The Experts below are selected from a list of 19668 Experts worldwide ranked by ideXlab platform
Takayuki Itoh - One of the best experts on this subject based on the ideXlab platform.
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impaired Regenerative Response of primary sensory neurons in zpk dlk gene trap mice
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
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Impaired Regenerative Response of primary sensory neurons in ZPK/DLK gene-trap mice.
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
Peter Bannerman - One of the best experts on this subject based on the ideXlab platform.
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impaired Regenerative Response of primary sensory neurons in zpk dlk gene trap mice
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
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Impaired Regenerative Response of primary sensory neurons in ZPK/DLK gene-trap mice.
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
Dennis J. Stelzner - One of the best experts on this subject based on the ideXlab platform.
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Effect of lesion proximity on the Regenerative Response of long descending propriospinal neurons after spinal transection injury
BMC Neuroscience, 2019Co-Authors: Kristen Swieck, Amanda Conta-steencken, Frank A. Middleton, Justin R. Siebert, Donna J. Osterhout, Dennis J. StelznerAbstract:Background The spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T_10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial Regenerative Response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic Response, leading to cell death. LDPT neurons, on the other hand, show neither a Regenerative nor an apoptotic Response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular Response for LDPT neurons, one of which is the distance of the LDPT cell body from the T_10 lesion. In this study, we examined the molecular Response of LDPT neurons to axotomy caused by a proximal spinal cord lesion. Results Utilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust Responses in TPS neurons were analyzed 3 days following a T_2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential Response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T_10 spinal transection). The genetic Response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major Regenerative or apoptotic Response within the population of genes examined. Conclusions The data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a Regenerative Response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their Response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.
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Effect of lesion proximity on the Regenerative Response of long descending propriospinal neurons after spinal transection injury
BMC Neuroscience, 2019Co-Authors: Kristen Swieck, Amanda Conta-steencken, Frank A. Middleton, Justin R. Siebert, Donna J. Osterhout, Dennis J. StelznerAbstract:Background The spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T_10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial Regenerative Response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic Response, leading to cell death. LDPT neurons, on the other hand, show neither a Regenerative nor an apoptotic Response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular Response for LDPT neurons, one of which is the distance of the LDPT cell body from the T_10 lesion. In this study, we examined the molecular Response of LDPT neurons to axotomy caused by a proximal spinal cord lesion. Results Utilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust Responses in TPS neurons were analyzed 3 days following a T_2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential Response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T_10 spinal transection). The genetic Response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major Regenerative or apoptotic Response within the population of genes examined. Conclusions The data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a Regenerative Response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their Response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.
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Modification of the Regenerative Response of dorsal column axons by olfactory ensheathing cells or peripheral axotomy in adult rat
Experimental Neurology, 2004Co-Authors: Melissa R. Andrews, Dennis J. StelznerAbstract:The regeneration of sciatic-dorsal column (DC) axons following DC crush injury and treatment with olfactory ensheathing cells (OECs) and/or sciatic axotomy (“conditioning lesion”) was evaluated. Sciatic-DC axons were examined with a transganglionic tracer, cholera toxin conjugated to horseradish peroxidase, and evaluated at chronic time points, 2–26 weeks post-lesion. With DC injury alone (n = 7), sciatic-DC axons were localized to the caudal border of the lesion terminating in reactive end bulbs with no indication of growth into the lesion. In contrast, treatment with either a heterogeneous population of OECs (equal numbers of p75- and fibronectin-positive OECs) (n = 9) or an enriched population of OECs (75% p75-positive OECs) (n = 6) injected either directly into the lesion or 1-mm rostral and caudal to the injury, stimulated DC axon growth into the lesion. A similar Regenerative Response was observed with a conditioning lesion either concurrent to (n = 4) or 1 week before (n = 4) the DC injury. In either of the latter two paradigms, some DC axons grew across the injury, but no axons grew into the rostral intact spinal cord. Upon combining OEC treatment with the conditioning lesion (n = 21), the result was additive, increasing DC axon growth beyond the rostral border of the lesion in best cases. Additional factors that may limit DC regeneration were tested including formation of the glial scar (immunoreactivity to glial fibrillary acidic protein in astrocytes and to chondroitin sulfate proteoglycans), which remained similar between treated and untreated groups.
Aki Itoh - One of the best experts on this subject based on the ideXlab platform.
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impaired Regenerative Response of primary sensory neurons in zpk dlk gene trap mice
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
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Impaired Regenerative Response of primary sensory neurons in ZPK/DLK gene-trap mice.
