Gastrointestinal Tract Innervation: Patterns of Aging

描述（由申请人提供）：胃肠道疾病常见于 老年人。过去十年的研究表明， 与年龄有关的疾病与大脑中神经元的急剧损失有关。 在消化道壁中发现的自主神经丛或肠神经丛。 然而，最初的形态学观察主要集中在 从而确定发生了单元损失。关于这方面的资料很少。 损失的空间模式（例如，大肠受影响的程度 而不是小肠），溶解的时间模式（例如， 细胞死亡何时开始以及如何进展），或表型 损失的特异性（例如，形态学和神经化学 表型死亡）。此外，衰老研究在很大程度上忽视了粘膜下层 胃和肠中的神经丛。此外，这种研究并没有 检查了与年龄相关的外在运动和感觉神经支配的变化 连接肠道和中枢神经系统目前的建议是长期的 目标，统一其五个具体目标，是描述 肠道神经元老化的空间、时间和表型模式， 免疫组化和顺行束追踪方案。目标1：意愿 确定肌间神经元随年龄的损失是否是特定的， 特殊的神经化学表型目标2：将研究空间和时间 粘膜下神经丛中与年龄相关的形态学变化模式。目标3： 将探讨是否损失外部迷走神经输入到肠道沉淀 肠细胞损失，或者相反，这种外源性神经支配是否 负责防止某些区域中的小区丢失。目标4：意愿 研究老年交感神经系统变化的空间和时间模式 神经系统运动和内脏传入投射到胃肠 道。目的5：评估年龄相关的外源性神经元重塑 在整个胃肠道的末端。该项目的总体目标是更好地 了解空间，时间和表型变化的模式， 衰老胃肠道的神经支配。这些信息将 为合理的干预战略提供必要的基础，或 临床管理的一些稳态和消化系统疾病， 影响食欲、摄食、消化和运动， 老年人的营养和健康。

DESCRIPTION (provided by applicant): Gastrointestinal disorders are common in elderly individuals. Research in the last decade has established that these age-related disorders are correlated with dramatic losses of neurons in the autonomic, or enteric, plexuses found in the wall of the digestive tract. Initial morphological observations have, however, focused primarily on establishing that the cell losses occur. Little information is available on the spatial patterning of the losses (e.g., is the large intestine affected more than the small intestine), the temporal patterning of the dissolution (e.g., when does cell death start and how does it progress), or the phenotypic specificity of the losses (e.g., which morphological and neurochemical phenotypes die). In addition, aging research has largely ignored the submucosal plexus in the stomach and intestines. Furthermore, such research has not examined age-related alterations in the extrinsic motor and sensory innervation linking the gut to the central nervous system. The present proposal's long term objective, which unifies its five specific aims, is to characterize the spatial, temporal and phenotypic patterns of neuronal aging in the gut, using immunohistochemical and anterograde tract tracing protocols. Aim 1: will determine whether the myenteric neuronal losses with aging are specific to particular neurochemical phenotypes. Aim 2: will examine spatial and temporal patterns of age-related morphological changes in the submucosal plexus. Aim 3: will explore whether loss of extrinsic vagal inputs to the gut precipitates enteric cell losses or, conversely, whether such extrinsic innervation is responsible for the prevention of cell losses in some regions. Aim 4: will examine the spatial and temporal patterns of change in the aging sympathetic nervous system motor and visceral afferent projections to the gastrointestinal tract. Aim 5: will assess age-associated remodeling of extrinsic neuronal endings throughout the GI tract. The overall goal of the project is to better understand the patterns of spatial, temporal and phenotypic changes in the neural innervation of the aging gastrointestinal tract. This information will provide a foundation needed for rational strategies for interventions or clinical management of some of the homeostatic and digestive disorders that affect appetite, ingestion, digestion, and motility, as well as ultimately nutrition and health, in the elderly.