Neurotrophin-3 promotes the cholinergic differentiation of sympathetic neurons

Abstract

Neurotrophins influence the epigenetic shaping of the vertebrate nervous system by regulating neuronal numbers during development and synaptic plasticity. Here we attempt to determine whether these growth factors can also regulate neurotransmitter plasticity. As a model system we used the selection between noradrenergic and cholinergic neurotransmission by paravertebral sympathetic neurons. Developing sympathetic neurons express the neurotrophin receptors TrkA and TrkC, two highly related receptor tyrosine kinases. Whereas the TrkA ligand nerve growth factor (NGF) has long been known to regulate both the survival and the expression of noradrenergic traits in sympathetic neurons, the role of TrkC and of its ligand neurotrophin-3 (NT3) has remained unclear. We found that TrkC expression in the avian sympathetic chain overlaps substantially with that of choline acetyltransferase. In sympathetic chain explants, transcripts of the cholinergic marker genes choline acetyltransferase and vasoactive intestinal polypeptide were strongly enriched in the presence of NT3 compared with NGF, whereas the noradrenergic markers tyrosine hydroxylase and norepinephrine transporter were reduced. The transcription factor chicken achaete scute homolog 1 was coexpressed with cholinergic markers. The effects of NT3 are reversed and antagonized by NGF. They are independent of neuronal survival and developmentally regulated. These results suggest a role for NT3 as a differentiation factor for cholinergic neurons and establish a link between neurotrophins and neurotransmitter plasticity.

Neurotrophins: key regulators of cell fate and cell shape in the vertebrate nervous system

“…This leaves the prenatal role of the NT3/TrkC signaling system open in prenatal sympathetic neurons. Recent results obtained with avian neurons indicate that the NT3/TrkC system promotes the cholinergic differentiation of sympathetic neurons (Brodski et al 2000). This result is especially intriguing, as the same neurons seem to express both TrkA and TrkC (Brodski et al 2000).…”

“…Recent results obtained with avian neurons indicate that the NT3/TrkC system promotes the cholinergic differentiation of sympathetic neurons (Brodski et al 2000). This result is especially intriguing, as the same neurons seem to express both TrkA and TrkC (Brodski et al 2000). Yet the activation of TrkA by NGF promotes adrenergic differentiation, suggesting that signaling downstream of TrkA and TrkC can lead to surprisingly different outcomes in the same cells.…”

Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary

“…The inverse relationship between intraovarian NGF and VIP throughout the estrous cycle and the fact that NGF blocks the expression of VIP mRNA in many tissues (Zigmond & Sun 1997, Brodski et al 2000, Helke & Verdier-Pinard 2000 suggest that locally produced VIP may be in turn regulated by neural-derived NGF. If the intraovarian VIPergic system becomes active between DII and PE, when follicular selection and dominance is achieved, it is suggestive of functional complementarities between peptidergic input and noradrenergic innervation similar to that demonstrated previously for activation of NE system between PE and E (Ferruz et al 1991).…”

NT-3 attenuates the growth of human neuron cells through the ERK pathway

“…Neurotrophin 3 (NT-3) is indispensible for the development of muscle and tendon receptors (Brahimi et al 2014). The relationship between NT-3 and the functional efficiency of proprioceptive systems has been demonstrated using NT-3 knockout mice which do not develop proper proprioceptive innervation and die shortly after birth (Tafreshi et al 1998;Brodski et al 2000). NT-3 shows its function via its receptor (TrkC) (Brahimi et al 2014).…”