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

项目摘要 年龄相关性嗅觉衰退(老年性嗅觉衰退)广泛存在于许多物种中，包括人类。至少 一千五百万55岁以上的美国人患有老花眼。通过影响幸福，生活质量， 总体而言，老年痴呆症对公共卫生构成了重大挑战。老年性嗅觉障碍患者 经常表现出对食物的兴趣下降，可能会退出社交，并表现出更高的抑郁率。 此外，包括帕金森氏症和阿尔茨海默病在内的许多与年龄有关的神经疾病， 通常与嗅觉功能障碍有关。事实上，嗅觉丧失往往先于各种机动车 这些致命的神经系统疾病的症状。尽管嗅觉对人类生理学和 健康，老年性嗅觉的细胞和分子机制知之甚少(知识 Gap)。 作为神经系统的一种主要细胞类型，神经胶质细胞通常被认为是被动的调节器。 神经发育和突触传递。神经胶质细胞在感觉转导中是否发挥积极作用 而且，人们对大脑老化的了解还不够深入。线虫是一种公认的神经科学和 衰老研究由于其简单的神经系统，短的寿命，和强大的遗传工具。非常重要的是， 来自多个模式生物的遗传学研究表明，进化上保守的遗传程序 而信号通路在调节跨物种的感觉转导和衰老过程中起着关键作用。 这项提议将把体内钙成像、光遗传学、分子遗传学和行为学结合起来。 分析研究和发现嗅神经胶质细胞发挥作用的分子机制 在气味检测和年龄相关性嗅觉衰退中发挥积极作用。因为嗅觉和衰老都是 在进化保守的基因和信号通路的调控下，我们对线虫的创新性研究 嗅觉和年龄相关性嗅觉衰退中的神经胶质细胞将为类似的 在其他物种中的过程。

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.