Mechanistic studies of sickness sleep

病态睡眠的机制研究

• 批准号: 10274876
• 负责人: David Menassah Raizen
• 金额: $ 40.63万
• 依托单位: UNIVERSITY OF PENNSYLVANIA
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-15 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10274876
• 关键词: Address; Adult; Affect; Afferent Neurons; African Trypanosomiasis; Animals; Auxins; Behavior; Behavior Control; Behavioral; Biological; Biological Models; Caenorhabditis elegans; Cells; Cellular Stress; Chemicals; Chronic; Clinical Treatment; Data; Defect; Diagnostic; Drowsiness; Epidermal Growth Factor; Epidermal Growth Factor Receptor; Fishes; Functional disorder; Future; Genes; Genetic; Genetic Transcription; Goals; Heat-Shock Response; Human; Impairment; Infection; Inflammatory; Life; Mammals; Methods; Motivation; Movement; Mus; Mutagenesis; Mutate; Mutation; Nematoda; Neurons; Neurosecretory Systems; Peptides; Peripheral; Positioning Attribute; Receptor Signaling; Recovery; Regulation; Signal Transduction; Signaling Molecule; Site; Sleep; Sleep Deprivation; Source; Stream; Stress; Symptoms; System; Testing; Time; Translating; Ultraviolet Rays; Uncertainty; Viral; Virus Diseases; Withdrawal; arm; cytokine; deprivation; environmental stressor; feeding; fly; gene function; gene product; genetic manipulation; genome-wide; interest; mortality; mutant; paracrine; prevent; programs; social; tool; whole genome

Project Summary In the nematode C. elegans as in other animals, sickness is associated with reduced movement, reduced feeding, and increased sleep. Sickness behavior in worms is induced by environmental stressors including heat shock, ultraviolet light, and infection. This behavioral program during sickness is regulated by worm central neurons that are activated by the cytokine epidermal growth factor (EGF). EGF causes reduced activity in worms, flies, fish, and mice, but the mechanisms of EGF activation itself during sickness are not clear. We will use C. elegans to study the mechanism of EGF regulation during sickness. In Aim 1, we will determine where (from which cells) and when EGF is released to promote sickness behavior. To identify other regulators of EGF activation, in Aim 2, we will perform genome-wide discovery screens for genes required for sickness behavior. In Aim 3, we will test the hypothesis that sickness behavior supports survival during sickness. A long- term goal of these studies is to identify candidate signaling molecules for developing diagnostics and treatments of sleepiness during sickness and to understand the importance of sleep in promoting recovery from illness.

项目摘要 线虫C.与其他动物一样，疾病与运动减少有关， 饮食，增加睡眠。蠕虫的疾病行为是由环境应激因素引起的，包括 热休克紫外线和感染这种疾病期间的行为程序是由蠕虫控制的 由细胞因子表皮生长因子（EGF）激活的中枢神经元。EGF会降低活性 在蠕虫、苍蝇、鱼和小鼠中，EGF的活性是非常高的，但在疾病期间EGF本身的激活机制尚不清楚。我们 将使用C。研究EGF在疾病中的调节机制。在目标1中，我们将确定 EGF是什么时候释放出来的？EGF是什么时候释放出来的？确定其他监管机构 在目标2中，我们将对疾病所需的基因进行全基因组发现筛选， 行为在目标3中，我们将检验患病行为支持患病期间生存的假设。很长的- 这些研究的长期目标是鉴定用于开发诊断的候选信号分子， 治疗疾病期间的嗜睡，并了解睡眠在促进恢复的重要性 因为生病