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Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury
BACKGROUND: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of mod...
Autores principales: | , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2010
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900267/ https://www.ncbi.nlm.nih.gov/pubmed/20534130 http://dx.doi.org/10.1186/1471-2164-11-365 |
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author | Ryge, Jesper Winther, Ole Wienecke, Jacob Sandelin, Albin Westerdahl, Ann-Charlotte Hultborn, Hans Kiehn, Ole |
author_facet | Ryge, Jesper Winther, Ole Wienecke, Jacob Sandelin, Albin Westerdahl, Ann-Charlotte Hultborn, Hans Kiehn, Ole |
author_sort | Ryge, Jesper |
collection | PubMed |
description | BACKGROUND: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. RESULTS: Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. CONCLUSIONS: This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. |
format | Text |
id | pubmed-2900267 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-29002672010-07-09 Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury Ryge, Jesper Winther, Ole Wienecke, Jacob Sandelin, Albin Westerdahl, Ann-Charlotte Hultborn, Hans Kiehn, Ole BMC Genomics Research Article BACKGROUND: Spinal cord injury leads to neurological dysfunctions affecting the motor, sensory as well as the autonomic systems. Increased excitability of motor neurons has been implicated in injury-induced spasticity, where the reappearance of self-sustained plateau potentials in the absence of modulatory inputs from the brain correlates with the development of spasticity. RESULTS: Here we examine the dynamic transcriptional response of motor neurons to spinal cord injury as it evolves over time to unravel common gene expression patterns and their underlying regulatory mechanisms. For this we use a rat-tail-model with complete spinal cord transection causing injury-induced spasticity, where gene expression profiles are obtained from labeled motor neurons extracted with laser microdissection 0, 2, 7, 21 and 60 days post injury. Consensus clustering identifies 12 gene clusters with distinct time expression profiles. Analysis of these gene clusters identifies early immunological/inflammatory and late developmental responses as well as a regulation of genes relating to neuron excitability that support the development of motor neuron hyper-excitability and the reappearance of plateau potentials in the late phase of the injury response. Transcription factor motif analysis identifies differentially expressed transcription factors involved in the regulation of each gene cluster, shaping the expression of the identified biological processes and their associated genes underlying the changes in motor neuron excitability. CONCLUSIONS: This analysis provides important clues to the underlying mechanisms of transcriptional regulation responsible for the increased excitability observed in motor neurons in the late chronic phase of spinal cord injury suggesting alternative targets for treatment of spinal cord injury. Several transcription factors were identified as potential regulators of gene clusters containing elements related to motor neuron hyper-excitability, the manipulation of which potentially could be used to alter the transcriptional response to prevent the motor neurons from entering a state of hyper-excitability. BioMed Central 2010-06-09 /pmc/articles/PMC2900267/ /pubmed/20534130 http://dx.doi.org/10.1186/1471-2164-11-365 Text en Copyright ©2010 Ryge et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Ryge, Jesper Winther, Ole Wienecke, Jacob Sandelin, Albin Westerdahl, Ann-Charlotte Hultborn, Hans Kiehn, Ole Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title | Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title_full | Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title_fullStr | Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title_full_unstemmed | Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title_short | Transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
title_sort | transcriptional regulation of gene expression clusters in motor neurons following spinal cord injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2900267/ https://www.ncbi.nlm.nih.gov/pubmed/20534130 http://dx.doi.org/10.1186/1471-2164-11-365 |
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