Optoanesthesia

光麻醉

基本信息

批准号：
9113968
负责人：
Max Kelz
金额：
$ 30.91万
依托单位：
UNIVERSITY OF PENNSYLVANIA
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9113968
关键词：
Address Adverse effects Affinity Agonist Anesthesia procedures Anesthetics Animals Arousal Behavioral Binding Binding Proteins Binding Sites Biochemistry Brain Brain Stem Brain region Cell Fractionation Cell Nucleus Cells Clinical Cross-Linking Reagents Data Development Drug effect disorder Drug usage Electroencephalography Electrophysiology (science)General anesthetic drugs Health Hypnosis Hypothalamic structure Individual Injectable Injection of therapeutic agent Knowledge Lasers Life Light Lighting Maps Mass Spectrum Analysis Membrane Methods Mining Molecular Molecular Target Mus Neurobiology Neurons Operative Surgical Procedures Pharmaceutical Preparations Pharmacology Photochemistry Physicians Physiological Procedures Process Propofol Proteins Proteome Proteomics Publishing Recovery Resolution Rodent Series Signal Transduction Site Sleep Slice Swelling System Tadpoles Tail Techniques Thalamic structure Therapeutic Tissue Harvesting Unconscious State Validation Veins Work adduct analog base brain tissue cell type design drug efficacy frontal lobe hypnotic improved in vivo indexing locus ceruleus structure multidisciplinary neuronal circuitry novel novel strategies photoactivation preoptic nucleus

项目摘要

DESCRIPTION (provided by applicant): The alkylphenol anesthetic propofol is used in millions of surgical and noxious procedures annually. While the clinical use of propofol has swelled, mechanistic understanding of its many actions, on all levels, has lagged behind. In this proposal, we will deploy our photoactive alkylphenol analogues of propofol, azi-propofol-m (aziPm) and 2-propynloxymethoxy-5-trifluoromethyldiazirinylphenol (aziPm-click), in a tiered series of studies to reveal: the photoactive alkylphenol binding proteome using state-of-the-art mass spectrometry and enrichment methods (aim 1), the electro- physiological character of photoactive alkylphenols in discrete nuclei in brain slices (aim 2), and the in-vivo contribution o individual cells and networks to the hypnotic effects of alkylphenols. These latter studies will us fiberoptic laser stimulation of discrete regions of brain in live mice after systemic administratio of photoactive alkylphenols (aim 3). The three aims are integrated by their common prediction of molecular substrates arising from very different, complimentary and unbiased approaches. These studies will result in the identification of novel and plausible molecular substrates for alkylphenol action, which will serve as the basis for validation in subsequent proposals involving the construction of genetically altered animals. This collaborative project is ideally suited to integrate the neurobiological expertise of the Kelz lab with the electrophysiologic mastery of the Beck lab, and the biological chemistry prowess of the Eckenhoff and Dailey labs.

描述（由申请人提供）：烷基苯酚麻醉丙泊酚每年用于数百万手术和有害程序中。尽管丙泊酚的临床使用膨胀了，但机械理解其在各个层面上的许多作用都落后了。在这项建议中，我们将部署丙泊酚，Azi-Propopofol-M（Azipm）和2-丙氧基甲氧化物-5-三氧基5-三氧基甲基二氮杂烯醇酚（Azipm-click）的光活性烷基苯酚类似物（Azipm-click），在一系列研究中，可以揭示出一系列型号的蛋白质，以揭示出层次的型号。光谱和富集方法（AIM 1），脑切片中离散核中光活性烷基苯酚的电生理特征（AIM 2），以及维沃的含量o单个细胞和网络对烷基苯酚的催眠作用的网络和网络。这些后者的研究将在全身施用光活性烷基苯酚后，我们将在活小鼠中对活小鼠的离散区域的光纤激光刺激（AIM 3）。这三个目标是由它们对分子底物的共同预测进行了整合，这些预测是由非常不同，免费和公正的方法引起的。这些研究将导致对烷基苯酚作用的新颖和合理的分子底物鉴定，这将是随后涉及涉及基因动物构建的提案中验证的基础。该协作项目非常适合将KELZ实验室的神经生物学专业知识与贝克实验室的电生理掌握以及Eckenhoff和Dailey Labs的生物化学能力相结合。