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Ronald M. Lindsay - One of the best experts on this subject based on the ideXlab platform.
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Ciliary Neurotrophic Factor protects striatal output neurons in an animal model of Huntington disease.
Proceedings of the National Academy of Sciences of the United States of America, 1996Co-Authors: Keith D. Anderson, Ronald M. Lindsay, Nikos Panayotatos, T. L. Corcoran, Stanley J. WiegandAbstract:Abstract Huntington disease is a dominantly inherited, untreatable neurological disorder featuring a progressive loss of striatal output neurons that results in dyskinesia, cognitive decline, and, ultimately, death. Neurotrophic Factors have recently been shown to be protective in several animal models of neurodegenerative disease, raising the possibility that such substances might also sustain the survival of compromised striatal output neurons. We determined whether intracerebral administration of brain-derived Neurotrophic Factor, nerve growth Factor, neurotrophin-3, or Ciliary Neurotrophic Factor could protect striatal output neurons in a rodent model of Huntington disease. Whereas treatment with brain-derived Neurotrophic Factor, nerve growth Factor, or neurotrophin-3 provided no protection of striatal output neurons from death induced by intrastriatal injection of quinolinic acid, an N-methyl-D-aspartate glutamate receptor agonist, treatment with Ciliary Neurotrophic Factor afforded marked protection against this neurodegenerative insult.
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histometric effects of Ciliary Neurotrophic Factor in wobbler mouse motor neuron disease
Annals of Neurology, 1995Co-Authors: Ken Ikeda, Ronald M. Lindsay, Vivien Wong, Thomas H Holmlund, Tom Greene, Jesse M Cedarbaum, Hiroshi MitsumotoAbstract:We investigated the histological effects of Ciliary Neurotrophic Factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human Ciliary Neurotrophic Factor (or a vehicle solution), 1-mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene--related peptide was higher in mice receiving rat Ciliary Neurotrophic Factor (p < 0.03), although the number of choline acetyltransferase-reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human Ciliary Neurotrophic Factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In Ciliary Neurotrophic Factor-treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end-plates were also higher in the Ciliary Neurotrophic Factor-treated mice (p < 0.001 and p < 0.02, respectively). Our study thus suggests 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.
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the effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease
Annals of Neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p<0.001), grip strength normalized to body weight in the Factor-treated mice was significantly greater (p<0.02) and declined at a slower rate (p<0.05) compared to that in vehicle-treated animals
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trophic effect of Ciliary Neurotrophic Factor on denervated skeletal muscle
Cell, 1994Co-Authors: Maureen E. Helgren, Ronald M. Lindsay, David J. Parry, George D. Yancopoulos, Stephen P Squinto, Heather L Davis, Teri G Boulton, Carol S Heck, Peter S DistefanoAbstract:Abstract The actions and receptor for Ciliary Neurotrophic Factor (CNTF) are largely restricted to cells of the nervous system, although one of the CNTF receptor components, CNTFRα, is expressed by skeletal muscle. Here we show that the other CNTF receptor components, LIFRβ and gp130, are also expressed by skeletal muscle and that expression of all three CNTF receptor components is greatly increased in denervated muscle. In vivo, administration of CNTF activates these receptors on skeletal muscle by inducing receptor phosphorylation and immediate-early gene responses. Furthermore, CNTF reduces the denervation-induced atrophy of muscle and attenuates the reduced twitch and tetanic tensions that result from muscle denervation. Our findings reveal that, in addition to its known Neurotrophic actions, CNTF exerts myotrophic effects by attenuating the morphological and functional changes associated with denervation of rat skeletal muscle.
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The effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease.
Annals of neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p
Hiroshi Mitsumoto - One of the best experts on this subject based on the ideXlab platform.
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histometric effects of Ciliary Neurotrophic Factor in wobbler mouse motor neuron disease
Annals of Neurology, 1995Co-Authors: Ken Ikeda, Ronald M. Lindsay, Vivien Wong, Thomas H Holmlund, Tom Greene, Jesse M Cedarbaum, Hiroshi MitsumotoAbstract:We investigated the histological effects of Ciliary Neurotrophic Factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human Ciliary Neurotrophic Factor (or a vehicle solution), 1-mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene--related peptide was higher in mice receiving rat Ciliary Neurotrophic Factor (p < 0.03), although the number of choline acetyltransferase-reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human Ciliary Neurotrophic Factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In Ciliary Neurotrophic Factor-treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end-plates were also higher in the Ciliary Neurotrophic Factor-treated mice (p < 0.001 and p < 0.02, respectively). Our study thus suggests 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.
