Mechanistic studies of sickness sleep

病态睡眠的机制研究

• 批准号: 10630175
• 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/10630175
• 关键词: Acceleration; Address; Adult; Affect; Afferent Neurons; 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; Invertebrates; Mammals; Methods; Motivation; Movement; Mus; Mutagenesis; Mutagens; 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; Vertebrates; Viral; Virus Diseases; Withdrawal; arm; candidate identification; cytokine; deprivation; environmental stressor; feeding; fly; gene function; gene product; genetic manipulation; genome-wide; interest; mortality; mutant; paracrine; prevent; programs; sleep behavior; 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.

项目概要 与其他动物一样，在线虫中，疾病与运动减少、活动减少有关。 喂养，增加睡眠。蠕虫的疾病行为是由环境压力引起的，包括 热休克、紫外线和感染。生病期间的这种行为程序是由蠕虫调节的 被细胞因子表皮生长因子（EGF）激活的中枢神经元。 EGF 导致活性降低 在蠕虫、苍蝇、鱼和小鼠中，EGF 激活本身的机制尚不清楚。我们 将利用秀丽隐杆线虫来研究疾病期间EGF的调节机制。在目标 1 中，我们将确定 EGF 在何处（从哪些细胞）以及何时释放以促进疾病行为。确定其他监管机构 EGF 激活的过程，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，我们将检验疾病行为支持疾病期间生存的假设。沿着- 这些研究的长期目标是确定用于开发诊断和治疗的候选信号分子 治疗生病期间的嗜睡并了解睡眠对促进康复的重要性 来自疾病。