Differential effects of neurotrophic factors on motoneuron retrograde labeling in a murine model of motoneuron disease.
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.
Sagot
Y
Y
Department of Pharmacology, Faculty of Medicine, Geneva University, 1211 Geneva 4, Switzerland.
Rossé
T
T
Vejsada
R
R
Perrelet
D
D
Kato
A C
AC
D000818:Animals; D001370:Axonal Transport / Q000235:genetics; D019771:Axotomy; D048588:Benzoxazines; D016923:Cell Death / Q000502:physiology; D004396:Coloring Agents; D004195:Disease Models, Animal; D005456:Fluorescent Dyes; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D051379:Mice; D008818:Mice, Neurologic Mutants; D008822:Mice, Transgenic; D016472:Motor Neuron Disease / Q000503:physiopathology*; D009046:Motor Neurons / Q000737:chemistry* / Q000187:drug effects* / Q000502:physiology; D009410:Nerve Degeneration / Q000503:physiopathology; D009414:Nerve Growth Factors / Q000494:pharmacology*; D010078:Oxazines; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics; D013266:Stilbamidines
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D048588:Benzoxazines; D004396:Coloring Agents; D005456:Fluorescent Dyes; D009414:Nerve Growth Factors; D010078:Oxazines; D019253:Proto-Oncogene Proteins c-bcl-2; D013266:Stilbamidines; C028911:cresyl violet