Biochemical and Biophysical Research Communications, 2009Co-Authors: Aki Itoh, Makoto Horiuchi, Peter Bannerman, David E Pleasure, Takayuki ItohAbstract:Abstract Rapid and persistent activation of c-JUN is necessary for axonal regeneration after nerve injury, although upstream molecular events leading to c-JUN activation remain largely unknown. ZPK/DLK/MAP3K12 activates the c-Jun N-terminal kinase pathway at an apical level. We investigated axonal regeneration of the dorsal root ganglion (DRG) neurons of homozygous ZPK/DLK gene-trap mice. In vitro neurite extension assays using DRG explants from 14 day-old mice revealed that neurite growth rates of the ZPK/DLK gene-trap DRG explants were reduced compared to those of the wild-type DRG explants. Three ZPK/DLK gene-trap mice which survived into adulthood were subjected to sciatic nerve axotomy. At 24 h after axotomy, phosphorylated c-JUN-positive DRG neurons were significantly less frequent in ZPK/DLK gene-trap mice than in wild-type mice. These results indicate that ZPK/DLK is involved in Regenerative Responses of mammalian DRG neurons to axonal injury through activation of c-JUN.
Kristen Swieck - One of the best experts on this subject based on the ideXlab platform.
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Effect of lesion proximity on the Regenerative Response of long descending propriospinal neurons after spinal transection injury
BMC Neuroscience, 2019Co-Authors: Kristen Swieck, Amanda Conta-steencken, Frank A. Middleton, Justin R. Siebert, Donna J. Osterhout, Dennis J. StelznerAbstract:Background The spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T_10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial Regenerative Response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic Response, leading to cell death. LDPT neurons, on the other hand, show neither a Regenerative nor an apoptotic Response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular Response for LDPT neurons, one of which is the distance of the LDPT cell body from the T_10 lesion. In this study, we examined the molecular Response of LDPT neurons to axotomy caused by a proximal spinal cord lesion. Results Utilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust Responses in TPS neurons were analyzed 3 days following a T_2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential Response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T_10 spinal transection). The genetic Response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major Regenerative or apoptotic Response within the population of genes examined. Conclusions The data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a Regenerative Response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their Response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.
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Effect of lesion proximity on the Regenerative Response of long descending propriospinal neurons after spinal transection injury
BMC Neuroscience, 2019Co-Authors: Kristen Swieck, Amanda Conta-steencken, Frank A. Middleton, Justin R. Siebert, Donna J. Osterhout, Dennis J. StelznerAbstract:Background The spinal cord is limited in its capacity to repair after damage caused by injury or disease. However, propriospinal (PS) neurons in the spinal cord have demonstrated a propensity for axonal regeneration after spinal cord injury. They can regrow and extend axonal projections to re-establish connections across a spinal lesion. We have previously reported differential reactions of two distinct PS neuronal populations—short thoracic propriospinal (TPS) and long descending propriospinal tract (LDPT) neurons—following a low thoracic (T_10) spinal cord injury in a rat model. Immediately after injury, TPS neurons undergo a strong initial Regenerative Response, defined by the upregulation of transcripts to several growth factor receptors, and growth associated proteins. Many also initiate a strong apoptotic Response, leading to cell death. LDPT neurons, on the other hand, show neither a Regenerative nor an apoptotic Response. They show either a lowered expression or no change in genes for a variety of growth associated proteins, and these neurons survive for at least 2 months post-axotomy. There are several potential explanations for this lack of cellular Response for LDPT neurons, one of which is the distance of the LDPT cell body from the T_10 lesion. In this study, we examined the molecular Response of LDPT neurons to axotomy caused by a proximal spinal cord lesion. Results Utilizing laser capture microdissection and RNA quantification with branched DNA technology, we analyzed the change in gene expression in LDPT neurons following axotomy near their cell body. Expression patterns of 34 genes selected for their robust Responses in TPS neurons were analyzed 3 days following a T_2 spinal lesion. Our results show that after axonal injury nearer their cell bodies, there was a differential Response of the same set of genes evaluated previously in TPS neurons after proximal axotomy, and LDPT neurons after distal axotomy (T_10 spinal transection). The genetic Response was much less robust than for TPS neurons after proximal axotomy, included both increased and decreased expression of certain genes, and did not suggest either a major Regenerative or apoptotic Response within the population of genes examined. Conclusions The data collectively demonstrate that the location of axotomy in relation to the soma of a neuron has a major effect on its ability to mount a Regenerative Response. However, the data also suggest that there are endogenous differences in the LDPT and TPS neuronal populations that affect their Response to axotomy. These phenotypic differences may indicate that different or multiple therapies may be needed following spinal cord injury to stimulate maximal regeneration of all PS axons.
