Nerve growth factor collaborates with myocyte‐derived factors to promote development of presynaptic sites in cultured sympathetic neurons

Abstract

Nerve growth factor (NGF) acutely modulates synaptic transmission between sympathetic neurons and their cardiac myocyte targets. NGF also has developmental effects in establishing the level of synaptic transmission between sympathetic neurons and myocytes in culture, although little is known about the mechanisms by which NGF influences this synaptic connectivity. Here we report that NGF acts in conjunction with factors produced by cardiac myocytes to promote neuronal contact with the target and the extension of synaptic vesicle‐containing growth cones. In conjunction with previously published results showing that NGF has long‐term effects on synaptic transmission between sympathetic neurons and myocytes, this work suggests that NGF acts to promote sympathetic neurotransmission by increasing the number of sympathetic fibers establishing target contact. Further, we found that developmental changes in cardiac myocytes led to an increase in the density of synaptic vesicle–containing variocosities along sympathetic fibers, a process regulated by NGF. Thus, as myocytes mature they produce factors that promote the formation of sympathetic presynaptic structures. These results argue that multiple target interactions regulate the extent of synapse formation between sympathetic neurons and cardiac cells and suggest that NGF promotes presynaptic development by increasing neuronal contact with myocyte‐derived cell surface or matrix‐associated factors. © 2000 John Wiley & Sons, Inc. J Neurobiol 43: 460–476, 2000

Sympathetic neurons are a powerful driver of myocyte function in cardiovascular disease

“…It is clear that both the vascular bed and the heart of SHRs have significantly higher expression of nerve growth factor (NGF)37. As such, it is conceivable that increased NGF expression could result in increased innervation2538 in the SHR animals, since hyper-innervation has been demonstrated in the stroke-prone SHRs both prior to, and after the development of hypertension39. This was postulated to be caused by hyperactivity of the stellate ganglion and could help explain the increased incidence of arrhythmias associated with hypertension4041.…”

Back and forth in time: Directing age in iPSC-derived lineages

“…For example, target-derived neurotrophic and axonal guidance factors are crucial in controlling neuronal survival, synaptic connectivity, synapse formation and functional maturation 56 . The interaction of motoneurons with skeletal muscle 57 or cardiomyocyte innervation by sympathetic neurons 58 represent classic model systems to study non-cell autonomous factors affecting neuronal maturation. Establishing co-culture paradigms that implement target cell types may prove particularly beneficial for establishing PSC-derived, disease-relevant, functional assays to study skeletal muscle and cardiac fuction 59,60 .…”

Autonomic cardiac innervation

“…Sympathetic neurons in the first postnatal week compete for target-derived NGF, as NGF levels in the immediate postnatal period, despite fluctuations, are still subsaturating, with apoptosis occurring for those neurons unable to obtain sufficient levels of NGF 161 - 166 . In addition to neuronal survival, NGF also enhances synaptic strength between sympathetic neurons and neonatal cardiomyocytes by promoting the formation of terminal varicosities 167 , 168 . Intriguingly, NGF may also modulate β3-adrenergic receptor expression by cardiomyocytes, a finding with possible ramifications for arrhythmia generation 169 as β3-adenoceptor expression is increased in some cardiac pathological states.…”