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the effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease
Annals of Neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p<0.001), grip strength normalized to body weight in the Factor-treated mice was significantly greater (p<0.02) and declined at a slower rate (p<0.05) compared to that in vehicle-treated animals
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The effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease.
Annals of neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p
Christian C. Naus - One of the best experts on this subject based on the ideXlab platform.
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The complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor receptor α up-regulates connexin43 and intercellular coupling in astrocytes via the Janus tyrosine kinase/signal transducer and activator of transcription pathway
Molecular biology of the cell, 2004Co-Authors: Mark A. Ozog, Suzanne M. Bernier, Dave C. Bates, Bishwanath Chatterjee, Christian C. NausAbstract:Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of Ciliary Neurotrophic Factor (CNTF) on connexin43 (Cx43) expression and intercellular coupling in astrocytes. Murine cortical astrocytes matured in vitro were treated with CNTF (20 ng/ml), soluble Ciliary Neurotrophic Factor receptor alpha (CNTFRalpha) (200 ng/ml), or CNTF-CNTFRalpha. Although CNTF and CNTFRalpha alone had no effect on Cx43 expression, the heterodimer CNTF-CNTFRalpha significantly increased both Cx43 mRNA and protein levels. Cx43 immunostaining correlated with increased intercellular coupling as determined by dye transfer analysis. By using the pharmacological inhibitor alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide (AG490), the increase in Cx43 was found to be dependent on the Janus tyrosine kinase/signal transducer and activator of transcription (JAK/STAT) pathway. Immunocytochemical analysis revealed that CNTF-CNTFRalpha treatment produced nuclear localization of phosphorylated STAT3, whereas CNTF treatment alone did not. Transient transfection of constructs containing various sequences of the Cx43 promoter tagged to a LacZ reporter into ROS 17/2.8 cells confirmed that the promoter region between -838 to -1693 was deemed necessary for CNTF-CNTFRalpha to induce heightened expression. CNTF-CNTFRalpha did not alter Cx30 mRNA levels, suggesting selectivity of CNTF-CNTFRalpha for connexin signaling. Together in the presence of soluble receptor, CNTF activates the JAK/STAT pathway leading to enhanced Cx43 expression and intercellular coupling.
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The complex of Ciliary Neurotrophic Factor-Ciliary Neurotrophic Factor receptor α up-regulates connexin43 and intercellular coupling in astrocytes via the Janus tyrosine kinase/signal transducer and activator of transcription pathway
Molecular biology of the cell, 2004Co-Authors: Mark A. Ozog, Suzanne M. Bernier, Dave C. Bates, Bishwanath Chatterjee, Christian C. NausAbstract:Cytokines regulate numerous cell processes, including connexin expression and gap junctional coupling. In this study, we examined the effect of Ciliary Neurotrophic Factor (CNTF) on connexin43 (Cx4...
Ken Ikeda - One of the best experts on this subject based on the ideXlab platform.
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histometric effects of Ciliary Neurotrophic Factor in wobbler mouse motor neuron disease
Annals of Neurology, 1995Co-Authors: Ken Ikeda, Ronald M. Lindsay, Vivien Wong, Thomas H Holmlund, Tom Greene, Jesse M Cedarbaum, Hiroshi MitsumotoAbstract:We investigated the histological effects of Ciliary Neurotrophic Factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human Ciliary Neurotrophic Factor (or a vehicle solution), 1-mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene--related peptide was higher in mice receiving rat Ciliary Neurotrophic Factor (p < 0.03), although the number of choline acetyltransferase-reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human Ciliary Neurotrophic Factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In Ciliary Neurotrophic Factor-treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end-plates were also higher in the Ciliary Neurotrophic Factor-treated mice (p < 0.001 and p < 0.02, respectively). Our study thus suggests 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.
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the effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease
Annals of Neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p<0.001), grip strength normalized to body weight in the Factor-treated mice was significantly greater (p<0.02) and declined at a slower rate (p<0.05) compared to that in vehicle-treated animals
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The effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease.
