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.

Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia

“…The myocyte response to neuronal stimulation is greater in 50 ng/ml NGF than in 5 ng/ml NGF and the connection probability is increased. No difference in basic electrophysiological features such as the resting membrane potential is observed but the proportion of myocytes with dense neuritic contacts varies with NGF (Lockhart et al 2000). The number of SV2-containing neurite endings is increased at higher NGF concentrations and by interaction with mature myocytes.…”

Target-Dependent Release of a Presynaptic Neuropeptide Regulates the Formation and Maturation of Specific Synapses inAplysia

“…Thus, sensorin, like neurotrophins such as BDNF, can have multiple functions, including producing neurotransmitter-like responses in some follower cells and acting as a neuromodulator in producing longterm facilitation when it interacts with autoreceptors whose signaling pathway is also activated by the stimuli required to produce long-term facilitation (Hu et al, 2004). Neurotrophins and their receptors are one group of factors that contribute not only to proliferation, survival, and early differentiation of neurons but also to the formation and maintenance of peripheral synapses (Schafer et al, 1983;Gonzalez et al, 1999;Wells et al, 1999;Lockhart et al, 2000;Belluardo et al, 2001;Chen et al, 2002) and the formation, fine-tuning, maintenance, and longterm modulation of central synapses (Cabelli et al, 1995(Cabelli et al, , 1997Kang and Schuman, 1995;McAllister et al, 1997;Martinez et al, 1998;Cohen-Cory, 2002;Vicario-Abejon et al, 2002).…”

Sitagliptin decreases ventricular arrhythmias by attenuated glucose-dependent insulinotropic polypeptide (GIP)-dependent resistin signalling in infarcted rats

“…Nerve growth factor (NGF) belongs to the neurotrophin family of proteins, which play an essential role in the differentiation, survival and synaptic activity of peripheral sympathetic and sensory nervous systems [13]. A number of cell types have been shown to secrete NGF, including fibroblasts [14], cardiac myocytes [15] and vascular endothelial cells [16].…”