因是线粒体在突触和沿轴突的神经元活动中具有独特的功能。利用原代神经元培养物、外植体/切片培养物以及神经元和神经胶质细胞系开发了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选方法。线粒体在氧化应激、轴突变性、细胞死亡和神经元能量代谢中的作用正在这些体外模型中进行研究，但大多数目前可用的检测方法都有局限性。许多线粒体功能测定需要将线粒体与细胞分离，消除细胞内信号传导对线粒体功能的影响。其他测定是间接的，着眼于线粒体功能障碍的后果，并且通常是静态测定。实时评估神经元和神经胶质细胞内线粒体功能的仪器对于检验线粒体在神经退行性疾病发病机制中相关性的假设具有重要价值。 Seahorse XF-96分析仪就是这样一种仪器，可以实时评估活细胞中的耗氧率（OCR）和细胞外酸化率（ECAR，即质子产生）。拟议的XF-96的主要研究者和主要用户都是研究神经退行性疾病机制的神经学家和神经科学家，包括运动神经元疾病、多发性硬化症、人类免疫缺陷病毒（HIV）痴呆和周围神经病。正如提案中所述，XF-96 分析仪将允许研究人员随着时间的推移测量整个神经元和神经胶质细胞群的线粒体功能，从而无需在不同时间点对多个样本进行定时实验；从而加快研究速度并促进新科学方向的探索。 公共健康相关性：拟议购买 Seahorse XF96 分析仪将有助于加快正在进行的研究，旨在了解各种神经退行性疾病的机制，包括痴呆、运动神经元疾病、多发性硬化症和周围神经病。这些神经退行性疾病是影响很大一部分人群的最常见和最具破坏性的神经系统疾病类型。