Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy

@article{Sendtner1992CiliaryNF,
  title={Ciliary neurotrophic factor prevents degeneration of motor neurons in mouse mutant progressive motor neuronopathy},
  author={Michael Sendtner and Henning Schmalbruch and Kurt A. St{\"o}ckli and Patrick Carroll and Georg W. Kreutzberg and Hans Thoenen},
  journal={Nature},
  year={1992},
  volume={358},
  pages={502-504}
}
CILIARY neurotrophic factor (CNTF) supports the survival of embryonic motor neurons in vitro1,2 and in vivo3, and prevents lesion-mediated degeneration of rat motor neurons during early post-natal stages4. Here we report that CNTF greatly reduces all the functional and morphological changes in pmn/pmn mice5, an autosomal recessive mutant leading to progressive caudo-cranial motor neuron degeneration. The first manifestations of progressive motor neuronopathy in homozygous pmn/pmn mice become… Expand
Therapeutic benefit of ciliary neurotrophic factor in progressive motor neuronopathy depends on the route of delivery
TLDR
AdCNTF intramuscularly treated and intravenously treated pmn mice showed a 25% increase in mean life span and a reduced degeneration of phrenic myelinated nerve fibers, which correlated with elevated CNTF serum bioactivities. Expand
Ciliary neurotrophic factor-induced sprouting preserves motor function in a mouse model of mild spinal muscular atrophy.
TLDR
Findings indicate that ciliary neurotrophic factor is necessary for a sprouting response and thus enhances the size of motor units in skeletal muscles of Smn(+/-) mice, which could guide the way to new therapies for this motor neuron disease. Expand
Histometric effects of ciliary neurotrophic factor in wobbler mouse motor neuron disease
TLDR
It is suggested that ciliary neurotrophic factor slowed neuronal degeneration, enhanced axonal regeneration at both the proximal and distal motor axons, and reduced muscle atrophy in this motor neuron disease. Expand
Therapeutic benefits of cardiotrophin-1 gene transfer in a mouse model of spinal muscular atrophy.
TLDR
Intra-muscular injection of adenoviral vector expressing CT-1, even at very low dose, improves median survival, delays motor defect of mutant mice and exerts protective effect against loss of proximal motor axons and aberrant cytoskeletal organization of motor synaptic terminals. Expand
Inhibiting Axon Degeneration and Synapse Loss Attenuates Apoptosis and Disease Progression in a Mouse Model of Motoneuron Disease
TLDR
It is shown that the Wlds gene product attenuates symptoms, extends life span, prevents axon degeneration, rescues motoneuron number and size, and delays retrograde transport deficits in pmn/pmn mice, which suggest new pathogenic mechanisms and therapeutic avenues for mot oneuron diseases. Expand
Endogenous Ciliary Neurotrophic Factor Is a Lesion Factor for Axotomized Motoneurons in Adult Mice
TLDR
Ex vivo analysis of leukemia inhibitory factor mRNA expression revealed that endogenous LIF cannot compensate for the lack of CNTF in pmn crossbred with CNTF knock-out mice, and endogenous CNTF released from lesioned Schwann cells supports the survival of axotomized motoneurons under conditions in which motoneuron survival is in the process of rapid degeneration. Expand
Bcl-2 overexpression prevents motoneuron cell body loss but not axonal degeneration in a mouse model of a neurodegenerative disease
TLDR
The effects of Bcl-2 overexpression in a genetic mouse model with motor neuron disease (progressive motor neuronopathy/pmn) did not prevent degeneration of myelinated axons in the facial and phrenic motor nerves and it did not increase the life span of the animals. Expand
GDNF slows loss of motoneurons but not axonal degeneration or premature death of pmn/pmn mice
TLDR
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. Expand
Differential Effects of Neurotrophic Factors on Motoneuron Retrograde Labeling in a Murine Model of Motoneuron Disease
TLDR
The potential of neurotrophic factors to act on axonal transport properties in a mouse mutant, progressive motor neuronopathy (pmn), and the differential effects of these factors agree with previous studies showing that molecules that promote cell survival do not necessarily compensate for axonal deficiency. Expand
Neurotrophic Factors and Amyotrophic Lateral Sclerosis
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This review summarizes current findings on neurotrophic factor expression in ALS tissue and these factors’ potential/debatable clinical relevance to ALS and the treatment of ALS and discusses possible interventions improving clinical trial design to obtain efficacy of neurotrophic factors treatment in patients suffering from ALS. Expand
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TLDR
The disease manifests itself in a dying-back fashion in the distal portion of the motor neurons and may represent an animal model of hereditary motor neuron diseases in man. Expand
Ciliary neurotrophic factor prevents the degeneration of motor neurons after axotomy
TLDR
To determine whether the vulnerability of motor neurons to axotomy in the early postnatal phase is due to insufficient availability of ciliary neurotrophic factor, transected the axons of newborn rat motor neurons and demonstrated that local application of CNTF prevents the degeneration of the corresponding cell bodies. Expand
Effect of ciliary neurotrophic factor (CNTF) on motoneuron survival
Summary We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliaryExpand
Histopathology of the late-onset motor neuron degeneration (Mnd) mutant in the mouse.
The motor neuron degeneration (Mnd) is characterized by a progressive deterioration of motor function (stiff-legged gait, abnormal limb placements and grasping, and finally paralysis; moving fromExpand
Control of embryonic motoneuron survival in vivo by ciliary neurotrophic factor.
TLDR
Results of in vitro studies suggest that ciliary neurotrophic factor may not act as a neurotrophic agent in vivo for those embryonic neurons (especially ciliary neurons) on which it acts in vitro, but may be required for in vivo survival of motoneurons. Expand
Survival effect of ciliary neurotrophic factor (CNTF) on chick embryonic motoneurons in culture: comparison with other neurotrophic factors and cytokines
TLDR
Retrograde labeling of the motoneurons prior to their isolation showed that there is more than an 80% enrichment for mot oneurons by the method used, and other neurotrophic factors had no survival effect at all, even at concentrations up to 10 micrograms/ml for NGF and BDNF. Expand
Loss of motor neurons from the median nerve motor nucleus of the mutant mouse ‘wobbler’
TLDR
It is concluded that the most active period in the expression of the wobbler phenotype is from 3 to 6 weeks of age. Expand
Autosomal dominance in a late-onset motor neuron disease in the mouse.
A late-onset neurological disease has been identified in a substrain of C57Bl/6 mice. The disorder is characterized by hindlimb weakness and ataxia starting at 5-11 months of age, progressing toExpand
An hereditary motor neurone disease with progressive denervation of muscle in the mouse: the mutant 'wobbler'.
TLDR
The clinical and pathological studies of an hereditary disease in mice in which the primary abnormality appears to be located in the perikaryon of motor neurones is described. Expand
Molecular cloning, expression and regional distribution of rat ciliary neurotrophic factor
TLDR
The complementary DNA-deduced amino-acid sequence and subsequent expression of cDNA clones covering the entire coding region in HeLa-cells indicate that CNTF is a cytosolic protein, and shows thatCNTF is not a target-derived neurotrophic factor. Expand
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