Degenerative Changes in the Taste System

描述(申请人提供)：味觉系统能够在味觉感受器细胞失神经后具有显著的可塑性。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)神经后不久就被置于限钠饮食中，表现出神经生理学味觉反应的长期缺陷。令人惊讶的是，在对侧失去神经后的几天内，完整的味觉感受器也表现出改变的味觉反应。事实上，缺钠大鼠的免疫活性上调会导致完整的CT神经恢复正常的味觉反应。这种感觉和免疫功能之间的这种新颖的相互作用是意想不到的，目前人们对免疫系统在正常或退化的味觉系统中的作用知之甚少。失神经后味觉功能改变的部位是味觉感受器细胞上的阿米洛利敏感钠通道或ENaC。我们的长期目标是确定免疫系统调节ENaC功能的机制。在目前的提案中，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。在切片后，将识别、计数白细胞亚型，并绘制其与失神经和完整味蕾的空间关系图。黏附分子的表达是白细胞进入组织的基本信号，将在味觉感受器细胞失神经后进行检测。此外，还将研究味觉感受器细胞单侧失神经所引发的白细胞增殖和激活。我们假设，在对照饲养但没有钠限制的大鼠的CT切片后，这些免疫活性的每一项指标都被上调。事实上，有证据表明，限制饮食中的钠是免疫抑制的。最后，特定群体的白细胞将被耗尽，并对退化的味觉系统的功能后果进行神经生理学评估。在白细胞耗尽后，还将检测ENAC的表达，以确定白细胞对该通道的调节是否是味觉感受器细胞钠转导改变的机制。这些实验将为体内特定白细胞群对味觉功能的影响提供强有力的证据。拟议的研究对于我们理解神经元、感觉感受器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。

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.