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Alan Frazer - One of the best experts on this subject based on the ideXlab platform.
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vagal nerve stimulation rapidly activates brain derived Neurotrophic Factor Receptor trkb in rat brain
PLOS ONE, 2012Co-Authors: Havan Furmaga, Flavia Regina Carreno, Alan FrazerAbstract:Background Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived Neurotrophic Factor (BDNF) in brain or activate, via phosphorylation, its Receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Methods Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. Results All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. Conclusion VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs.
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Vagal nerve stimulation rapidly activates brain-derived Neurotrophic Factor Receptor TrkB in rat brain
PloS one, 2012Co-Authors: Havan Furmaga, Flavia Regina Carreno, Alan FrazerAbstract:Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived Neurotrophic Factor (BDNF) in brain or activate, via phosphorylation, its Receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs.
A. John Maclennan - One of the best experts on this subject based on the ideXlab platform.
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Muscle ciliary Neurotrophic Factor Receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesion.
The European journal of neuroscience, 2018Co-Authors: Nancy Lee, Carolyn E. Rydyznski, Rachel P. Spearry, A. John MaclennanAbstract:Expression of the ciliary Neurotrophic Factor (CNTF) Receptor essential ligand binding subunit, CNTF Receptor α (CNTFRα), is induced in motor neurons and skeletal muscle following peripheral nerve lesion. We previously found muscle CNTFRα promotes motor neuron axon regeneration post-lesion. Both nerve lesion and CNTF administration activate motor neuron signal transducer and activator of transcription 3 (STAT3), a transcription Factor implicated in axon growth, suggesting CNTF Receptors may contribute to the lesion-induced STAT3 activation. However, many Receptor types signal through STAT3, and if CNTF Receptors contribute, motor neuron Receptors seemed most likely to regulate motor neuron STAT3. To determine the role played by muscle CNTFRα, we used in vivo, muscle-specific CNTFRα depletion in mice and report here that this selectively impairs the second phase, sustained motor neuron STAT3 activation post-lesion. Thus, muscle CNTFRα makes an essential contribution to motor neuron STAT3 activation during axon regeneration and may thereby promote axon regeneration through such signaling. We also report CNTFRα quantitative PCR suggesting involvement of many denervated muscle types, as well as muscle damaged at the lesion site. The present data add to the evidence suggesting that enhancing muscle CNTFRα expression may promote motor neuron regeneration in trauma and disease.
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Muscle and motor neuron ciliary Neurotrophic Factor Receptor α together maintain adult motor neuron axons in vivo.
European Journal of Neuroscience, 2016Co-Authors: Carolyn R. Serbinski, Makayla R. Braunlin, Matthew S. Rasch, Carolyn E. Rydyznski, A. John MaclennanAbstract:The molecular mechanisms maintaining adult motor innervation are comparatively unexplored relative to those involved during development. In addition to the fundamental neuroscience question, this area has important clinical ramifications given that loss of neuromuscular contact is thought to underlie several adult onset human neuromuscular diseases including amyotrophic lateral sclerosis. Indirect evidence suggests that ciliary Neurotrophic Factor (CNTF) Receptors may contribute to adult motor neuron axon maintenance. To directly address this in vivo, we used adult onset mouse genetic disruption techniques to deplete motor neuron and muscle CNTF Receptor α (CNTFRα), the essential ligand binding subunit of the Receptor, and incorporated reporters labelling affected motor neuron axons and terminals. The combined depletion of motor neuron and muscle CNTFRα produced a large loss of motor neuron terminals and retrograde labelling of motor neurons with FluoroGold indicated axon die-back well beyond muscle, together revealing an essential role for CNTFRα in adult motor axon maintenance. In contrast, selective depletion of motor neuron CNTFRα did not affect motor innervation. These data, along with our previous work indicating no effect of muscle specific CNTFRα depletion on motor innervation, suggest that motor neuron and muscle CNTFRα function in concert to maintain motor neuron axons. The data also raise the possibility of motor neuron and/or muscle CNTFRα as therapeutic targets for adult neuromuscular denervating diseases.
