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）：味觉系统能够在对味道受体细胞的神经修饰后具有显着的可塑性。神经部分时的环境影响在这种功能可塑性中起着重要作用。成年大鼠在支配味觉受体细胞的丘巴尼（CT）神经切片后不久将其放置在钠限制性饮食中。令人惊讶的是，完整的味觉受体还表现出对侧神经支配后几天的味觉反应改变。实际上，缺乏钠的大鼠免疫活性的上调会导致完整CT神经中正常味觉反应的恢复。感觉和免疫功能之间的这种新型相互作用是出乎意料的，目前，免疫系统在正常或退化味觉系统中的作用知之甚少。去神经后，味觉功能变化的部位是味觉受体细胞上的艾米洛里胶敏感钠通道或ENAC。我们的长期目标是确定免疫系统调节ENAC功能的机制。在当前的建议中，必须首先确定潜在地影响退化期间味觉功能的免疫细胞。白细胞亚型将被鉴定，计数，并在截面后随时间映射的无效和完整的味蕾的空间关系。粘附分子的表达是白细胞进入组织的重要信号，将在对味觉受体细胞的神经膜上进行检查。还将研究白细胞增殖和通过单侧神经受体细胞神经化的激活。我们假设在对照喂养但不限制钠限制的大鼠CT切片后，这些免疫活性测量中的每一个都在上调。确实，有证据表明饮食钠限制是免疫抑制的。最后，将耗尽白细胞的特定种群，并在神经生理上评估退化的味觉系统的功能后果。白细胞耗竭后还将检查ENAC表达，以确定通道的白细胞调节是否是改变味觉受体细胞中钠转导的机制。这些实验将为特定白细胞种群对体内味觉功能的影响提供有力的证据。提出的研究对于我们对神经元，感觉受体细胞和白细胞之间的功能相互作用以及损伤后神经可塑性的功能相互作用也很重要。