Aging is associated with cardiac autonomic nerve fiber depletion and reduced cardiac and circulating BDNF levels
Andrea Elia1
Alessandro Cannavo2
Giuseppina Gambino2
Maria Cimini3
Nicola Ferrara1
Raj Kishore3
Nazareno Paolocci4
Giuseppe Rengo1
1.Department of Translational Medical Sciences,Federico Ⅱ University of Naples Italy;Istituti Clinici Scientifici ICS-Maugeri,Telese Terme (BN),Italy2.Department of Translational Medical Sciences,Federico Ⅱ University of Naples Italy3.Center for Translational Medicine,Department of Pharmacology,Lewis Katz School of Medicine,Temple University,Philadelphia,Pennsylvania,USA4.Division of Cardiology,Johns Hopkins University Medical Institutions,Baltimore,MD,USA;Department of Biomedical Sciences,University of Padova,Italy
摘要：Background Aging is a multifactorial process associated with an impairment of autonomic nervous system (ANS) function.Pro-gressive ANS remodeling includes upregulation of expression of circulating catecholamines and depletion of cardiac autonomic nerve fibers,and it is responsible,in part,for the increased susceptibility to cardiac diseases observed in elderly subjects.Neuro-trophic factors,such as brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF),are involved in synaptogenesis and neurite outgrowth processes,supporting neuronal cell differentiation and maturation.However,whether and how these factors and their downstream signaling are involved in cardiac aging remains unclear.Here,we tested whether,in the aged heart,the overall extent of autonomic fibers is reduced,owing to lower production of trophic factors such as BDNF and NGF.Methods In vivo,we used young (age:3 months;n-10) and old (age:24 months;n =11) male Fisher rats,whereas,we used human neuroblastoma (SH-SY5Y) cells in vitro.Results Compared to the young rats,old rats displayed a marked reduction in the overall ANS fiber density,affecting both sympathetic and cholinergic compartments,as indicated by dopamine β-hydroxylase (dβh) and vesicular acetylcholine transporter(VaChT) immunohistochemical staining.In addition,a marked downregulation of GAP-43 and BDNF protein was observed in the left ventricular lysates of old rats compared to those of young rats.Interestingly,we did not find any significant difference in cardiac NGF levels between the young and old groups.To further explore the impact of aging on ANS fibers,we treated SH-SYSY cells in vitro with serum obtained from young and old rats.Sera from both groups induced a remarkable increase in neuronal sprouting,as evidenced by a crystal violet assay.However,this effect was blunted in cells cultured with old rat serum and was accompanied by a marked reduction in GAP-43 and BDNF protein levels.Conclusions Our data indicate that physiological aging is associated with an impairment of ANS structure and function and that reduced BDNF levels are responsible,at least in part,for these phenomena.
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论文发表日期：2021-07-28
在线出版日期：2025-08-15（本平台首次上网日期，不代表文献的发表时间）
页数：11( 549-559 )