Developmental changes in neurite outgrowth responses of dorsal root and sympathetic ganglia to GDNF, neurturin, and artemin

Abstract

The ability of glial cell line-derived neurotrophic factor (GDNF), neurturin, and artemin to induce neurite outgrowth from dorsal root, superior cervical, and lumbar sympathetic ganglia from mice at a variety of development stages between embryonic day (E) 11.5 and postnatal day (P) 7 was examined by explanting ganglia onto collagen gels and growing them in the presence of agarose beads impregnated with the different GDNF family ligands. Artemin, GDNF, and neurturin were all capable of influencing neurite outgrowth from dorsal root and sympathetic ganglia, but the responses of each neuron type to the different ligands varied during development. Neurites from dorsal root ganglia responded to artemin at P0 and P7, to GDNF at E15.5 and P0, and to neurturin at E15.5, P0, and P6/7; thus, artemin, GDNF, and neurturin are all capable of influencing neurite outgrowth from dorsal root ganglion neurons. Neurites from superior cervical sympathetic ganglia responded significantly to artemin at E15.5, to GDNF at E15.5 and P0, and to neurturin at E15.5. Neurites from lumbar sympathetic ganglia responded to artemin at all stages from E11.5 to P7, to GDNF at P0 and P7 and to neurturin at E11.5 to P6/7. Combined with the data from previous studies that have examined the expression of GDNF family members, our data suggest that artemin plays a role in inducing neurite outgrowth from young sympathetic neurons in the early stages of sympathetic axon pathfinding, whereas GDNF and neurturin are likely to be important at later stages of sympathetic neuron development in inducing axons to enter particular target tissues once they are in the vicinity or to induce branching within target tissues. Superior cervical and lumbar sympathetic ganglia showed temporal differences in their responsiveness to artemin, GDNF, and neurturin, which probably partly reflects the rostrocaudal development of sympathetic ganglia and the tissues they innervate.

Persistent restoration of sensory function by immediate or delayed systemic artemin after dorsal root injury

“…Artemin promoted growth ofNF200-, CGRP-or P2X 3 -labeled sensory fibers through the DREZ in a manner that was consistent with the level of expression of GFRα3 and RET found on these neurons after nerve injuries 37 . These findings suggest that limited regeneration (that is, approximately 50% of sensory fibers and synaptic potential amplitudes were approximately one-third of control values) is sufficient to restore behavioral responses to nociceptive stimuli, as well as to substantially improve sensorimotor function involving proprioception and touch.…”

“…Artemin acts through the GFRα3 receptor coupled to the RET signaling protein [34][35][36][37] , and DRC-induced changes in the expression of GFRα3 or RET in peripheral nerves may influence their regeneration. Notably, artemin treatment in sham-operated rats did not alter GFRα3 or RET expression in sensory neurons.…”

Glial Cell Line-Derived Neurotrophic Factor and Neurturin Inhibit Neurite Outgrowth and Activate RhoA through GFRα2b, an Alternatively Spliced Isoform of GFRα2

“…It is well documented that GDNF and NTN are potent trophic factors that have potent effects on neuronal differentiation and promote survival and sprouting of ventral mesencephalic dopaminergic neurons in primary cultures and other neuronal cultures (Lin et al, 1993;Akerud et al, 1999;Baloh et al, 2000;Yan et al, 2003;Wanigasekara and Keast, 2005;Zihlmann et al, 2005). The finding in this study of a particular alternatively spliced variant of GFR␣2 inhibiting neurite outgrowth was unexpected.…”

p75 reduces β-amyloid-induced sympathetic innervation deficits in an Alzheimer's disease mouse model

“…Thus, p75 is able to antagonize the detrimental effects of A␤ through promoting NGF signaling pathways. In addition to NGF, glial cell line-derived neurotrophic factor (GDNF) has been shown to promote neurite outgrowth from sympathetic neurons (32). Interestingly, GDNF signaling is mediated by a GPI-linked receptor GDNF receptor-␣1.…”