Axonal outgrowth from adult mouse nodose ganglia in vitro is stimulated by neurotrophin-4 in a Trk receptor and mitogen-activated protein kinase-dependent way.
The actions of neurotrophic factors on sensory neurons of the adult nodose ganglion were studied in vitro. The ganglia were explanted in an extracellular matrix-based gel that permitted observation of the growing axons. Neurotrophin-4 (NT-4) was a very efficient stimulator of outgrowth of axons from the nodose ganglion and had almost doubled the outgrowth length when this was analyzed after 2 days in culture. Brain-derived neurotrophic factor also stimulated outgrowth, but to a lesser degree, whereas NT-3 gave only weak stimulatory tendencies. Nerve growth factor and glial cell line-derived neurotrophic factor both lacked stimulatory effects. NT-4 is known to act via TrkB receptors, and the presence of these on growing nodose neurons was demonstrated immunohistochemically. In line with a Trk-mediated growth effect, the NT-4 stimulation was abolished by K252a, a selective inhibitor of neurotrophin receptor-associated tyrosine kinase activity. K252a had no effect on the unstimulated preparation. NT-4 treatment led to activation of the mitogen-activated protein kinase and inhibition of the latter pathway by PD98059 significantly reduced the NT-4 stimulated outgrowth, whereas the drug had no effect on the unstimulated growth. In conclusion, the data suggest that NT-4 can serve as a powerful growth factor for neurons of adult nodose ganglia and that the growth stimulation involves TrkB- and mitogen-activated protein kinase.
Wiklund
P
P
Department of Animal Physiology, University of Lund, Helgonavägen 3B, SE-223 62 Lund, Sweden.
Ekström
P A
PA
D000818:Animals; D001369:Axons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism; D005260:Female; D008297:Male; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D020932:Nerve Growth Factor / Q000494:pharmacology; D009414:Nerve Growth Factors / Q000378:metabolism / Q000494:pharmacology*; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D009475:Neurons, Afferent / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D020933:Neurotrophin 3 / Q000494:pharmacology; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000254:growth & development; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020932:Nerve Growth Factor; D020794:Receptor Protein-Tyrosine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D020928:Mitogen-Activated Protein Kinases; C073922:neurotrophin 4