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Muscle ciliary Neurotrophic Factor Receptor α promotes axonal regeneration and functional recovery following peripheral nerve lesion.
The Journal of comparative neurology, 2013Co-Authors: Nancy Y. Lee, Myra K. Batt, Dennis S. Trinh, Carter O. Mason, Rachel P. Spearry, Rachel A Robitz, Kendra M. Leahy, Rebekah J. Zurbrugg, Richard J. Paul, A. John MaclennanAbstract:Ciliary Neurotrophic Factor (CNTF) administration maintains, protects, and promotes the regeneration of both motor neurons (MNs) and skeletal muscle in a wide variety of models. Expression of CNTF Receptor α (CNTFRα), an essential CNTF Receptor component, is greatly increased in skeletal muscle following neuromuscular insult. Together the data suggest that muscle CNTFRα may contribute to neuromuscular maintenance, protection, and/or regeneration in vivo. To directly address the role of muscle CNTFRα, we selectively-depleted it in vivo by using a “floxed” CNTFRα mouse line and a gene construct (mlc1f-Cre) that drives the expression of Cre specifically in skeletal muscle. The resulting mice were challenged with sciatic nerve crush. Counting of nerve axons and retrograde tracing of MNs indicated that muscle CNTFRα contributes to MN axonal regeneration across the lesion site. Walking track analysis indicated that muscle CNTFRα is also required for normal recovery of motor function. However, the same muscle CNTFRα depletion unexpectedly had no detected effect on the maintenance or regeneration of the muscle itself, even though exogenous CNTF has been shown to affect these functions. Similarly, MN survival and lesion-induced terminal sprouting were unaffected. Therefore, muscle CNTFRα is an interesting new example of a muscle growth Factor Receptor that, in vivo under physiological conditions, contributes much more to neuronal regeneration than to the maintenance or regeneration of the muscle itself. This novel form of muscle–neuron interaction also has implications in the therapeutic targeting of the neuromuscular system in MN disorders and following nerve injury.
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Regulation of ciliary Neurotrophic Factor Receptor α in sciatic motor neurons following axotomy
Neuroscience, 1999Co-Authors: A. John Maclennan, B.k. Devlin, K.l. Neitzel, D.l. Mclaurin, Kevin J. Anderson, Nancy LeeAbstract:Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of Neurotrophic Factors and corresponding Receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary Neurotrophic Factor Receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary Neurotrophic Factor Receptor alpha in axotomized sciatic motor neurons. Ciliary Neurotrophic Factor Receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary Neurotrophic Factor Receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary Neurotrophic Factor Receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary Neurotrophic Factor Receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary Neurotrophic Factor Receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary Neurotrophic Factor Receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of ciliary Neurotrophic Factor Receptor alpha protein in response to injury. Moreover, they suggest that the ability of a subpopulation of spinal motor neurons to regulate ciliary Neurotrophic Factor Receptor alpha levels in response to injury may play a role in their survival and axonal regeneration. Consistent with such a role, we also find relatively high, and probably elevated, levels of ciliary Neurotrophic Factor Receptor alpha immunoreactivity in regenerating axons.
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Ciliary Neurotrophic Factor Receptor alpha in spinal motoneurons is regulated by gonadal hormones.