Annals of neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p
Vivien Wong - One of the best experts on this subject based on the ideXlab platform.
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histometric effects of Ciliary Neurotrophic Factor in wobbler mouse motor neuron disease
Annals of Neurology, 1995Co-Authors: Ken Ikeda, Ronald M. Lindsay, Vivien Wong, Thomas H Holmlund, Tom Greene, Jesse M Cedarbaum, Hiroshi MitsumotoAbstract:We investigated the histological effects of Ciliary Neurotrophic Factor on degenerating motor neurons, their axons, and skeletal muscles in 68 wobbler mice with motor neuron disease. Treatment consisted of recombinant rat or human Ciliary Neurotrophic Factor (or a vehicle solution), 1-mg/kg subcutaneous injection, three times per week for 4 weeks after the clinical diagnosis. The number of motor neurons immunoreactive for calcitonin gene--related peptide was higher in mice receiving rat Ciliary Neurotrophic Factor (p < 0.03), although the number of choline acetyltransferase-reactive neurons was the same in both treated and untreated control groups. Treatment did not prevent vacuolar degeneration of motor neurons. In mice treated with human Ciliary Neurotrophic Factor, the percentage of axons undergoing acute axonal degeneration (myelin ovoids) was smaller in the entire C5 ventral root (p < 0.02) and in the musculocutaneous nerve (p < 0.04), and the number of myelinated nerve fibers was 30% higher in both nerves (p < 0.01 and p < 0.04, respectively) than in controls. In Ciliary Neurotrophic Factor-treated mice, the biceps muscle weight was 20% greater, the mean muscle fiber diameter was 30% larger, and the number of atrophied muscle fibers was 75% lower than that in the vehicle-treated wobbler mice (p < 0.001 for all three results). The number of terminal axonal branching points and the mean length of motor end-plates were also higher in the Ciliary Neurotrophic Factor-treated mice (p < 0.001 and p < 0.02, respectively). Our study thus suggests 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.
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the effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease
Annals of Neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p<0.001), grip strength normalized to body weight in the Factor-treated mice was significantly greater (p<0.02) and declined at a slower rate (p<0.05) compared to that in vehicle-treated animals
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The effects of Ciliary Neurotrophic Factor on motor dysfunction in wobbler mouse motor neuron disease.
Annals of neurology, 1994Co-Authors: Hiroshi Mitsumoto, Ken Ikeda, Vivien Wong, Tom Greene, Jesse M Cedarbaum, Tomas Holmlund, Ronald M. LindsayAbstract:Ciliary Neurotrophic Factor is the first Neurotrophic Factor to show survival-promoting effects in developing motor neurons in vitro, in ovo, and in vivo. In the present study we tested the effects of recombinant rat or human Ciliary Neurotrophic Factor in the wobbler mouse model of motor neuron disease. Mice received 1 mg/kg of the Factor or a vehicle solution subcutaneously three times a week for 4 weeks, after the disease was diagnosed between the ages of 3 and 4 weeks. Although treatment with rat Ciliary Neurotrophic Factor (n=6) resulted in delayed weight gain (p
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the receptor for Ciliary Neurotrophic Factor
Science, 1991Co-Authors: Samuel Davis, Mark E. Furth, Vivien Wong, Thomas H Aldrich, David M Valenzuela, Stephen P Squinto, George D. YancopoulosAbstract:Although Neurotrophic Factors were originally isolated on the basis of their ability to support the survival of neurons, these molecules are now thought to influence many aspects of the development and maintenance of the nervous system. Identifying the receptors for these Neurotrophic Factors should aid in identifying the cells on which these Factors act and in understanding their precise mechanisms of action. A "tagged-ligand panning" procedure was used to clone a receptor for Ciliary Neurotrophic Factor (CNTF). This receptor is expressed exclusively within the nervous system and skeletal muscle. The CNTF receptor has a structure unrelated to the receptors utilized by the nerve growth Factor family of Neurotrophic molecules, but instead is most homologous to the receptor for a cytokine, interleukin-6. This similarity suggestes that the CNTF receptor, like the interleukin-6 receptor, requires a second, signal-transducing component. In contrast to all known receptors, the CNTF receptor is anchored to cell membranes by a glycosyl-phosphatidylinositol linkage.