Additivity and potentiation of IGF-I and GDNF in the complete rescue of postnatal motor neurons

M. M. Bilak, A. M. Corse, R. W. Kuncl

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Both growth and survival of motor neurons may depend on multiple neurotrophic factors. Individually, insulin-like growth factor I (IGF-I) and glial cell line-derived neurotrophic factor (GDNF) are potent neurotrophic/survival factors for postnatal motor neurons. Methods: We used an organotypic spinal cord model of glutamatergic degeneration in ALS to investigate whether IGF-I and GDNF interact to enhance motor neuron survival, their trophic effect on choline acetyltransferase (ChAT) activity, and their effect on neurite outgrowth. Results: We show that the combination of IGF-I and GDNF at active doses (1) is additively neuroprotective, (2) completely rescues rat motor neurons from chronic glutamate-mediated toxicity, and (3) additively upregulates motor neuron ChAT activity. Further, IGF-I, which by itself does not promote neurite outgrowth in this model, potentiates the neurite promoting action of GDNF. Conclusion: The results predict that IGF-I combined with GDNF may provide a better therapy for the treatment of motor neuron disorders such as amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy.

Original languageEnglish (US)
Pages (from-to)83-91
Number of pages9
JournalAmyotrophic Lateral Sclerosis and Other Motor Neuron Disorders
Volume2
Issue number2
DOIs
StatePublished - Oct 9 2001

Keywords

  • ALS
  • Glutamate
  • Neurotrophic factors
  • Spinal cord
  • Synergy

ASJC Scopus subject areas

  • Clinical Neurology

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