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1998Co-Authors: Nancy G. Forger, Christine K. Wagner, Michael Contois, Lynn Bengston, A. John MaclennanAbstract:Ciliary Neurotrophic Factor Receptor alpha (CNTFRalpha) is the ligand-binding component of the CNTF Receptor. CNTFRalpha expression is essential for the normal development of spinal motoneurons and is required for the development of a sex difference in motoneuron number in androgen-sensitive perineal motoneurons. We used immunocytochemistry to examine the expression and hormone regulation of CNTFRalpha protein in the spinal nucleus of the bulbocavernosus (SNB), dorsolateral nucleus and retrodorsolateral nucleus of the lower lumbar spinal cord of adult rats. CNTFRalpha immunoreactivity (CNTFRalpha-IR) was observed in the somata and dendrites of virtually all motoneurons. In all three motor pools, the intensity of motoneuron soma labeling was greatest among gonadally intact males and was reduced in females and gonadectomized males. The density of CNTFRalpha-IR in neuropil also tended to be highest in intact males. Short-term (2 d) testosterone propionate treatment reversed the decline in the density of soma labeling in the SNB of castrated males but did not reverse any other effects of castration. Long-term hormone treatment, achieved by implanting males with testosterone capsules at the time of gonadectomy, prevented the decline in soma labeling in all motor pools and partially prevented the decline in neuropil label caused by castration. We conclude that expression of CNTFRalpha protein is androgen-regulated in spinal motoneurons.
Nancy Lee - One of the best experts on this subject based on the ideXlab platform.
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Muscle ciliary Neurotrophic Factor Receptor α contributes to motor neuron STAT3 activation following peripheral nerve lesion.
The European journal of neuroscience, 2018Co-Authors: Nancy Lee, Carolyn E. Rydyznski, Rachel P. Spearry, A. John MaclennanAbstract:Expression of the ciliary Neurotrophic Factor (CNTF) Receptor essential ligand binding subunit, CNTF Receptor α (CNTFRα), is induced in motor neurons and skeletal muscle following peripheral nerve lesion. We previously found muscle CNTFRα promotes motor neuron axon regeneration post-lesion. Both nerve lesion and CNTF administration activate motor neuron signal transducer and activator of transcription 3 (STAT3), a transcription Factor implicated in axon growth, suggesting CNTF Receptors may contribute to the lesion-induced STAT3 activation. However, many Receptor types signal through STAT3, and if CNTF Receptors contribute, motor neuron Receptors seemed most likely to regulate motor neuron STAT3. To determine the role played by muscle CNTFRα, we used in vivo, muscle-specific CNTFRα depletion in mice and report here that this selectively impairs the second phase, sustained motor neuron STAT3 activation post-lesion. Thus, muscle CNTFRα makes an essential contribution to motor neuron STAT3 activation during axon regeneration and may thereby promote axon regeneration through such signaling. We also report CNTFRα quantitative PCR suggesting involvement of many denervated muscle types, as well as muscle damaged at the lesion site. The present data add to the evidence suggesting that enhancing muscle CNTFRα expression may promote motor neuron regeneration in trauma and disease.
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Ciliary Neurotrophic Factor Receptor Regulation of Adult Forebrain Neurogenesis
The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013Co-Authors: Nancy Lee, Myra K. Batt, Brigitte A. Cronier, Michele C. Jackson, Jennifer L. Garza, Dennis S. Trinh, Carter O. Mason, Rachel P. Spearry, Shayon Bhattacharya, Rachel A RobitzAbstract:Appropriately targeted manipulation of endogenous neural stem progenitor (NSP) cells may contribute to therapies for trauma, stroke, and neurodegenerative disease. A prerequisite to such therapies is a better understanding of the mechanisms regulating adult NSP cells in vivo. Indirect data suggest that endogenous ciliary Neurotrophic Factor (CNTF) Receptor signaling may inhibit neuronal differentiation of NSP cells. We challenged subventricular zone (SVZ) cells in vivo with low concentrations of CNTF to anatomically characterize cells containing functional CNTF Receptors. We found that type B "stem" cells are highly responsive, whereas type C "transit-amplifying" cells and type A neuroblasts are remarkably unresponsive, as are GFAP(+) astrocytes found outside the SVZ. CNTF was identified in a subset of type B cells that label with acute BrdU administration. Disruption of in vivo CNTF Receptor signaling in SVZ NSP cells, with a "floxed" CNTF Receptor α (CNTFRα) mouse line and a gene construct driving Cre recombinase (Cre) expression in NSP cells, led to increases in SVZ-associated neuroblasts and new olFactory bulb neurons, as well as a neuron subtype-specific, adult-onset increase in olFactory bulb neuron populations. Adult-onset Receptor disruption in SVZ NSP cells with a recombinant adeno-associated virus (AAV-Cre) also led to increased neurogenesis. However, the maintenance of type B cell populations was apparently unaffected by the Receptor disruption. Together, the data suggest that endogenous CNTF Receptor signaling in type B stem cells inhibits adult neurogenesis, and further suggest that the regulation may occur in a neuron subtype-specific manner.
