Age-related structural and functional changes of the intracardiac nervous system.

Aging Heart rhythm Intracardiac nervous system aging Schwann cell

Journal

Journal of molecular and cellular cardiology
ISSN: 1095-8584
Titre abrégé: J Mol Cell Cardiol
Pays: England
ID NLM: 0262322

Informations de publication

Date de publication:
14 Dec 2023
Historique:
received: 14 08 2023
revised: 14 11 2023
accepted: 11 12 2023
medline: 17 12 2023
pubmed: 17 12 2023
entrez: 16 12 2023
Statut: aheadofprint

Résumé

Although aging is known to be associated with an increased incidence of both atrial and ventricular arrhythmias, there is limited knowledge about how Schwann cells (SC) and the intracardiac nervous system (iCNS) remodel with age. Here we investigate the differences in cardiac SC, parasympathetic nerve fibers, and muscarinic acetylcholine receptor M2 (M2R) expression in young and old mice. Additionally, we examine age-related changes in cardiac responses to sympathomimetic and parasympathomimetic drugs. Lower SC density, lower SC proliferation and fewer parasympathetic nerve fibers were observed in cardiac and, as a control sciatic nerves from old (20-24 months) compared to young mice (2-3 months). In old mice, CSPG4 was increased in sciatic but not cardiac nerves. Expression of M2R was lower in ventricular myocardium and ventricular conduction system from old mice compared to young mice, while no significant difference was seen in M2R expression in sino-atrial or atrio-ventricular node pacemaker tissue. Heart rate was slower and PQ intervals were longer in Langendorff-perfused hearts from old mice. Ventricular tachycardia and fibrillation were more frequently observed in response to carbachol administration in hearts from old mice versus those from young mice. On the background of reduced presence of SC and parasympathetic nerve fibers, and of lower M2R expression in ventricular cardiomyocytes and conduction system of aged hearts, the propensity of ventricular arrhythmogenesis upon parasympathomimetic drug application is increased. Whether this is caused by an increase in heterogeneity of iCNS structure and function remains to be elucidated.

Sections du résumé

BACKGROUND BACKGROUND
Although aging is known to be associated with an increased incidence of both atrial and ventricular arrhythmias, there is limited knowledge about how Schwann cells (SC) and the intracardiac nervous system (iCNS) remodel with age. Here we investigate the differences in cardiac SC, parasympathetic nerve fibers, and muscarinic acetylcholine receptor M2 (M2R) expression in young and old mice. Additionally, we examine age-related changes in cardiac responses to sympathomimetic and parasympathomimetic drugs.
METHODS AND RESULTS RESULTS
Lower SC density, lower SC proliferation and fewer parasympathetic nerve fibers were observed in cardiac and, as a control sciatic nerves from old (20-24 months) compared to young mice (2-3 months). In old mice, CSPG4 was increased in sciatic but not cardiac nerves. Expression of M2R was lower in ventricular myocardium and ventricular conduction system from old mice compared to young mice, while no significant difference was seen in M2R expression in sino-atrial or atrio-ventricular node pacemaker tissue. Heart rate was slower and PQ intervals were longer in Langendorff-perfused hearts from old mice. Ventricular tachycardia and fibrillation were more frequently observed in response to carbachol administration in hearts from old mice versus those from young mice.
CONCLUSIONS CONCLUSIONS
On the background of reduced presence of SC and parasympathetic nerve fibers, and of lower M2R expression in ventricular cardiomyocytes and conduction system of aged hearts, the propensity of ventricular arrhythmogenesis upon parasympathomimetic drug application is increased. Whether this is caused by an increase in heterogeneity of iCNS structure and function remains to be elucidated.

Identifiants

pubmed: 38103633
pii: S0022-2828(23)00196-7
doi: 10.1016/j.yjmcc.2023.12.002
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

Copyright © 2023. Published by Elsevier Ltd.

Déclaration de conflit d'intérêts

Declaration of Competing Interest None declared.

Auteurs

Eliza Sassu (E)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79110 Freiburg, Germany.

Gavin Tumlinson (G)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany; Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany.

Dragana Stefanovska (D)

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79110 Freiburg, Germany.

Marbely C Fernández (MC)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Pia Iaconianni (P)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Josef Madl (J)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Tomás Brennan (T)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Manuel Koch (M)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Breanne A Cameron (BA)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Sebastian Preissl (S)

Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79110 Freiburg, Germany.

Ursula Ravens (U)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany.

Franziska Schneider-Warme (F)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, and Faculty of Biology, University of Freiburg, Freiburg, Germany.

Peter Kohl (P)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany; CIBSS Centre for Integrative Biological Signalling Studies, and Faculty of Biology, University of Freiburg, Freiburg, Germany.

Callum M Zgierski-Johnston (CM)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany. Electronic address: callum.michael.johnston@uniklinik-freiburg.de.

Luis Hortells (L)

Institute for Experimental Cardiovascular Medicine, University Heart Center Freiburg Bad Krozingen, University of Freiburg, 79110 Freiburg, Germany; Faculty of Medicine, University of Freiburg, 79110 Freiburg, Germany; Institute of Experimental and Clinical Pharmacology and Toxicology, University of Freiburg, 79110 Freiburg, Germany. Electronic address: luis.hortells@pharmakol.uni-freiburg.de.

Classifications MeSH