The Neurometabolome of a Sensory Neuronal Network

感觉神经网络的神经代谢组

• 批准号: 7878517
• 负责人: Jonathan V. Sweedler
• 金额: $ 32.34万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-08-15 至 2012-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7878517
• 关键词: Address; Adverse effects; Afferent Neurons; Area; Axon; Biochemistry; Biological; Biological Markers; Biological Models; Blood capillaries; Brain; Capillary Electrophoresis; Cell Communication; Cells; Cellular Structures; Chemical Stimulation; Chemicals; Collection; Complement; Coupled; Dendrites; Detection; Development; Diagnosis; Disease; Fluorescence; Fourier Transform; Future; Goals; Grant; Health; Heterogeneity; Individual; Inflammation; Investigation; Knowledge; Lasers; Lead; Location; Mass Spectrum Analysis; Measurement; Measures; Methodology; Methods; Modeling; Morphology; Motivation; Nature; Nerve Tissue; Nervous system structure; Neurons; Neurotransmitters; Nociception; Nutrient; Outcome; Pain; Pathway interactions; Peptides; Principal Investigator; Property; Regulation; Research; Resolution; Role; Sampling; Sensory; Site; Spinal Ganglia; Spinal nerve structure; Staging; Structure; Supporting Cell; Techniques; Technology; Testing; Tissues; Variant; Work; base; biological systems; body system; capillary; career; cell type; ganglion cell; improved; inflammatory pain; innovation; metabolomics; nanolitre; neuronal cell body; novel; novel strategies; programs; research study; small molecule; spinal nerve posterior root

DESCRIPTION (provided by applicant): Understanding the healthy and the diseased brain requires knowledge of the biochemistry occurring within the neurons and supporting cells that make up our brain. It is well known that individual cells in the nervous system have distinct protein complements, but the consequences of this heterogeneity on the cellular metabolome are much less well understood. While neurotransmitters used in a network vary neuron-by-neuron, what are the cell-to-cell variations of the metabolome in the mammalian nervous system? For most metabolites, the answer is unknown. Using a suite of analytical technologies based on small-volume sampling, capillary electrophoresis with laser- induced fluorescence detection, single cell mass spectrometry, and capillary separations coupled to Fourier-transform mass spectrometry, the neurometabolome of a network of dorsal root ganglion (DRG) sensory neurons will be studied with unmatched chemical detail. DRG neurons are involved in the mechanisms of pain - one of most devastating side effects of many disorders. The neurotransmitters and metabolites in individual neurons and their functional neuronal compartments such as dendrites, axons, and cell bodies, will be characterized. The first stage of this work is to compile information on the metabolome of the DRG neurons, and examine this for unusual molecules. Next, using the DRG and its neurometabolome as the model, several specific questions are addressed: (1) Does the neurometabolome of functionally distinct neuronal compartments differ? (2) What subset of the small-molecule complement is released upon electrical or chemical stimulation, and thus may participate in cell-to-cell communication? (3) How does inflammation- induced pain change the neurometabolome of the DRG neurons? These efforts fit within the scope of the metabolomics roadmap initiative by developing innovative methodologies to investigate neurotransmitter and other small molecule compartmentalization on the function of a model sensory neuron network.

描述（由申请人提供）：了解健康和患病的大脑需要了解神经元内发生的生物化学以及构成我们大脑的细胞。众所周知，神经系统中的单个细胞具有不同的蛋白质补体，但是这种异质性对细胞代谢组的后果知之甚少。尽管在网络中使用的神经递质变化为神经元，但哺乳动物神经系统中代谢组的细胞间变化是什么？对于大多数代谢产物，答案是未知的。使用基于小体积抽样的一套分析技术，具有激光诱导的荧光检测的毛细管电泳，单细胞质谱法和毛细管分离与傅立叶转换质谱法耦合，该质谱法的神经元代谢组，与DRESANGLION NEURONS网络的Neururometome（DRED GRANDION NEURONS）的Never neurons进行了研究。 DRG神经元参与疼痛的机制 - 许多疾病的最具破坏性的副作用之一。将表征单个神经元中的神经递质和代谢物及其功能性神经元室（例如树突，轴突和细胞体）。这项工作的第一阶段是汇编有关DRG神经元代谢组的信息，并检查它是否异常分子。接下来，将DRG及其神经代谢组作为模型，解决了几个特定问题：（1）功能上不同的神经元区室的神经态量代谢组是否有所不同？ （2）在电或化学刺激时释放了哪些小分子补体子集，因此可能参与细胞对细胞通信？ （3）炎症引起的疼痛如何改变DRG神经元的神经量代谢组？这些努力通过开发创新的方法来研究神经递质和其他小分子隔室化，以了解模型感觉神经元网络的功能来研究代谢组学路线图计划的范围。