Abstract 10272: Aging is Associated With Impaired Cardiac Autonomic Nervous System and Brain-derived Neurothrophic Factor (bdnf) Production

Introduction:Several studies have shown that aging is associated with alteration in the autonomic nervous system (ANS). In particular, aging is characterized by increased circulating catecholamines and lost of cardiac adrenergic fibers, which could explain the increased susceptibility of old subjects to cardiac diseases. Neurothrophic factors (NF) have an important role in modulating neuronal function and appear to be dysregulated in cardiac disorders. Whether and how these factors and their downstream signaling are involved in cardiac aging remains still unclear.Hypothesis:In vivo, young (age: 3 months; n=10) and old (age: 24 months; n=11) Fisher rats were used. In vitro,we used neuroblastoma human cells (SHSY-5Y).Results:Echocardiographic analysis did not show any significant difference in cardiac function (% fractional shortening) and remodeling (Left Ventricular [LV] internal diameters) between young and old rats. By hemodynamic, we observed a significant decrease in inotropic reserve after stimulation with isoproterenol in old compared to young rats. Old rats presented a significant reduction of cardiac ANS fibers density, both sympathetic (dopamine ?-hydroxylase, d?h) and cholinergic (vesicular acetylcholine transporter, VaChT) compared to young group, as assessed by immunofluorescence. Moreover, immunoblot analysis performed in LV lysates, demonstrated a significant downregulation of GAP-43 and brain derived neurothrophic factor (BDNF) levels in old rats compared to young ones. To further study the impact of aging on cardiac ANS, we stimulated SHSY-5Y cells in vitrowith either young or old rat blood serum. Both stimuli resulted in a significant increase in neuronal sprouting, assessed by crystal violet assay. However, neuronal function resulted significant blunted in presence of old rat serum. Finally, in cells treated with old rat serum we found a significant reduction in GAP- 43 levels compared to those treated with young rat serum.Conclusions:our data suggest that aging impairs neuronal function and NF signaling pathway, thus leading to altered homeostasis of cardiac ANS.