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Renée Morris - One of the best experts on this subject based on the ideXlab platform.
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Rat motor neurons caudal to a Rubrospinal Tract (RST) transection remain viable.
Neuroscience, 2017Co-Authors: Brandon M. Wild, Rahul Mohan, Renée MorrisAbstract:In the rat, the Rubrospinal Tract (RST) is a descending motor pathway involved in the production of skilled reaching movement. The RST originates in the red nucleus in the midbrain and runs down the spinal cord in the lateral most aspect of the dorsolateral funiculus (DLF). The RST makes monosynaptic contact with interneurons within the intermediate laminae of the cord, however a contingent of RST axons constitutes direct supraspinal input for spinal cord motor neurons. The current study investigated the effects of unilateral RST transection at cervical levels C3-4 on the population of motor neurons in both spinal segments C5-6 and L2-3. The total number of large, medium and small motor neurons in these segments was estimated with stereological techniques in both ventral horns at 1, 3, 7 and 14days post-injury. In both spinal cord segments under investigation, no change was detected in mean number of motor neurons over time, in either ventral horn. That the loss of direct supraspinal input resulting from the RST transection does not affect the viability of motor neurons caudal to the injury indicates that these neurons have the potential to be re-innervated, should the RST injury be repaired.
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Production of high quality brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) RNA from isolated populations of rat spinal cord motor neurons obtained by Laser Capture Microdissection (LCM).
Neuroscience letters, 2016Co-Authors: Prachi Mehta, Brian Premkumar, Renée MorrisAbstract:The mammalian central nervous system (CNS) is composed of multiple cellular elements, making it challenging to segregate one particular cell type to study their gene expression profile. For instance, as motor neurons represent only 5-10% of the total cell population of the spinal cord, meaningful transcriptional analysis on these neurons is almost impossible to achieve from homogenized spinal cord tissue. A major challenge faced by scientists is to obtain good quality RNA from small amounts of starting material. In this paper, we used Laser Capture Microdissection (LCM) techniques to identify and isolate spinal cord motor neurons. The present analysis revealed that perfusion with paraformaldehyde (PFA) does not alter RNA quality. RNA integrity numbers (RINs) of tissue samples from Rubrospinal Tract (RST)-transected, intact spinal cord or from whole spinal cord homogenate were all above 8, which indicates intact, high-quality RNA. Levels of mRNA for brain-derived neurotrophic factor (BDNF) or for its tropomyosin receptor kinase B (TrkB) were not affected by Rubrospinal Tract (RST) transection, a surgical procedure that deprive motor neurons from one of their main supraspinal input. The isolation of pure populations of neurons with LCM techniques allows for robust transcriptional characterization that cannot be achieved with spinal cord homogenates. Such preparations of pure population of motor neurons will provide valuable tools to advance our understanding of the molecular mechanisms underlying spinal cord injury and neuromuscular diseases. In the near future, LCM techniques might be instrumental to the success of gene therapy for these debilitating conditions.
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Impaired arpeggio movement in skilled reaching by Rubrospinal Tract lesions in the rat: a behavioral/anatomical fractionation.
Journal of neurotrauma, 2011Co-Authors: Renée Morris, Andrew P. Tosolini, Joshua D. Goldstein, Ian Q. WhishawAbstract:AbsTract Spinal cord injury damaging the Rubrospinal Tract (RST) interferes with skilled forelimb movement, but identification of the precise role of the RST in this behavior is impeded by the difficulty of surgically isolating the RST from other pathways running within the lateral funiculus (LF). The present study used a skilled reaching task and a behavioral/anatomical dissection method to identify the contribution of the RST to skilled forelimb movement. Rats were trained on the skilled reaching task and subjected to lesions of the LF. Based on histological evaluation, the animals were assigned to large, medium, or small LF lesion size groups. End point and arm/hand/digit movements were subsequently identified for each group. Success was impaired in all groups, but the impairment was not related to lesion size. Frame-by-frame qualitative analysis of the video recordings revealed that large LF lesions abolished the elements of digits close, digits open, arpeggio, grasp, supination 2, and release. Medium...
Paul Lingor - One of the best experts on this subject based on the ideXlab platform.
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aav mediated expression of bag1 and rock2 shrna promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury
Journal of Neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion. Understanding the mechanisms involved in neuronal survival and axonal regeneration after spinal cord injury (SCI) is pivotal for the development of new therapies. We showed that over-expression of BAG1 (Bcl-2-associated athanogene-1) and down-regulation of ROCK2 (Rho-associated protein kinase) improve neuronal survival and axonal sprouting after SCI. Our results imply that BAG1 and ROCK2 represent interesting molecular targets that can be used in future therapeutic strategies for the treatment of SCI. AAV = adeno-associated virus.
