In vivo investigation of mitochondrial dynamics in the mouse brain

小鼠大脑线粒体动力学的体内研究

• 批准号: 8869236
• 负责人: Tommy L Lewis
• 金额: $ 9.5万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-15 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8869236
• 关键词: Affect; Alzheimer' s Disease; Apoptosis; Axon; Biosensor; Brain; Calcium; Cells; Cephalic; Complex; Data; Dendrites; Development; Electroporation; Fluorescence-Activated Cell Sorting; Fluorescent Probes; Glucose; Head; Homeostasis; Huntington Disease; Image; Investigation; Knockout Mice; Label; Laser Scanning Microscopy; Life; Maintenance; Mass Spectrum Analysis; Measurement; Measures; Membrane Potentials; Messenger RNA; Metabolism; Methods; Microscopy; Mitochondria; Mitochondrial Proteins; Monitor; Mus; Neurodegenerative Disorders; Neurons; Organelles; Parkinson Disease; Pathway interactions; Phosphotransferases; Play; Presynaptic Terminals; Production; Proteins; Proteomics; Resolution; Rhodopsin; Role; STK11 gene; Sorting - Cell Movement; Staging; Synapses; Testing; hippocampal pyramidal neuron; imaging modality; in utero; in vivo; in vivo imaging; insight; mitochondrial membrane; neurotransmitter release; novel; novel strategies; optogenetics; postnatal; presynaptic; protein transport; public health relevance; research study; tool; trafficking; two-photon

 DESCRIPTION (provided by applicant): Neurons are highly compartmentalized cells that require unique mechanisms for trafficking proteins and organelles to their specific compartments. Mitochondria are vital organelles that regulate the levels of ATP, calcium homeostasis and apoptosis. Many neurodegenerative diseases including ALS, Huntington's, Parkinson's and Alzhemier's show a disruption of mitochondrial transport in the axon suggesting that mitochondrial localization and function must be highly regulated for the neuron to function properly. This study will develop an in vivo method for the live imaging of sparsely labeled layer 2/3 cortical neurons via 2-photon microscopy. This method will then be used to quantitate mitochondrial dynamics and presynaptic capture along axons in vivo. The role of neuronal activity will also be interrogated to determine the effect it has on mitochondrial dynamics, presynaptic capture and function. Finally, this study will develop a method for the unbiased identification of proteins unique or abundant in axonal mitochondria as compared to somato-dendritic mitochondria. The results of this study will provide new insights into the in vivo mechanisms of mitochondrial dynamics and how activity regulates their presynaptic capture and function.

 描述（由适用提供）：神经元是高度分室化的细胞，需要用于运输蛋白质和细胞器的独特机制。线粒体是调节ATP，钙稳态和凋亡水平的重要细胞器。许多神经退行性疾病包括ALS，Huntington's，Parkinson's和Alzhemier的轴突中的线粒体转运中断，这表明必须高度调节线粒体定位和功能，以使神经动物能够正常运行。这项研究将开发一种体内方法，用于通过2光子显微镜进行稀疏标记的2/3皮质神经元的实时成像。然后，该方法将用于定量沿体内轴突的线粒体动力学和突触前捕获。神经元活性的作用也将受到质疑，以确定其对线粒体动力学，突触前捕获和功能的影响。最后，这项研究将开发一种方法，以与索氏肌树突线粒体相比，在轴突线粒体中公正地鉴定蛋白质独特或丰富的蛋白质。这项研究的结果将为线粒体动力学的体内机理提供新的见解，以及活动如何调节其突触前的捕获和功能。