GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice

Glial cell line-derived neurotrophic factor (GDNF), a member of the TG F-beta superfamily, has been shown to be a highly potent neurotrophic factor that enhances survival of various neuronal cell types including motoneurons. To assess its therapeutic potential in treating neurodegenerative diseases...

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Bibliographic Details
Published in:The Journal of neuroscience 1996-04, Vol.16 (7), p.2335-2341
Main Authors: Sagot, Y, Tan, SA, Hammang, JP, Aebischer, P, Kato, AC
Format: Article
Language:English
Subjects:
Animals
Antibody Specificity
Axons - physiology
Capsules
Cell Death - drug effects
Cells, Cultured - cytology
Cells, Cultured - drug effects
Cricetinae
Drug Delivery Systems
Glial Cell Line-Derived Neurotrophic Factor
Kidney - cytology
Mice
Mice, Neurologic Mutants
Motor Neurons - cytology
Motor Neurons - drug effects
Myelin Sheath - drug effects
Nerve Degeneration - drug effects
Nerve Growth Factors - pharmacology
Nerve Tissue Proteins - immunology
Nerve Tissue Proteins - pharmacology
Rats
Spinal Cord - cytology
Survival Analysis
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Summary:Glial cell line-derived neurotrophic factor (GDNF), a member of the TG F-beta superfamily, has been shown to be a highly potent neurotrophic factor that enhances survival of various neuronal cell types including motoneurons. To assess its therapeutic potential in treating neurodegenerative diseases such as amyotrophic lateral sclerosis, we treated mutant mice displaying motoneuron degeneration (progressive motor neuropathy; pmn) with encapsulated GDNF-secreting cells. Effects of GDNF treatment on pmn/pmn mice were compared with previous results obtained with ciliary neurotrophic factor (CNTF) [Sagot Y, Tan SA, Baetge E, Schmalbruch H, Kato AC, Aebischer P (1995) Eur J Neurosci 7:1313-1322]. In contrast to CNTF, GDNF did not increase the lifespan of pmn/pmn mice. However, GDNF significantly reduced the loss of facial motoneurons by 50%, a value similar to what was observed when CNTF was administered to the pmn/pmn mice. Surprisingly, myelinated axon counts revealed that GDNF had no effect on nerve degeneration. Therefore, despite its potential in rescuing motoneuron cell bodies, the inability of GDNF to prevent nerve degeneration in pmn/pmn mice suggests that its usefulness in the treatment of motor neuron diseases may be restricted to cotreatment with other factors that act on the nerve process.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.16-07-02335.1996