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.

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和衰老通常与心血管疾病的发病率和严重程度增加相关，包括高血压、心反射降低、直立耐受不良、心力衰竭和心源性猝死。然而，我们对这些功能障碍背后的神经机制的理解受到缺乏心脏组织内自主神经末梢和电路的结构信息的阻碍。心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或两者诱导的交感心神经神经支配和重塑。将在年轻、中年和老年Fischer 344大鼠中测量交感神经心脏投射和重组。交感神经的心脏轴突和终端将定性和定量检查使用一组新的解剖技术，将包括 顺行神经追踪、体视学计数、共聚焦显微镜和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大鼠心脏交感传出投射的组织和重组。具体目标二：研究CIH是否会重塑年轻F344大鼠心脏交感传出神经轴突和终末，以及衰老和CIH是否会相互作用，诱导比衰老或CIH单独产生的更严重的交感神经心脏轴突重塑。总的来说，拟议的实验将推进我们的知识，脑-心相互作用，并提供独特的见解重塑交感神经流出心脏组织在老化和CIH后。