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

Peter Wiklund, Per Ekström

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

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. (C) 2000 John Wiley and Sons, Inc.

Original languageEnglish
Pages (from-to)142-151
Number of pages10
JournalJournal of Neurobiology
Volume45
Issue number3
DOIs
Publication statusPublished - 2000 Nov 15

Subject classification (UKÄ)

  • Cell Biology

Keywords

  • BDNF
  • Brain-derived neurotrophic factor
  • Regeneration
  • Sensory neurons
  • Vagus

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