Aging, Hypoxia, and Sympathetic Cardiac Projections

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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.