Aging, Hypoxia, and Sympathetic Cardiac Projections

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、心脏反射降低、直立性不耐受、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电路的结构信息，我们对这些功能障碍背后的神经机制的理解受到阻碍。心交感神经起源于星状神经节。本应用的总体目标是确定由衰老、CIH或两者引起的交感神经支配和重构。将测量年轻、中年和老年Fischer 344大鼠的交感心脏投射和重组。交感心脏轴突和终末将定性和定量地检查使用一系列新的解剖技术，将包括

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.