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: 6564032
• 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: 2002-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6564032
• 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的动态变化，并将参与气味运输和清除的前受体机制的贡献与这种变化联系起来。拟议的研究将通过旨在阐明适应变化的范围和来源的实验和临床研究来实现这一目标，并通过开发嗅觉适应的数学模型来作为统一的框架。拟议研究的三个具体目标是：（1）评价参与气味运输和清除的周围感受器过程可以调节适应和恢复的时间过程的程度，（2）表征作为功能和临床病因学和年龄的受挑战的嗅觉系统的动态响应的变化，特别是在报告对环境和食物介导的气味快速和长期适应的临床患者中，以及（3）开发能够模拟气味物传输的嗅觉适应的数学传输模型，鼻/嗅觉区域中的累积和清除，以及如果合适的话，受体适应和恢复的时间过程（如项目1中所测量的）。该项目将增加我们对受体周围事件在短期和长期适应和恢复发展中的作用的理解。此外，通过与本CCRC项目4的互动，我们将更好地了解适应中受体和受体周围事件之间的关系。该项目具有重要的意义，努力补救动态嗅觉损失在真实的世界的情况。虽然快速适应在临床评估中经常被报道，但目前嗅觉功能障碍的临床评估不包括测量适应和恢复率的测试。然而，异常的适应或恢复速度可能会大大降低嗅觉敏感性，并使个人更容易受到气体泄漏，火灾和变质食物等危险的影响。异常的适应和/或恢复也可能通过减少对食物的感知和享受而导致营养问题。周围受体机制，有助于显着的动态嗅觉损失可能是服从于治疗干预，恢复某些方面的嗅觉功能。