权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Neurotoxic Effects of Volatile Anesthetics in C. elegans

挥发性麻醉剂对秀丽隐杆线虫的神经毒性作用

基本信息

批准号：
8235788
负责人：
PHILIP G MORGAN
金额：
$ 24.38万
依托单位：
SEATTLE CHILDREN'S HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-07-01 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8235788
关键词：
Adult Age-Years Anesthesiology Anesthetics Animal Model Animals Apoptosis Apoptotic Behavioral Assay Belief Benign Birth Brain Caenorhabditis elegans Cell Death Cells Cellular Membrane Chemotaxis Child Data Defect Development Event Exposure to General Anesthesia Genes Genetic Genetic Models Genome Grant Homologous Gene Human Hypersensitivity Infant Infant Care Investigation Isoflurane Laboratories Learning Libraries Life Mammals Measures Memory Methods Mitochondrial Membrane Protein Molecular Molecular Target Mutation Nematoda Nerve Degeneration Nervous system structure Neuraxis Pathway interactions Pharmaceutical Preparations Phylogeny Predisposition Process Proteins RNA Interference Rattus Research Research Design Risk Rodent Screening procedure Techniques Testing Work genome-wide high risk inhibitor/antagonist neonatal exposure neurotoxic neurotoxicity novel prevent public health relevance response synaptogenesis

项目摘要

DESCRIPTION (provided by applicant): Since their inception, volatile anesthetics have been thought to be benign inhibitors of the central nervous system. However, recent studies have seriously challenged this dogma, and caused a startling paradigm shift in the field of anesthesiology, in particular in regard to the care of infants undergoing general anesthesia. Volatile anesthetics have now been shown to cause apoptotic neuronal degeneration in developing rat brains. Preliminary data indicate that this effect is likely to exist in humans as well. As we show in our preliminary data (see Research Design), we have established a similar effect in the model organism, C. elegans. In this proposal we will identify genes responsible for the initiation of neurotoxicity following anesthetic exposure in the developing nervous systems. To accomplish this we will screen a genome wide RNAi library from the nematode, C. elegans. These genes will be tested for their ability to regulate anesthetic induced neurotoxicity. We hypothesize that significant discoveries of novel, previously unsuspected molecular targets that initiate neuronal degeneration will be identified in the nematode, and that they will be predictive of similar functionally significant responses in mammals. Available data support the belief that interactions leading to apoptosis will be maintained at a high level when studied across phylogeny. We hypothesize that identification of the genes which control anesthetic induced neurotoxicity will target molecules that can inhibit this phenomenon and guide research for safer anesthetic exposure in children. PUBLIC HEALTH RELEVANCE: Volatile anesthetics have been shown to induce neurotoxicity in the central nervous system of several mammalian species, possible including humans. Little is known about how this neurotoxic effect is initiated. We propose to identify the genes important in this response using a genetic approach in the nematode, C. elegans.

描述（由申请人提供）：挥发性麻醉药自问世以来一直被认为是中枢神经系统的良性抑制剂。然而，最近的研究已经严重挑战了这一教条，并在麻醉学领域引起了惊人的范式转变，特别是在接受全身麻醉的婴儿的护理方面。挥发性麻醉剂现在已被证明会导致发育中的大鼠大脑中的凋亡神经元变性。初步数据表明，这种效应可能也存在于人类中。正如我们在初步数据中所显示的那样（见研究设计），我们已经在模式生物C.优雅的在这个提议中，我们将确定在发育中的神经系统中麻醉剂暴露后引起神经毒性的基因。为了实现这一点，我们将从线虫C.优雅的将检测这些基因调节麻醉剂诱导的神经毒性的能力。我们假设，重大发现的新的，以前未被怀疑的分子靶点，启动神经元变性将被确定在线虫，他们将预测类似的功能显着的反应在哺乳动物。现有的数据支持这样的信念，即导致细胞凋亡的相互作用将保持在一个高水平时，跨胚胎发育研究。我们假设，控制麻醉剂诱导的神经毒性的基因的鉴定将靶向分子，可以抑制这种现象，并指导研究更安全的麻醉剂暴露在儿童。公共卫生相关性：挥发性麻醉剂已被证明可诱导几种哺乳动物（可能包括人类）中枢神经系统的神经毒性。人们对这种神经毒性作用是如何产生的知之甚少。我们建议在线虫C.优雅的