Aging, Hypoxia, and Sympathetic Cardiac Projections

衰老、缺氧和交感心脏投射

• 批准号: 6727120
• 负责人: ZIXI Jack CHENG
• 金额: $ 7.33万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-01-01 至 2005-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6727120
• 关键词: aging; axon; chronic disease /disorder; confocal scanning microscopy; heart innervation; laboratory rat; myocardial ischemia /hypoxia; neuronal guidance; neuronal transport; sympathetic nervous system

Aging and the syndrome of obstructive sleep apnea, which is characterized by chronic intermittent hypoxia (CIH), are commonly associated with increased incidence and severity of cardiovascular diseases, including hypertension, reduced cardiac reflexes, orthostatic intolerance, cardiac failure, and sudden cardiac death. However, our understanding of the neural mechanisms underlying these dysfunctions is impeded by a lack of structural information on autonomic nerve terminals and the circuitry within the cardiac tissues. Sympathetic cardiac nerves originate from the stellate ganglion. The overall goal of the present application is to determine the sympathetic cardiac nerve innervation and remodeling induced by aging, CIH, or both. Sympathetic cardiac projections and reorganization will be measured in young, middle-age, and aged Fischer 344 rats. The sympathetic cardiac axons and terminals will be examined qualitatively and quantitatively using a battery of novel anatomical techniques that will include anterograde neural tracing, stereological counting, confocal microscopy, and Neurolucida 3-D digitization. Specific Aim 1: To determine the organization and reorganization of sympathetic efferent projection to the heart of young (3-4 months), middle-age (12-14 months), and aged (24-27 months) F344 rats. Specific Aim 2: To establish whether CIH will remodel sympathetic efferent axons and terminals in heart of young F344 rats, and whether aging and CIH will interact to induce even more severe sympathetic cardiac axonal remodeling than those produced by either aging or CIH alone. Collectively, the proposed experiments will advance our knowledge of brain-heart interactions and provide unique insights into the remodeling of sympathetic outflow to cardiac tissues during aging and following CIH.

衰老和以慢性间歇性缺氧（CIH）为特征的阻塞性睡眠呼吸暂停综合征通常与心血管疾病的发病率和严重程度增加有关，包括高血压、心脏反射减弱、直立不耐受、心力衰竭和心源性猝死。然而，由于缺乏自主神经末梢和心脏组织内回路的结构信息，我们对这些功能障碍背后的神经机制的理解受到阻碍。心脏交感神经起源于星状神经节。本申请的总体目标是确定由衰老、CIH或两者引起的交感心脏神经支配和重塑。将测量年轻、中年和老年 Fischer 344 大鼠的交感心脏投射和重组。将使用一系列新颖的解剖技术对交感心脏轴突和末梢进行定性和定量检查，其中包括 顺行神经追踪、体视计数、共焦显微镜和 Neurolucida 3-D 数字化。 具体目标 1：确定年轻（3-4 个月）、中年（12-14 个月）和老年（24-27 个月）F344 大鼠的交感神经传出投射到心脏的组织和重组。具体目标 2：确定 CIH 是否会重塑年轻 F344 大鼠心脏中的交感传出轴突和末梢，以及衰老和 CIH 是否会相互作用，诱导比衰老或单独 CIH 产生的更严重的交感心脏轴突重塑。总的来说，所提出的实验将增进我们对脑-心相互作用的了解，并为衰老和 CIH 后心脏组织交感神经流出的重塑提供独特的见解。