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In vivo localization and characterization of functional ciliary Neurotrophic Factor Receptors which utilize JAK-STAT signaling.
Neuroscience, 2000Co-Authors: Aj Maclennan, B.k. Devlin, K.l. Neitzel, Jesús T. García, G.a Hauptman, Isabelle Gloaguen, A Di Marco, Ralph Laufer, Nancy LeeAbstract:Abstract The ciliary Neurotrophic Factor Receptor is critically involved in embryonic motor neuron development. Postnatally, it may contribute to neuronal maintenance and regeneration. In addition, pharmacological stimulation of the Receptor may slow the progression of several neurodegenerative disorders. The widespread nervous system expression of ciliary Neurotrophic Factor Receptor components and the effects of low ciliary Neurotrophic Factor concentrations on a wide variety of cells in culture combine to suggest that functional ciliary Neurotrophic Factor Receptors are expressed by many classes of neurons in vivo . However, the in vivo signaling properties and distribution of functional ciliary Neurotrophic Factor Receptors have not been directly determined. We developed a novel in vivo assay of functional ciliary Neurotrophic Factor Receptors which revealed that, in the adult nervous system, cranial and spinal motor neurons are very sensitive to ciliary Neurotrophic Factor and display a rapid, robust increase in phospho-STAT3 in their dendrites, cell bodies and nuclei, which is specifically blocked by the ciliary Neurotrophic Factor Receptor antagonist, AADH-CNTF. In distinct contrast, several other classes of ciliary Neurotrophic Factor Receptor expressing neurons fail to increase phospho-STAT3 levels following ciliary Neurotrophic Factor treatment, even when ciliary Neurotrophic Factor is applied at high concentrations. Leukemia inhibitory Factor and epidermal growth Factor elicit the same cell-type-dependent pattern of phospho-STAT3 increases. Responsive and non-responsive neurons express comparable levels of STAT3. Therefore, in vivo ciliary Neurotrophic Factor Receptor-initiated STAT3 signal transduction is regulated in a very cell-type-dependent manner. The present data suggest that at least some of this regulation occurs at the STAT3 tyrosine phosphorylation step. These unexpected results also suggest that other forms of Receptor-initiated STAT3 signal transduction may be similarly regulated.
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Regulation of ciliary Neurotrophic Factor Receptor α in sciatic motor neurons following axotomy
Neuroscience, 1999Co-Authors: A. John Maclennan, B.k. Devlin, K.l. Neitzel, D.l. Mclaurin, Kevin J. Anderson, Nancy LeeAbstract:Spinal motor neurons are one of the few classes of neurons capable of regenerating axons following axotomy. Injury-induced expression of Neurotrophic Factors and corresponding Receptors may play an important role in this rare ability. A wide variety of indirect data suggests that ciliary Neurotrophic Factor Receptor alpha may critically contribute to the regeneration of injured spinal motor neurons. We used immunohistochemistry, in situ hybridization and retrograde tracing techniques to study the regulation of ciliary Neurotrophic Factor Receptor alpha in axotomized sciatic motor neurons. Ciliary Neurotrophic Factor Receptor alpha immunoreactivity, detected with two independent antisera, is increased in a subpopulation of caudal sciatic motor neuron soma one, two and six weeks after sciatic nerve transection and reattachment, while no changes are detected at one day and 15 weeks post-lesion. Ciliary Neurotrophic Factor Receptor alpha messenger RNA levels are augmented in the same classes of neurons following an identical lesion, suggesting that increased synthesis contributes, at least in part, to the additional ciliary Neurotrophic Factor Receptor alpha