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 所有动物都依靠感觉系统来检测和响应环境和行为提示。大多数 动物，这种感官信息是由不同的感觉神经元感知和处理的，使动物能够 适当地回应最大化健康和寿命。但是，对基础的详细理解 感觉神经系统调节寿命和衰老的提示和机制在很大程度上保持 未知。在Knowle中解决这些差距必须获得对 感觉知觉对寿命调节的影响。我项目的目的是确定神经元和 信号传导机制通过这种机制来调节行为和生命周期的感知 秀丽隐杆线虫。我使用秀丽隐杆线虫的初步工作表明，暴露于死去的概念 导致1）厌恶行为和2）缩短寿命。我的研究还表明死去的概念 释放嗅觉神经元检测到的“死亡线索”。我的中心假设是检测 死亡概念发布的细胞内代谢产物被两层嗅觉神经元AWB认可 和/或灰烬，促进依赖GPCR的信号传导级联反应，导致观察到的厌恶行为和 寿命缩短。目标1的目的是确定所需的感觉，间和运动神经元，并且 AIM 2将定义翻译死亡的分子机制 对行为改变和寿命缩短的感知。拟议的研究将提供新的 感官感知在调节衰老中的作用的基本知识。这可能代表 迈向迈向感官感知的新型治疗目标 - 衰老的第一步 关系。