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

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 org...

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Bibliographic Details
Published in:Amyotrophic lateral sclerosis and other motor neuron disorders 2001-06, Vol.2 (2), p.83-91
Main Author: M Bilak, Andrea M Corse, Ralph W Kuncl, Masako
Format: Article
Language:English
Subjects:
Als Glutamate Neurotrophic Factors Spinal Cord Synergy
Amyotrophic Lateral Sclerosis - drug therapy
Amyotrophic Lateral Sclerosis - physiopathology
Animals
Choline O-Acetyltransferase - metabolism
Culture Techniques
Disease Models, Animal
Glial Cell Line-Derived Neurotrophic Factor
Immunohistochemistry
Insulin-Like Growth Factor I - pharmacology
Insulin-Like Growth Factor I - therapeutic use
Motor Neurons - chemistry
Motor Neurons - drug effects
Motor Neurons - metabolism
Nerve Growth Factors
Nerve Tissue Proteins - pharmacology
Nerve Tissue Proteins - therapeutic use
Neurites - metabolism
Rats
Spinal Cord - cytology
Spinal Cord - physiology
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Summary: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.
ISSN:1466-0822
DOI:10.1080/146608201316949523