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Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury

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-estab...

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Autores principales: Swieck, Kristen, Conta-Steencken, Amanda, Middleton, Frank A., Siebert, Justin R., Osterhout, Donna J., Stelzner, Dennis J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421714/
https://www.ncbi.nlm.nih.gov/pubmed/30885135
http://dx.doi.org/10.1186/s12868-019-0491-y
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author Swieck, Kristen
Conta-Steencken, Amanda
Middleton, Frank A.
Siebert, Justin R.
Osterhout, Donna J.
Stelzner, Dennis J.
author_facet Swieck, Kristen
Conta-Steencken, Amanda
Middleton, Frank A.
Siebert, Justin R.
Osterhout, Donna J.
Stelzner, Dennis J.
author_sort Swieck, Kristen
collection PubMed
description 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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spelling pubmed-64217142019-03-28 Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury Swieck, Kristen Conta-Steencken, Amanda Middleton, Frank A. Siebert, Justin R. Osterhout, Donna J. Stelzner, Dennis J. BMC Neurosci Research Article 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. BioMed Central 2019-03-18 /pmc/articles/PMC6421714/ /pubmed/30885135 http://dx.doi.org/10.1186/s12868-019-0491-y Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Swieck, Kristen
Conta-Steencken, Amanda
Middleton, Frank A.
Siebert, Justin R.
Osterhout, Donna J.
Stelzner, Dennis J.
Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title_full Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title_fullStr Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title_full_unstemmed Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title_short Effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
title_sort effect of lesion proximity on the regenerative response of long descending propriospinal neurons after spinal transection injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421714/
https://www.ncbi.nlm.nih.gov/pubmed/30885135
http://dx.doi.org/10.1186/s12868-019-0491-y
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