Active roles of glial cells in olfaction and age-related olfactory decline

神经胶质细胞在嗅觉和年龄相关嗅觉衰退中的积极作用

• 批准号: 10672267
• 负责人: Rui Xiao
• 金额: $ 30.67万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10672267
• 关键词: Affect; Afferent Neurons; Age; Aging; Alzheimer' s Disease; American; Anabolism; Anosmia; Behavioral; Biological; Caenorhabditis elegans; Calcium; Cells; Data; Detection; Disease Vectors; Endowment; Exhibits; Food; GABA Receptor; Genetic; Genetic study; Health; Human; ITPR1 gene; Image; Knowledge; Label; Logic; Longevity; Mammals; Mediating; Mental Depression; Modeling; Molecular; Molecular Genetics; Nematoda; Nervous System; Neuroglia; Neurons; Neurosciences; Odors; Olfactory Pathways; Olfactory Receptor Cells; Olfactory dysfunction; Parkinson Disease; Patients; Peripheral; Personal Satisfaction; Physiological; Physiology; Play; Process; Public Health; Quality of life; Research; Role; Sensory; Series; Signal Pathway; Signal Transduction; Signaling Molecule; Smell Perception; Supporting Cell; Symptoms; Synaptic Transmission; TRPV channel; Testing; Time; age related; aging brain; avoidance behavior; cell type; experimental study; functional decline; gamma-Aminobutyric Acid; gene conservation; in vivo; in vivo calcium imaging; innovation; insight; interest; model organism; mutant; nervous system disorder; neurodevelopment; neuroprotection; novel; olfactory sensory neurons; optogenetics; programs; receptor; social; sustentacular cell; tool; transmission process

Project Summary Age-dependent olfactory decline (presbyosmia) is widely present in many species, including humans. At least fifteen million Americans over 55 years old suffer from presbyosmia. By affecting the well-being, quality of life, and overall health, presbyosmia presents a significant challenge to public health. Patients with presbyosmia often show a decreased interest in food, can withdraw socially, and exhibit higher rates of depression. Furthermore, many age-related neurological diseases, including Parkinson's disease and Alzheimer's disease, are commonly associated with olfactory dysfunction. In fact, olfactory loss often precedes various motoric symptoms in these deadly neurological diseases. Despite the importance of olfaction to human physiology and health, the cellular and molecular mechanisms underlying presbyosmia are poorly understood (knowledge gap). As a major cell type in the nervous system, glial cells are typically considered as passive modulators during neural development and synaptic transmission. Whether glial cells play active roles in sensory transduction and brain aging is not well understood. C. elegans is a well-established model organism for neuroscience and aging research due to its simple nervous system, short lifespan, and powerful genetic tools. Very importantly, genetic studies from multiple model organisms have shown that the evolutionarily conserved genetic programs and signaling pathways play pivotal roles in regulating sensory transduction and aging process across species. This proposal will bring together in vivo calcium imaging, optogenetics, molecular genetics, and behavioral analysis to investigate and discover the molecular mechanisms through which the olfactory glial cells play active roles in odorant detection and age-dependent olfactory decline. Since both olfaction and aging are regulated by the evolutionarily conserved genes and signaling pathways, our innovative studies on C. elegans glial cells in olfaction and age-associated olfactory decline will provide mechanistic insights into similar processes in other species.

项目概要 年龄依赖性嗅觉衰退（老嗅觉）广泛存在于许多物种中，包括人类。至少 55 岁以上的美国人有 1500 万患有老花眼症。通过影响福祉和生活质量， 和整体健康而言，老花症对公共卫生提出了重大挑战。老花眼患者 经常表现出对食物的兴趣下降、社交退缩，并且抑郁症发病率较高。 此外，许多与年龄相关的神经系统疾病，包括帕金森病和阿尔茨海默病， 通常与嗅觉功能障碍有关。事实上，嗅觉丧失往往先于各种运动能力丧失。 这些致命的神经系统疾病的症状。尽管嗅觉对人体生理学很重要 健康方面，人们对老花症背后的细胞和分子机制知之甚少（知识 差距）。 作为神经系统中的主要细胞类型，神经胶质细胞通常被认为是神经系统中的被动调节剂。 神经发育和突触传递。胶质细胞是否在感觉转导中发挥积极作用 大脑衰老尚不清楚。线虫是一种成熟的神经科学模型生物 衰老研究因其简单的神经系统、较短的寿命和强大的遗传工具而受到关注。非常重要的是， 对多种模式生物的遗传学研究表明，进化上保守的遗传程序 信号通路在调节跨物种的感觉转导和衰老过程中发挥着关键作用。 该提案将结合体内钙成像、光遗传学、分子遗传学和行为学 分析以研究和发现嗅觉神经胶质细胞发挥作用的分子机制 在气味检测和年龄依赖性嗅觉衰退中发挥积极作用。由于嗅觉和衰老都是 受进化上保守的基因和信号通路的调节，我们对线虫的创新研究 神经胶质细胞在嗅觉和与年龄相关的嗅觉下降中的作用将为类似的机制提供见解 其他物种的过程。