Degenerative Changes in the Taste System

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具有显著的可塑性。在神经节的时间环境的影响发挥了重要作用，在这种功能的可塑性。成年大鼠置于钠限制饮食切片后不久鼓索（CT）神经，支配味觉感受器细胞，表现出长期的赤字在神经生理味觉反应。令人惊讶的是，完整的味觉感受器在对侧去神经支配后的几天内也表现出改变的味觉反应。事实上，钠缺乏大鼠的免疫活性上调导致完整CT神经的正常味觉反应恢复。感觉和免疫功能之间的这种新的相互作用是出乎意料的，目前对免疫系统在正常或退化的味觉系统中的作用知之甚少。失神经后味觉功能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，必须首先确定在退化过程中可能影响味觉功能的免疫细胞。将鉴定、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必要信号，将在味觉受体细胞去神经后进行检查。白细胞的增殖和激活发起的味觉受体细胞的单侧去神经也将进行研究。我们假设，这些措施的免疫活性上调后CT切片控制喂养，但不限钠大鼠。事实上，有证据表明，饮食钠限制是免疫抑制。最后，白细胞的特定群体将被耗尽，并且神经生理学评估退化味觉系统的功能后果。还将在白细胞去除后检查ENaC表达，以确定通道的白细胞调节是否是味觉受体细胞中改变的钠转导的机制。这些实验将为特定白细胞群体对味觉功能的影响提供有力的证据。提出的研究也是重要的，我们了解神经元，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。

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.