Inhibition of axonal growth from sensory neurons by excess nerve growth factor

Anna M. Conti, Stephanie J. Fischer, Anthony John Windebank

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Abstract

Fifteen-day embryonic rat dorsal root ganglion (DRG) neurons were exposed to 1 to 200 ng/ml nerve growth factor (NGF). Maximal neurite outgrowth was obtained with 10 to 20 ng/ml. Neurite outgrowth was reduced to 89% of maximal by increasing NGF to 50 ng/ml, to 66% by 100 ng/ml, and to 18% by 200ng/ml NGF. Identical effects were seen with mouse 2.5S NGF and recombinant human NGF. Neuron cell counts demonstrated that significant cell death did not occur. In time course experiments, significant inhibition, compared with control, began within 1 hour of adding 200 ng/ml and 3 hours of adding 50 ng/ml NGF. The inhibitory effect of NGF on neurite outgrowth was reversed within 3 hours when DRG were incubated with 5 ng/ml NGF after treatment with 50 or 200 ng/ml NGF medium for 12 hours. The inhibition demonstrated for neurons did not occur in PC12 cells; axonal growth was not inhibited by up to 1,000 ng/ml NGF. Excess brain-derived neurotrophic factor or neutrophin-3 did not inhibit neurite outgrowth. We conclude that high concentrations of NGF produces specific and reversible arrest of neurite outgrowth from sensory neurons. This observation has important clinical implications, because these inhibitory concentrations have been exceeded when NGF has bee administered into the central nervous system of humans and animals.

Original languageEnglish (US)
Pages (from-to)838-846
Number of pages9
JournalAnnals of Neurology
Volume42
Issue number6
DOIs
StatePublished - Dec 1997

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Nerve Growth Factor
Sensory Receptor Cells
Growth
Spinal Ganglia
Neurons
Bees
PC12 Cells
Brain-Derived Neurotrophic Factor
Cell Death
Central Nervous System
Cell Count
Neuronal Outgrowth

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Inhibition of axonal growth from sensory neurons by excess nerve growth factor. / Conti, Anna M.; Fischer, Stephanie J.; Windebank, Anthony John.

In: Annals of Neurology, Vol. 42, No. 6, 12.1997, p. 838-846.

Research output: Contribution to journalArticle

Conti, Anna M. ; Fischer, Stephanie J. ; Windebank, Anthony John. / Inhibition of axonal growth from sensory neurons by excess nerve growth factor. In: Annals of Neurology. 1997 ; Vol. 42, No. 6. pp. 838-846.
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