Gastrointestinal Tract Innervation: Patterns of Aging

描述(申请人提供)：胃肠道疾病常见于 老年人。过去十年的研究已经证实，这些 与年龄相关的疾病与脑内神经元的显著损失有关 胃肠道壁上的自主神经丛或肠道神经丛。 然而，最初的形态观察主要集中在 从而确定细胞丢失的发生。上提供的信息很少 损失的空间模式(例如，大肠受影响更大 比小肠)，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 丢失的特异性(例如，哪些形态和神经化学成分 表型死亡)。此外，衰老研究在很大程度上忽略了粘膜下 胃部和肠部的神经丛。此外，这样的研究并没有 检查与年龄相关的外在运动和感觉神经的变化 把肠道和中枢神经系统联系起来。目前的建议是长期的 目标，统一了它的五个具体目标，是为了描述 肠道神经元老化的空间、时间和表型模式 免疫组织化学和顺行追踪方案。目标1：意志 确定随年龄增长的肌间神经细胞丢失是否特定于 特殊的神经化学表型。目标2：将检查空间和时间 粘膜下神经丛中与年龄相关的形态变化模式。目标3： 将探索肠道失去外源性迷走神经输入是否会沉淀 或者，反之，这种外源性神经支配是否 负责部分地区小区丢失的预防工作。目标4：意志 研究交感神经老化的时空变化模式 神经系统运动和内脏向胃肠道的传入投射 一条小路。目标5：将评估与年龄相关的外源性神经元重构 整个胃肠道的末梢。项目的总体目标是更好地 了解生物多样性的空间、时间和表型变化模式。 老化的胃肠道的神经支配。此信息将 提供干预或合理策略所需的基础 一些动态平衡和消化系统紊乱的临床处理 影响食欲、摄取、消化和运动，并最终 营养与健康，在老年人身上。

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.