Chemosensation of death conspecifics modulates neural signaling and lifespan in Caenorhabditis elegans

死亡同种的化学感受调节秀丽隐杆线虫的神经信号和寿命

• 批准号: 10553123
• 负责人: Mirella Hernandez
• 金额: $ 2.22万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-05-01 至 2023-09-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10553123
• 关键词: Address; Adult; Affect; Afferent Neurons; Aging; Animals; Behavior; Behavioral; Biological; Caenorhabditis elegans; Calcium; Calcium Channel; Cessation of life; Cues; Data; Detection; Environment; Esthesia; Exposure to; Foundations; Functional Imaging; Future; G Protein-Coupled Receptor Signaling; G-Protein-Coupled Receptors; GTP-Binding Proteins; Genetic; Goals; Guanylate Cyclase; Head; Health; Hermaphroditism; Human; Image; Interneurons; Invertebrates; Knowledge; Length; Longevity; Mammals; Mediating; Membrane; Mentors; Modeling; Molecular; Monitor; Motor Neurons; Nematoda; Nervous System; Neurons; Neurotransmitters; Output; Perception; Perfusion; Physiological; Positioning Attribute; Process; Publishing; Quality of life; RNA Interference; Regulation; Research; Role; Sensory; Signal Pathway; Signal Transduction; Taxes; Translating; Vanilloid; Work; avoidance behavior; cyclic-nucleotide gated ion channels; design; experimental study; follow-up; genetic approach; healthspan; imaging approach; improved; insight; mutant; negative affect; neural circuit; neuromechanism; neurotransmission; new therapeutic target; novel strategies; receptor; response; sensory integration; sensory system; therapy development

PROJECT ABSTRACT All animals rely on sensory systems to detect and respond to environmental and behavioral cues. In most animals, this sensory information is perceived and processed by different sensory neurons, allowing animals to respond appropriately to maximize health- and lifespan. However, a detailed understanding of the underlying cues and mechanisms by which the sensory nervous system regulates lifespan and aging remains largely unknown. Addressing these gaps in knowledge is imperative to obtain a comprehensive understanding of the impact of sensory perception on lifespan regulation. The goal of my project is to identify the neurons and signaling mechanisms by which the perception of dead conspecifics regulates behavior and lifespan in Caenorhabditis elegans. My preliminary work using C. elegans shows that exposure to dead conspecifics result in 1) aversive behavior and 2) shortened lifespan. My studies also suggest that dead conspecifics release “death cues” that are detected by olfactory neurons. My central hypothesis is that detection of intracellular metabolites released by dead conspecifics are recognized by amphid olfactory neurons AWB and/or ASH, promoting a GPCR-dependent signaling cascade leading to the observed aversive behavior and lifespan shortening. The objective of Aim 1 is to identify the sensory, inter-, and motor neurons required and sufficient for death perception in C. elegans. Aim 2 will define the molecular mechanisms translating death perception to behavioral changes and shortened lifespans. The proposed research will provide new fundamental knowledge into the role of sensory perception in the regulation of aging. This may represent the first step towards uncovering novel therapeutic targets capitalizing on the sensory perception – aging relationship.

项目摘要 所有动物都依靠感官系统来检测环境和行为线索并做出反应。在大多数 动物，这种感觉信息由不同的感觉神经元感知和处理，允许动物 适当地应对，以最大限度地提高健康和寿命。然而，详细了解潜在的 感官神经系统调节寿命和衰老的线索和机制在很大程度上仍然存在 未知。解决这些知识上的差距是全面理解 感觉知觉对寿命调节的影响。我这个项目的目标是识别神经元和 死亡同种异物的感知调节动物行为和寿命的信号机制 秀丽隐杆线虫。我对线虫的初步研究表明，接触死亡的共生生物 导致1)厌恶行为和2)寿命缩短。我的研究还表明，死亡的同种 释放被嗅觉神经元探测到的“死亡信号”。我的中心假设是检测到 双目嗅觉神经元AWB识别死亡同种异体释放的细胞内代谢物 和/或ASH，促进依赖于GPCR的信号级联导致观察到的厌恶行为和 寿命缩短。目标1的目标是确定所需的感觉、中间和运动神经元以及 足以感知线虫的死亡。目标2将定义翻译死亡的分子机制 对行为变化和寿命缩短的感知。拟议的研究将提供新的 了解感官知觉在调节衰老中的作用的基础知识。这可能代表 利用感官知觉发现新治疗靶点的第一步--衰老 两性关系。