Degenerative Changes in the Taste System

味觉系统的退行性变化

• 批准号: 6760026
• 负责人: LYNNETTE Marie MCCLUSKEY
• 金额: $ 28.6万
• 依托单位: AUGUSTA UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-07-01 至 2008-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6760026
• 关键词: T lymphocyte; cellular immunity; computer program /software; cytokine; denervation; dietary sodium; electrodes; image processing; immunocytochemistry; inflammation; laboratory rat; leukocyte activation /transformation; leukocytes; low salt diet; macrophage; neural degeneration; neural plasticity; neuroimmunomodulation; sodium channel; taste; taste buds; vascular cell adhesion molecule

DESCRIPTION (provided by applicant): The taste system is capable of remarkable plasticity following denervation of taste receptor cells. Environmental influences at the time of nerve section play an important role in this functional plasticity. Adult rats placed on a sodium-restricted diet soon after sectioning of the chorda tympani (CT) nerve, which innervates taste receptor cells, exhibit long-lasting deficits in neurophysiological taste responses. Surprisingly, intact taste receptors also demonstrate altered taste responses within days after contralateral denervation. In fact, up-regulation of immune activity in sodium-deficient rats leads to recovery of normal taste responses in the intact CT nerve. This novel interaction between sensory and immune function was unexpected, and little is currently known about the role of the immune system in the normal or degenerating taste system. The site of changes in taste function after denervation is the amiloride-sensitive sodium channel, or ENaC, on taste receptor cells. Our long-term goal is to determine the mechanisms by which the immune system modulates ENaC function. In the current proposal, immune cells that potentially affect taste function during degeneration must first be identified. Leukocyte subtypes will be identified, counted, and their spatial relationship to denervated and intact taste buds mapped over time post-sectioning. The expression of adhesion molecules an essential signal for leukocyte entry to tissue, will be examined after denervation of taste receptor cells. Leukocyte proliferation and activation initiated by unilateral denervation of taste receptor cells will also be investigated. We hypothesize that each of these measures of immune activity is up-regulated after CT sectioning in control-fed but not sodium-restricted rats. Indeed, there is evidence that dietary sodium restriction is immunosuppressive. Finally, specific populations of leukocytes will be depleted, and the functional consequences for the degenerating taste system assessed neurophysiologically. ENaC expression will also be examined after leukocyte depletion, to determine if leukocyte regulation of the channel is a mechanism for altered sodium transduction in taste receptor cells. These experiments will provide powerful evidence for the influence of specific leukocyte populations on taste function in vivo. Proposed studies are also important for our understanding of functional interactions between neurons, sensory receptor cells, and leukocytes, and of neural plasticity after injury.

描述（由申请人提供）：味觉系统在味觉感受器细胞去神经支配后能够具有显着的可塑性。神经切断时的环境影响在这种功能可塑性中起着重要作用。成年大鼠在切断支配味觉感受器细胞的鼓索（CT）神经后不久就进行限钠饮食，表现出神经生理味觉反应的长期缺陷。令人惊讶的是，完整的味觉受体在对侧去神经后几天内也表现出味觉反应的改变。事实上，缺钠大鼠免疫活性的上调可导致完整 CT 神经恢复正常味觉反应。感觉和免疫功能之间的这种新的相互作用是出乎意料的，目前人们对免疫系统在正常或退化味觉系统中的作用知之甚少。去神经支配后味觉功能发生变化的部位是味觉受体细胞上的阿米洛利敏感钠通道（ENaC）。我们的长期目标是确定免疫系统调节 ENaC 功能的机制。在目前的提议中，必须首先鉴定出在退化过程中可能影响味觉功能的免疫细胞。将识别、计数白细胞亚型，并在切片后随时间绘制它们与去神经和完整味蕾的空间关系。粘附分子的表达是白细胞进入组织的重要信号，将在味觉受体细胞去神经支配后进行检查。还将研究由味觉受体细胞的单侧去神经支配引发的白细胞增殖和激活。我们假设，在对照喂养的大鼠中进行 CT 切片后，这些免疫活性测量值均上调，但限钠大鼠则没有上调。事实上，有证据表明饮食限制钠会抑制免疫。最后，特定的白细胞群将被耗尽，并通过神经生理学评估味觉系统退化的功能后果。白细胞耗竭后还将检查 ENaC 表达，以确定白细胞对通道的调节是否是味觉受体细胞中钠转导改变的机制。这些实验将为特定白细胞群对体内味觉功能的影响提供有力的证据。拟议的研究对于我们理解神经元、感觉受体细胞和白细胞之间的功能相互作用以及损伤后的神经可塑性也很重要。