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The Journal of Neuroscience, February 1, 1998, 18(3):1132-1141

Differential Effects of Neurotrophic Factors on Motoneuron Retrograde Labeling in a Murine Model of Motoneuron Disease

Yves Sagot¹, Thierry Rossé¹, Richard Vejsada², Daniel Perrelet¹, and Ann C. Kato¹

¹ Department of Pharmacology and Division of Clinical Neuromuscular Research, Faculty of Medicine, Geneva University, 1211 Geneva 4, Switzerland, and ² Institute of Physiology, Czech Academy of Sciences, 14220 Prague 4, Czech Republic

It has been shown that abnormalities in axonal transport occur in several mouse models with motoneuron degeneration and also in the human disease amyotrophic lateral sclerosis. In this report, we have examined the potential of neurotrophic factors to act on axonal transport properties in a mouse mutant, progressive motor neuronopathy (pmn). This mouse mutant has been characterized as a "dying-back" motoneuronopathy, with a loss of motoneuron cell bodies and motor fibers. Retrograde transport to the spinal cord motoneurons was determined using fluorescent tracers either injected into the gastrocnemius muscle or applied directly onto the cut sciatic nerve. Because the rate of retrograde labeling was significantly reduced in the pmn, we examined the potential of neurotrophic factors to compensate for the impairment. Ciliary neurotrophic factor (CNTF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) but not glial-derived neurotrophic factor (GDNF) or nerve growth factor (NGF) were capable of significantly improving the rate of labeling. The differential effects of these factors agree with previous studies showing that molecules that promote cell survival do not necessarily compensate for axonal deficiency. Because impairment of axonal properties appears as an early event in motoneuron pathology, our results may have important clinical implications in the treatment of motoneuron diseases.

Key words: progressive motor neuronopathy; pmn; neurotrophic factors; retrograde transport; motoneuron disease; ALS; motoneuron cell death

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Copyright © 1998 Society for Neuroscience  0270-6474/98/1831132-10$05.00/0

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