Muscle-derived neurotrophin-4 as an activity-dependent trophic signal for adult motor neurons.

The production of neurotrophin-4 (NT-4) in rat skeletal muscle was found to depend on muscle activity. The amounts of NT-4 messenger RNA present decreased after blockade of neuromuscular transmission with alpha-bungarotoxin and increased during postnatal development and after electrical stimulation in a dose-dependent manner. NT-4 immunoreactivity was detected in slow, type I muscle fibers. Intramuscular administration of NT-4 induced sprouting of intact adult motor nerves. Thus, muscle-derived NT-4 acted as an activity-dependent neurotrophic signal for growth and remodeling of adult motor neuron innervation. NT-4 may thus be partly responsible for the effects of exercise and electrical stimulation on neuromuscular performance.

[1]  R. Oppenheim,et al.  Brain-derived neurotrophic factor rescues developing avian motoneurons from cell death , 1992, Nature.

[2]  A L Connold,et al.  Effect of low calcium and protease inhibitors on synapse elimination during postnatal development in the rat soleus muscle. , 1986, Brain research.

[3]  R. L. Holland,et al.  Motor nerve sprouting. , 1981, Annual review of neuroscience.

[4]  M. Dennis.  Development of the neuromuscular junction: inductive interactions between cells. , 1981, Annual review of neuroscience.

[5]  M. Gurney,et al.  Induction of motor neuron sprouting in vivo by ciliary neurotrophic factor and basic fibroblast growth factor , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[6]  Jeff W. Lichtman,et al.  Long-term synapse loss induced by focal blockade of postsynaptlc receptors , 1994, Nature.

[7]  G. Yancopoulos,et al.  Neurotrophin-4 is a target-derived neurotrophic factor for neurons of the trigeminal ganglion. , 1993, Development.

[8]  S. McMahon,et al.  Neurotrophins promote motor neuron survival and are present in embryonic limb bud , 1993, Nature.

[9]  A. Wernig,et al.  Sprouting and remodelling at the nerve-muscle junction , 1986, Progress in Neurobiology.

[10]  J. Frisén,et al.  Differential expression of mRNAs for neurotrophins and their receptors after axotomy of the sciatic nerve , 1993, The Journal of cell biology.

[11]  RJ Balice-Gordon,et al.  In vivo visualization of the growth of pre- and postsynaptic elements of neuromuscular junctions in the mouse , 1990, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[12]  P. Ernfors,et al.  Cells Expressing mRNA for Neurotrophins and their Receptors During Embryonic Rat Development , 1992, The European journal of neuroscience.

[13]  D. Price,et al.  Neurotrophin 4/5 is a trophic factor for mammalian facial motor neurons. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[14]  W. Kraemer,et al.  The effects of exercise training of different intensities on neuromuscular junction morphology , 1993, Journal of neurocytology.

[15]  M. Smith,et al.  Retrograde signaling in the formation and maintenance of the neuromuscular junction. , 1994, Journal of neurobiology.

[16]  R. Clatterbuck,et al.  Evidence that brain-derived neurotrophic factor is a trophic factor for motor neurons in vivo , 1993, Neuron.

[17]  H. Thoenen,et al.  Brain-derived neurotrophic factor prevents the death of motoneurons in newborn rats after nerve section , 1992, Nature.

[18]  Yves-Alain Barde,et al.  Trophic factors and neuronal survival , 1989, Neuron.

[19]  H. Thoenen.  The changing scene of neurotrophic factors , 1991, Trends in Neurosciences.

[20]  W. Bradley,et al.  Morphometric and biochemical studies of peripheral nerves in amyotrophic lateral sclerosis , 1983, Annals of neurology.

[21]  J. Changeux,et al.  Denervation increases a neurite-promoting activity in extracts of skeletal muscle , 1983, Nature.

[22]  D. Kernell,et al.  Myofibrillar ATPase histochemistry of rat skeletal muscles: a "two-dimensional" quantitative approach. , 1991, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[23]  N. Ip,et al.  The Neurotrophins BDNF, NT‐3 and NT‐4/5, But Not NGF, Up‐regulate the Cholinergic Phenotype of Developing Motor Neurons , 1993, The European journal of neuroscience.

[24]  A. Connold,et al.  Neuromuscular contacts of expanded motor units in rat soleus muscles are rescued by leupeptin , 1994, Neuroscience.

[25]  P. Caroni,et al.  Role of muscle insulin-like growth factors in nerve sprouting: suppression of terminal sprouting in paralyzed muscle by IGF-binding protein 4 , 1994, The Journal of cell biology.

[26]  W. Snider,et al.  Brain-derived neurotrophic factor rescues spinal motor neurons from axotomy-induced cell death , 1992, Nature.

[27]  J. R. Slack,et al.  The sequential development of nodal sprouts in mouse muscles in response to nerve degeneration , 1981, Journal of neurocytology.

[28]  A. Irintchev,et al.  Axonal sprouting and changes in fibre types after running-induced muscle damage , 1991, Journal of neurocytology.

[29]  L. Landmesser.  The relationship of intramuscular nerve branching and synaptogenesis to motoneuron survival. , 1992, Journal of neurobiology.

[30]  T L Munsat,et al.  Effects of nerve stimulation on human muscle. , 1976, Archives of neurology.

[31]  N. Belluardo,et al.  Widespread and Developmentally Regulated Expression of Neurotrophin‐4 mRNA in Rat Brain and Peripheral Tissues , 1993, The European journal of neuroscience.