Part and Parcel of the Cardiac Autonomic Nerve System: Unravelling Its Cellular Building Blocks during Development

Abstract

The autonomic nervous system (cANS) is essential for proper heart function, and complications such as heart failure, arrhythmias and even sudden cardiac death are associated with an altered cANS function. A changed innervation state may underlie (part of) the atrial and ventricular arrhythmias observed after myocardial infarction. In other cardiac diseases, such as congenital heart disease, autonomic dysfunction may be related to disease outcome. This is also the case after heart transplantation, when the heart is denervated. Interest in the origin of the autonomic nerve system has renewed since the role of autonomic function in disease progression was recognized, and some plasticity in autonomic regeneration is evident. As with many pathological processes, autonomic dysfunction based on pathological innervation may be a partial recapitulation of the early development of innervation. As such, insight into the development of cardiac innervation and an understanding of the cellular background contributing to cardiac innervation during different phases of development is required. This review describes the development of the cANS and focuses on the cellular contributions, either directly by delivering cells or indirectly by secretion of necessary factors or cell-derivatives.

Alterations in the autonomic nerve activities of prenatal autism model mice treated with valproic acid at different developmental stages

“…It has been suggested that neural crest cell (NCC) differentiation toward sympathetic and parasympathetic neurons depends on the expression of their neurotransmitters and the synthesis of enzymes and transcription factors 37 . Around E12.5, migrating NCCs play a role in the development of cardiac innervation and conduction 37 . Although VPA has multiple putative actions, including an increase in γ-aminobutyric acid (GABA) levels, a decrease in aspartate levels, and the blockade of sodium, calcium, and potassium voltage-gated channels, it has been suggested that histone deacetylase (HDAC) inhibition underlies the causal relationship between VPA and ASD 9,38 .…”

“…We speculate that the delay in sympathetic development became more apparent at E18.5 vs. E15.5. Genes such as BMP, MASH1, PHOX2B, GATA3 and HAND2 are important for NCC differentiation into sympathetic neurons 37 ; therefore, these genes would be involved in the changes in sympathetic activity caused by prenatal VPA administration. Thus, the prenatal administration of VPA changes the expression level of various molecules, which might have affected the development and/ or maturation of the autonomic nervous system.…”

Chronic Exposure to Low Concentration Lead Chloride-Induced Anxiety and Loss of Aggression and Memory in Zebrafish

“…Catecholamines are regulated by the activation of the adrenal medulla. Under stress, an increase in dopamine, norepinephrine, and epinephrine levels occurs [42]. Furthermore, the hormone cortisol has been known to increase as a response to stress [43,44].…”

In vitro generation of functional murine heart organoids via FGF4 and extracellular matrix

“…suggesting that Nestin-positive cells derived from NCCs may contribute to cardiac innervation and conduction through the cardiac autonomic nervous system 25,53 .…”