NEUROBIOLOGY OF VERTEBRATE OLFACTORY MUCOSA

本部分计划项目由两部分组成： 临床研究和基础科学研究。 的具体目标 临床研究的目的是确定吸入可卡因对 含有化学感受器的人鼻粘膜 嗅觉系统。 基础科学的具体目标 研究的目的是检验微绒毛细胞，或 “刷状细胞”，在人类的呼吸道中发现 有些哺乳动物是化学感受器 滥用可卡因是一种 迅速增长的流行病程度的重大健康问题。 尽管收集了大量关于可卡因滥用的数据， 我们的知识存在重大差距： 可卡因滥用对人鼻腔组织病理学的影响 粘膜及其独特的嗅觉受体神经元群体？ 嗅粘膜含有数百万个嗅觉感受器 神经元，每一个都是初级感觉细胞--双极神经元， 它的细胞体位于嗅上皮， 树突进入鼻腔和轴突的嗅球 大脑 这些"裸露的神经元"位于神经元的最前沿， 中枢神经系统，是人体内唯一的神经细胞 与环境直接接触的生物。 因此，委员会认为， 他们会直接接触吸入的可卡因 嗅 粘膜，不像其他神经组织，可以安全地活组织检查下， 局部麻醉，并通过电子显微镜检查，并将 拆除后再生。 因此，本项目将调查 可卡因滥用对人嗅觉影响组织病理学研究 受体，这将作为一个主要的模型系统， 可卡因及其混伪品对大鼠肝细胞超微结构的影响 人类中枢神经系统的组成部分。 嗅 人类和许多哺乳动物的上皮含有纤毛双极 嗅神经元和微绒毛细胞。 最近的证据 表明微绒毛细胞是感觉神经元。 因此，委员会认为， 似乎人类的嗅觉粘膜含有两个 嗅觉感受器细胞的形态学上不同的类别。 当 电镜观察，微绒毛细胞在细胞膜上的分布， 嗅粘膜显示出显著的超微结构 与气管中的"刷状细胞"相似， 细支气管，甚至是人类，老鼠， 和其他哺乳动物物种。 利用示踪技术 研究，计算机生成的三维重建 高压电子显微镜和免疫细胞化学， 该项目将测试的假设，刷细胞发现 在整个呼吸系统中，它们在本质上是化学感受性的。

This portion of the Program Project consists of two components: clinical studies and basic science studies. The specific aim of the clinical studies is to determine the effects of inhaled cocaine on the human nasal mucosa that contains the chemosensory receptors of the olfactory system. The specific aim of the basic science studies is to test the hypothesis that the microvillar cells, or "brush cells", found throughout the respiratory tract of humans and some mammals are chemoreceptors. Cocaine abuse is a rapidly-growing major health problem of epidemic proportions. Despite the wealth of data gathered on cocaine abuse, a significant gap in our knowledge exists: what are the histopathological effects of cocaine abuse on the human nasal mucosa and its unique population of olfactory receptor neurons? The olfactory mucosa contains several million olfactory receptor neurons, each of which is a primary sense cell--a bipolar neuron, whose cell body sits in the olfactory epithelium, that sends a dendrite into the nasal cavity and an axon to the olfactory bulb of the brain. These "naked neurons" sit right at the frontier of the central nervous system, and are the only nerve cells in the body that make direct contact with the environment. Consequently, they make direct contact with inhaled cocaine. The olfactory mucosa, unlike other nervous tissue, can be safely biopsied under local anesthesia and examined by electron microscopy, and will regenerate after removal. Therefore, this project will investigate the histopathology of cocaine abuse upon human olfactory receptors, which will serve as a major model system for the effects of cocaine and its adulterants upon the ultrastructure of components of the human central nervous system. The olfactory epithelium of humans and many mammals contains ciliated bipolar olfactory neurons and microvillar cells. Recent evidence indicates the microvillar cells are sensory neurons. Consequently, it seems that the human olfactory mucosa contains two morphologically distinct classes of olfactory receptor cell. When viewed by electron microscopy, the microvillar cells in the olfactory mucosa demonstrate a striking ultrastructural resemblance to the "brush cells" that are found in the trachea, bronchioles, and even alveoli deep in the lungs of humans, rats, and other mammalian species. Using the techniques of tracer studies, computer-generated three-dimensional reconstruction by high voltage electron microscopy, and immunocytochemistry, this project will test the hypothesis that the brush cells found throughout the respiratory system are chemoreceptive in nature.