Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats

Serotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2A and 5-HT7 receptor...

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Main Authors: Krzysztof Miazga, Hanna Fabczak, Ewa Joachimiak, Małgorzata Zawadzka, Łucja Krzemień-Ojak, Marek Bekisz, Anna Bejrowska, Larry M. Jordan, Urszula Sławińska
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2018/4232706
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author Krzysztof Miazga
Hanna Fabczak
Ewa Joachimiak
Małgorzata Zawadzka
Łucja Krzemień-Ojak
Marek Bekisz
Anna Bejrowska
Larry M. Jordan
Urszula Sławińska
author_facet Krzysztof Miazga
Hanna Fabczak
Ewa Joachimiak
Małgorzata Zawadzka
Łucja Krzemień-Ojak
Marek Bekisz
Anna Bejrowska
Larry M. Jordan
Urszula Sławińska
author_sort Krzysztof Miazga
collection DOAJ
description Serotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2A and 5-HT7 receptors improves locomotor hindlimb movements in paraplegic rats. Here, we analyzed the mRNA of 5-HT2A and 5-HT7 receptors (encoded by Htr2a and Htr7 genes, resp.) in motoneurons innervating tibialis anterior (TA) and gastrocnemius lateralis (GM) hindlimb muscles and the tail extensor caudae medialis (ECM) muscle in intact as well as spinal rats. Moreover, the effect of intraspinal grafting of serotonergic neurons on Htr2a and Htr7 gene expression was examined to test the possibility that the graft origin 5-HT innervation in the spinal cord of paraplegic rats could reverse changes in gene expression induced by SCI. Our results indicate that SCI at the thoracic level leads to changes in Htr2a and Htr7 gene expression, whereas transplantation of embryonic serotonergic neurons modifies these changes in motoneurons innervating hindlimb muscles but not those innervating tail muscles. This suggests that the upregulation of genes critical for locomotor recovery, resulting in limb motoneuron plasticity, might account for the improved locomotion in grafted animals.
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spelling doaj-art-7463627a40044efba7be665c5cb1a24f2025-02-03T07:26:06ZengWileyNeural Plasticity2090-59041687-54432018-01-01201810.1155/2018/42327064232706Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic RatsKrzysztof Miazga0Hanna Fabczak1Ewa Joachimiak2Małgorzata Zawadzka3Łucja Krzemień-Ojak4Marek Bekisz5Anna Bejrowska6Larry M. Jordan7Urszula Sławińska8Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandDepartment of Physiology and Phatophysiology, University of Manitoba, Winnipeg, MB, CanadaNencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, PolandSerotonin (5-hydroxytryptamine; 5-HT) plays an important role in control of locomotion, partly through direct effects on motoneurons. Spinal cord complete transection (SCI) results in changes in 5-HT receptors on motoneurons that influence functional recovery. Activation of 5-HT2A and 5-HT7 receptors improves locomotor hindlimb movements in paraplegic rats. Here, we analyzed the mRNA of 5-HT2A and 5-HT7 receptors (encoded by Htr2a and Htr7 genes, resp.) in motoneurons innervating tibialis anterior (TA) and gastrocnemius lateralis (GM) hindlimb muscles and the tail extensor caudae medialis (ECM) muscle in intact as well as spinal rats. Moreover, the effect of intraspinal grafting of serotonergic neurons on Htr2a and Htr7 gene expression was examined to test the possibility that the graft origin 5-HT innervation in the spinal cord of paraplegic rats could reverse changes in gene expression induced by SCI. Our results indicate that SCI at the thoracic level leads to changes in Htr2a and Htr7 gene expression, whereas transplantation of embryonic serotonergic neurons modifies these changes in motoneurons innervating hindlimb muscles but not those innervating tail muscles. This suggests that the upregulation of genes critical for locomotor recovery, resulting in limb motoneuron plasticity, might account for the improved locomotion in grafted animals.http://dx.doi.org/10.1155/2018/4232706
spellingShingle Krzysztof Miazga
Hanna Fabczak
Ewa Joachimiak
Małgorzata Zawadzka
Łucja Krzemień-Ojak
Marek Bekisz
Anna Bejrowska
Larry M. Jordan
Urszula Sławińska
Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
Neural Plasticity
title Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
title_full Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
title_fullStr Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
title_full_unstemmed Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
title_short Intraspinal Grafting of Serotonergic Neurons Modifies Expression of Genes Important for Functional Recovery in Paraplegic Rats
title_sort intraspinal grafting of serotonergic neurons modifies expression of genes important for functional recovery in paraplegic rats
url http://dx.doi.org/10.1155/2018/4232706
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