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AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury.
Journal of neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion.
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AAV‐mediated expression of BAG1 and ROCK2‐shRNA promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury
Journal of Neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion. Understanding the mechanisms involved in neuronal survival and axonal regeneration after spinal cord injury (SCI) is pivotal for the development of new therapies. We showed that over-expression of BAG1 (Bcl-2-associated athanogene-1) and down-regulation of ROCK2 (Rho-associated protein kinase) improve neuronal survival and axonal sprouting after SCI. Our results imply that BAG1 and ROCK2 represent interesting molecular targets that can be used in future therapeutic strategies for the treatment of SCI. AAV = adeno-associated virus.
Malleswari Challagundla - One of the best experts on this subject based on the ideXlab platform.
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aav mediated expression of bag1 and rock2 shrna promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury
Journal of Neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion. Understanding the mechanisms involved in neuronal survival and axonal regeneration after spinal cord injury (SCI) is pivotal for the development of new therapies. We showed that over-expression of BAG1 (Bcl-2-associated athanogene-1) and down-regulation of ROCK2 (Rho-associated protein kinase) improve neuronal survival and axonal sprouting after SCI. Our results imply that BAG1 and ROCK2 represent interesting molecular targets that can be used in future therapeutic strategies for the treatment of SCI. AAV = adeno-associated virus.
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AAV-mediated expression of BAG1 and ROCK2-shRNA promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury.
Journal of neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion.
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AAV‐mediated expression of BAG1 and ROCK2‐shRNA promote neuronal survival and axonal sprouting in a rat model of Rubrospinal Tract injury
Journal of Neurochemistry, 2015Co-Authors: Malleswari Challagundla, Thomas Ostendorf, Jan C Koch, Vinicius Toledo Ribas, Uwe Michel, Sebastian Kügler, Frank Bradke, Mathias Bähr, Hans Werner Muller, Paul LingorAbstract:A lesion to the rat Rubrospinal Tract is a model for traumatic spinal cord lesions and results in atrophy of the red nucleus neurons, axonal dieback, and locomotor deficits. In this study, we used adeno-associated virus (AAV)-mediated over-expression of BAG1 and ROCK2-shRNA in the red nucleus to trace [by co-expression of enhanced green fluorescent protein (EGFP)] and treat the Rubrospinal Tract after unilateral dorsal hemisection. We investigated the effects of targeted gene therapy on neuronal survival, axonal sprouting of the Rubrospinal Tract, and motor recovery 12 weeks after unilateral dorsal hemisection at Th8 in rats. In addition to the evaluation of BAG1 and ROCK2 as therapeutic targets in spinal cord injury, we aimed to demonstrate the feasibility and the limits of an AAV-mediated protein over-expression versus AAV.shRNA-mediated down-regulation in this traumatic CNS lesion model. Our results demonstrate that BAG1 and ROCK2-shRNA both promote neuronal survival of red nucleus neurons and enhance axonal sprouting proximal to the lesion. Understanding the mechanisms involved in neuronal survival and axonal regeneration after spinal cord injury (SCI) is pivotal for the development of new therapies. We showed that over-expression of BAG1 (Bcl-2-associated athanogene-1) and down-regulation of ROCK2 (Rho-associated protein kinase) improve neuronal survival and axonal sprouting after SCI. Our results imply that BAG1 and ROCK2 represent interesting molecular targets that can be used in future therapeutic strategies for the treatment of SCI. AAV = adeno-associated virus.
Paul D. Storer - One of the best experts on this subject based on the ideXlab platform.
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Treatment of chronically injured spinal cord with neurotrophic factors stimulates βII-tubulin and GAP-43 expression in Rubrospinal Tract neurons
Journal of neuroscience research, 2003Co-Authors: Paul D. Storer, Dirk Dolbeare, John D. HouleAbstract:Exogenous neurotrophic factors provided at a spinal cord injury site promote regeneration of chronically injured Rubrospinal Tract (RST) neurons into a peripheral nerve graft. The present study tested whether the response to neurotrophins is associated with changes in the expression of two regeneration-associated genes, βII-tubulin and growth-associated protein (GAP)-43. Adult female rats were subjected to a right full hemisection lesion via aspiration of the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel foam saturated in brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), or phosphate-buffered saline (PBS) was applied to the lesion site for 60 min. Using in situ hybridization, RST neurons were examined for changes in mRNA levels of βII-tubulin and GAP-43 at 1, 3, and 7 days after treatment. Based on analysis of gene expression in single cells, there was no effect of BDNF treatment on either βII-tubulin or GAP-43 mRNA expression at any time point. βII-Tubulin mRNA levels were enhanced significantly at 1 and 3 days in animals treated with GDNF relative to levels in animals treated with PBS. Treatment with GDNF did not affect GAP-43 mRNA levels at 1 and 3 days, but at 7 days there was a significant increase in mRNA expression. Interestingly, 7 days after GDNF treatment, the mean cell size of chronically injured RST neurons was increased significantly. Although GDNF and BDNF both promote axonal regeneration by chronically injured neurons, only GDNF treatment is associated with upregulation of βII-tubulin or GAP-43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons. © 2003 Wiley-Liss, Inc.
