EXPERIMENTAL, CLINICAL AND MODELING STUDIES OF HUMAN OLFACTORY ADAPTATION

人类嗅觉适应的实验、临床和建模研究

• 批准号: 6651285
• 负责人: PAMELA HELEN DALTON
• 金额: $ 26.25万
• 依托单位: MONELL CHEMICAL SENSES CENTER
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6651285
• 关键词: age difference; behavioral /social science research tag; biological transport; chemoreceptors; clinical research; environmental adaptation; human old age (65+); human subject; mathematical model; model design /development; odors; olfactions; olfactory disorder; olfactory stimulus; olfactory threshold

The overall goal of this project is to describe the variation in the dynamics of olfactory adaptation and recovery, and to relate the contribution of per-receptor mechanisms involved in odorant transport and clearance to this variation. The proposed research will pursue this goal through experimental and clinical studies aimed at elucidating the range and sources of variation in adaptation, and by developing a mathematical model of olfactory adaptation to serve as a unifying framework. The three specific aims of the proposed research are: (1) to evaluate the extent to which peri-receptor processes involved in odorant transport and clearance can modulate the time-course of adaptation and recovery, (2) to characterize the variation in the dynamic response of a challenged olfactory system as a function and clinical etiology and age, especially among clinic patients who report rapid and prolonged adaptation to ambient and food-mediated odors, and (3) to develop a mathematical transport model of olfactory adaptation capable of simulating the odorant transport, accumulation and clearance in the nasal/olfactory region, and if appropriate, the time-course of receptor adaptation and recovery (as measured in Project 1). This project will increase our understanding of the role of peri-receptor events in the development of both short- and long-term adaptation and recovery. Moreover, through interactions with Project 4 in this CCRC we will obtain a better understanding of the relationship between receptor and peri-receptor events in adaptation. The project has important implications for efforts to remediate dynamic olfactory loss in real world situations. Although rapid adaptation is frequently reported in clinical evaluations, current clinical assessments of olfactory dysfunction do not include tests that measure rates of adaptation and recovery. However, abnormal rates of adaptation or recovery could significantly diminish olfactory sensitivity, as well as render individuals more vulnerable to hazards such as gas leaks, fires and spoiled food. Aberrant adaptation and/or recovery could also contribute to nutritional problems by reducing the perception and enjoyment of food. Peri-receptor mechanisms that contribute significantly to dynamic olfactory loss may be amenable to therapeutic interventions for restoring certain aspects of olfactory function.

该项目的总体目标是描述嗅觉适应和恢复动力学的变化，并将涉及气味转运和清除涉及的环的机制的贡献与这种变化相关联。拟议的研究将通过旨在阐明适应性变化的范围和来源的实验和临床研究来追求这一目标，并通过开发嗅觉适应性的数学模型以作为统一的框架。拟议的研究的三个具体目的是：（1）评估与气味运输和清除相关的受感受器的过程的程度可以调节适应和恢复的时间顺序，（2）以表征有挑战性的嗅觉系统的动态反应的变化，是一种功能和临床病因，尤其是在临床上和临床中的临床和进化，以及（以及（临床），以及（以及（临床上），以及（以及（临床上），以及（以及（逐渐发展），以及（以及（又是），（并逐渐发展）和（偶发）的偶发和（偶发）偶发的偶发性（偶发）和（偶发）偶发的偶发性异常。嗅觉适应性的数学转运模型，能够模拟鼻/嗅觉区域中的气味转运，积累和清除，如果适当的话，受体适应性和恢复的时间顺序（如项目1中所述）。该项目将增加我们对受体周期事件在短期和长期适应和恢复发展中的作用的理解。此外，通过与该CCRC项目4的相互作用，我们将更好地理解适应中受体和受体周期事件之间的关系。该项目对在现实世界情况下为动态嗅觉损失的努力具有重要意义。尽管在临床评估中经常报告快速适应，但是当前对嗅觉功能障碍的临床评估不包括测量适应和恢复速率的测试。但是，适应或恢复率异常可能会显着降低嗅觉敏感性，并使个人更容易受到危害，例如气体泄漏，火灾和宠坏食物。异常适应和/或恢复也可能通过减少食物的感知和享受来导致营养问题。受体周围的机制对动态嗅觉损失产生了重大贡献，可能与治疗性干预措施可以恢复嗅觉功能的某些方面。