protein. Separating the proximal and distal nerve stumps with a plastic barrier does not noticeably affect the injury-induced change in ciliary Neurotrophic Factor Receptor alpha regulation, thereby indicating that this injury response is not dependent on signals distal to the lesion traveling retrogradely through the nerve or signals generated by axonal growth through the distal nerve. The prolonged increases in ciliary Neurotrophic Factor Receptor alpha protein and messenger RNA found in regenerating sciatic motor neurons contrast with the responses of non-regenerating central neurons, which are reported to display, at most, a short-lived increase in ciliary Neurotrophic Factor Receptor alpha messenger RNA expression following injury. The present data are the first to demonstrate, in vivo, neuronal regulation of ciliary Neurotrophic Factor Receptor alpha protein in response to injury. Moreover, they suggest that the ability of a subpopulation of spinal motor neurons to regulate ciliary Neurotrophic Factor Receptor alpha levels in response to injury may play a role in their survival and axonal regeneration. Consistent with such a role, we also find relatively high, and probably elevated, levels of ciliary Neurotrophic Factor Receptor alpha immunoreactivity in regenerating axons.
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Immunohistochemical localization of ciliary Neurotrophic Factor Receptor alpha expression in the rat nervous system
The Journal of neuroscience : the official journal of the Society for Neuroscience, 1996Co-Authors: Aj Maclennan, D.l. Mclaurin, Emily N. Vinson, L Marks, M Pfeifer, Nancy LeeAbstract:Ciliary Neurotrophic Factor Receptor alpha (CNTFR alpha) is essential for normal embryonic development and may be involved in postnatal and adult neuronal maintenance. In addition, a rapidly growing body of evidence suggests that CNTFR alpha serves as a site of action for future growth Factor therapeutics capable of treating a wide variety of disorders resulting from neuronal loss. We raised two polyclonal, anti-CNTFR alpha antisera against synthetic peptides corresponding to independent regions of rat CNTFR alpha. Western blot and immunohistochemical analyses indicated that affinity-purified preparations of both antisera specifically recognize CNTFR alpha. In the adult brain, the highest levels of CNTFR alpha immunoreactivity were found in the perikarya, dendrites and, occasionally, the axons of several distinct classes of neurons including hippocampal formation neurons, some sensory neurons, and many neurons involved in motor control. CNTFR alpha immunoreactivity also was concentrated in the following: perikarya, dendrites, and axons of ventral horn motor neurons in adult spinal cord; perikarya and axons of adult dorsal root ganglion neurons; and axons in adult peripheral nerve. In embryonic tissue, the highest levels of CNTFR alpha immunoreactivity were observed in differentiating neurons and their processes. Therefore, the present data suggest that CNTFR alpha serves several diverse functions in adulthood and during development.
Havan Furmaga - One of the best experts on this subject based on the ideXlab platform.
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vagal nerve stimulation rapidly activates brain derived Neurotrophic Factor Receptor trkb in rat brain
PLOS ONE, 2012Co-Authors: Havan Furmaga, Flavia Regina Carreno, Alan FrazerAbstract:Background Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived Neurotrophic Factor (BDNF) in brain or activate, via phosphorylation, its Receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Methods Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. Results All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. Conclusion VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs.
