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.

年龄增长和以慢性间歇性低氧(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生率和严重性增加有关，包括高血压、心脏反射减退、立位耐受不良、心力衰竭和心源性猝死。然而，由于缺乏关于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的神经机制的理解受到阻碍。交感神经起源于星状神经节。本应用的总体目标是确定交感神经的神经支配和由老化、脑出血或两者兼而有之引起的重塑。交感神经心脏投射和重组将在年轻、中年和老年费舍尔344大鼠中进行测量。交感心脏轴突和终末将使用一系列新的解剖学技术进行定性和定量检查，这些技术包括 顺行神经追踪、体视学计数、共聚焦显微镜和神经荧光素三维数字化。 具体目的1：研究青年(3-4月龄)、中年(12-14月龄)和老年(24-27月龄)F344大鼠心脏交感神经传出投射的组织和重组。具体目的2：确定脑出血是否会重塑幼年F344大鼠心脏交感传出轴突和终末，以及增龄和脑出血是否会相互作用，导致交感神经轴突重塑甚至比单纯脑出血或老年大鼠更严重。总之，拟议的实验将促进我们对脑心相互作用的了解，并为交感神经流出到心脏组织的交感神经在衰老和脑出血后的重塑提供独特的见解。