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Glial fibrillary acidic protein expression in the hamster red nucleus: effects of axotomy and testosterone treatment
Experimental neurology, 2003Co-Authors: Paul D. Storer, Kathryn J. JonesAbstract:Testosterone propionate (TP) administration coincident with facial nerve axotomy in the hamster attenuates glial fibrillary acidic protein (GFAP) expression in the facial nucleus that is normally increased following axotomy alone. This ability of TP to modulate astrocyte activity has been linked to the ability of steroid hormones to enhance the regenerative response of injured motor neurons. In an ongoing study designed to examine the potential influences of steroid hormones on centrally projecting motoneurons, the astrocyte reaction in the red nucleus was examined. In the present study, in situ hybridization was used to assess changes in GFAP mRNA in the hamster red nucleus following spinal cord injury (SCI) and TP treatment. Castrated male hamsters were subjected to right Rubrospinal Tract (RST) transection at spinal cord level T1, with half the animals implanted subcutaneously with Silastic capsules containing 100% crystalline TP and the remainder sham implanted. The uninjured red nucleus served as an internal control. Postoperative survival times were 1, 2, 7, and 14 days. Qualitative-quantitative analyses of emulsion autoradiograms were accomplished. Axotomy alone resulted in a significant but transient increase in GFAP mRNA levels at 2 days postoperative in the injured red nucleus compared with the contralateral uninjured red nucleus. However, in TP-treated animals, GFAP mRNA levels were no different than control levels at 2 dpo but were significantly increased at 7 dpo relative to contralateral control. Additionally, the increase in GFAP mRNA levels following TP treatment was significantly smaller than following axotomy alone. These data suggest that testosterone both delays and reduces the astrocytic reaction in the red nucleus following Rubrospinal Tract axotomy, and confirms a difference between peripheral and central glial responses to axotomy and steroid administration.
John D. Houle - One of the best experts on this subject based on the ideXlab platform.
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Treatment of chronically injured spinal cord with neurotrophic factors stimulates βII-tubulin and GAP-43 expression in Rubrospinal Tract neurons
Journal of neuroscience research, 2003Co-Authors: Paul D. Storer, Dirk Dolbeare, John D. HouleAbstract:Exogenous neurotrophic factors provided at a spinal cord injury site promote regeneration of chronically injured Rubrospinal Tract (RST) neurons into a peripheral nerve graft. The present study tested whether the response to neurotrophins is associated with changes in the expression of two regeneration-associated genes, βII-tubulin and growth-associated protein (GAP)-43. Adult female rats were subjected to a right full hemisection lesion via aspiration of the C3 spinal cord. A second aspiration lesion was made 4 weeks later and gel foam saturated in brain-derived neurotrophic factor (BDNF), glial cell-line derived neurotrophic factor (GDNF), or phosphate-buffered saline (PBS) was applied to the lesion site for 60 min. Using in situ hybridization, RST neurons were examined for changes in mRNA levels of βII-tubulin and GAP-43 at 1, 3, and 7 days after treatment. Based on analysis of gene expression in single cells, there was no effect of BDNF treatment on either βII-tubulin or GAP-43 mRNA expression at any time point. βII-Tubulin mRNA levels were enhanced significantly at 1 and 3 days in animals treated with GDNF relative to levels in animals treated with PBS. Treatment with GDNF did not affect GAP-43 mRNA levels at 1 and 3 days, but at 7 days there was a significant increase in mRNA expression. Interestingly, 7 days after GDNF treatment, the mean cell size of chronically injured RST neurons was increased significantly. Although GDNF and BDNF both promote axonal regeneration by chronically injured neurons, only GDNF treatment is associated with upregulation of βII-tubulin or GAP-43 mRNA. It is not clear from the present study how exogenous BDNF stimulates regrowth of injured axons. © 2003 Wiley-Liss, Inc.