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Vagal nerve stimulation rapidly activates brain-derived Neurotrophic Factor Receptor TrkB in rat brain
PloS one, 2012Co-Authors: Havan Furmaga, Flavia Regina Carreno, Alan FrazerAbstract:Vagal nerve stimulation (VNS) has been approved for treatment-resistant depression. Many antidepressants increase expression of brain-derived Neurotrophic Factor (BDNF) in brain or activate, via phosphorylation, its Receptor, TrkB. There have been no studies yet of whether VNS would also cause phosphorylation of TrkB. Western blot analysis was used to evaluate the phosphorylation status of TrkB in the hippocampus of rats administered VNS either acutely or chronically. Acute effects of VNS were compared with those caused by fluoxetine or desipramine (DMI) whereas its chronic effects were compared with those of sertraline or DMI. All treatments, given either acutely or chronically, significantly elevated phosphorylation of tyrosines 705 and 816 on TrkB in the hippocampus. However, only VNS increased the phosphorylation of tyrosine 515, with both acute and chronic administration causing this effect. Pretreatment with K252a, a nonspecific tyrosine kinase inhibitor, blocked the phosphorylation caused by acute VNS at all three tyrosines. Downstream effectors of Y515, namely Akt and ERK, were also phosphorylated after acute treatment with VNS, whereas DMI did not cause this effect. VNS rapidly activates TrkB phosphorylation and this effect persists over time. VNS-induced phosphorylation of tyrosine 515 is distinct from the effect of standard antidepressant drugs.
Karl Wah Keung Tsim - One of the best experts on this subject based on the ideXlab platform.
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Cloning of the α Component of the Chick Ciliary Neurotrophic Factor Receptor: Developmental Expression and Down-Regulation in Denervated Skeletal Muscle
Journal of neurochemistry, 2002Co-Authors: Karl Wah Keung TsimAbstract:A full-length cDNA clone encoding for the chick CNTFR alpha (alpha component of the ciliary Neurotrophic Factor Receptor) was isolated by screening an embryonic day 13 chick brain cDNA library with a rat CNTFR alpha probe. The isolated cDNA clone contained a approximately 2-kb insert with an open reading frame of 362 amino acids. The identification of this clone as chick CNTFR alpha was based on the homology in amino acid sequence (approximately 70%) with the rat and human CNTFR alpha. Hydropathy analysis revealed that the chick CNTFR alpha contains a hydrophobic region at the amino terminus that is typical of secretory signal peptides, as well as a hydrophobic region at the carboxyl terminus that is characteristic of glycosylphosphatidylinositol-linked proteins. The expression of chick CNTFR alpha was developmentally regulated and was widely distributed in neural tissues, such as brain and spinal cord. In the periphery, chick CNTFR alpha transcript was expressed at high levels in the skeletal muscle and was only barely detectable in the liver. Unexpectedly, the expression of chick CNTFR alpha mRNA in skeletal muscle was decreased by approximately 10-fold at 1.5 days after denervation. This is in sharp contrast to the result previously obtained with CNTFR alpha in denervated rat muscle.
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Differential expression of ciliary Neurotrophic Factor Receptor in skeletal muscle of chick and rat after nerve injury
Journal of neurochemistry, 2002Co-Authors: Karl Wah Keung TsimAbstract:The activities of ciliary Neurotrophic Factor (CNTF) were initially thought to be restricted to cells in the nervous system. However, the recent identification of its Receptor specificity-conferring alpha component (CNTFR alpha) in skeletal muscle has provided the clue to the unexpected actions of CNTF in the periphery. In the present study, we demonstrated that the mRNA expression of CNTFR alpha in chick skeletal muscle was decreased by approximately 10-fold after nerve transection; this finding is in sharp contrast to the dramatic up-regulation observed in denervated rat muscle. As a first step toward investigating the differential regulation of CNTFR alpha in chick and rat, we examined the mRNA expression of CNTFR alpha in different types of muscle following nerve injury in young and adult animals. Our findings demonstrated that the differential expression of CNTFR alpha observed in denervated skeletal muscle of the chick and rat was not dependent on age or muscle type. The temporal profile of the changes in CNTFR alpha expression was, however, dependent on the age of the chick as well as the types of muscles. Furthermore, the low level of CNTFR alpha expression observed in denervated chick muscle recovered to almost control levels in regenerating skeletal muscle. Taken together, our findings provided the first extensive analysis on the mRNA expression of CNTFR alpha and the alpha subunit of the acetylcholine Receptor in various skeletal muscles of the chick following nerve injury and regeneration.