Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury

In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness...

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Main Authors: Norio Tanabe, Tomoharu Kuboyama, Chihiro Tohda
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2019-01-01
Series:Neural Regeneration Research
Subjects:
Online Access:http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1961;epage=1967;aulast=Tanabe
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author Norio Tanabe
Tomoharu Kuboyama
Chihiro Tohda
author_facet Norio Tanabe
Tomoharu Kuboyama
Chihiro Tohda
author_sort Norio Tanabe
collection DOAJ
description In chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine (100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous matrine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama (approval No. A2013INM-1 and A2016INM-3) on May 7, 2013 and May 17, 2016, respectively.
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spelling doaj.art-ecd8f3c5d8da46f4a5524dab5a6c4a2e2022-12-22T00:07:30ZengWolters Kluwer Medknow PublicationsNeural Regeneration Research1673-53742019-01-0114111961196710.4103/1673-5374.259625Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injuryNorio TanabeTomoharu KuboyamaChihiro TohdaIn chronic phase of spinal cord injury, functional recovery is more untreatable compared with early intervention in acute phase of spinal cord injury. In the last decade, several combination therapies successfully improved motor dysfunction in chronic spinal cord injury. However, their effectiveness is not sufficient. We previously found a new effective compound for spinal cord injury, matrine, which induced axonal growth and functional recovery in acute spinal cord injury mice via direct activation of extracellular heat shock protein 90. Although our previous study clarified that matrine was an activator of extracellular heat shock protein 90, the potential of matrine for spinal cord injury in chronic phase has not been sufficiently evaluated. Thus, this study aimed to investigate whether matrine ameliorates chronic spinal cord injury in mice. Once daily intragastric administration of matrine (100 μmol/kg per day) to spinal cord injury mice were starte at 28 days after injury, and continued for 154 days. Continuous matrine treatment improved hindlimb motor function in chronic spinal cord injury mice. In injured spinal cords of the matrine-treated mice, the density of neurofilament-H-positive axons was increased. Moreover, matrine treatment increased the density of bassoon-positive presynapses in contact with choline acetyltransferase-positive motor neurons in the lumbar spinal cord. These findings suggest that matrine promotes remodeling and reconnection of neural circuits to regulate hindlimb movement. All protocols were approved by the Committee for Animal Care and Use of the Sugitani Campus of the University of Toyama (approval No. A2013INM-1 and A2016INM-3) on May 7, 2013 and May 17, 2016, respectively.http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1961;epage=1967;aulast=Tanabematrine; chronic spinal cord injury; axonal growth; synaptogenesis; hindlimb locomotor; presynapse; immunohistochemistry; Basso Mouse Scale; Body Support Score; Sophora flavescens
spellingShingle Norio Tanabe
Tomoharu Kuboyama
Chihiro Tohda
Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
Neural Regeneration Research
matrine; chronic spinal cord injury; axonal growth; synaptogenesis; hindlimb locomotor; presynapse; immunohistochemistry; Basso Mouse Scale; Body Support Score; Sophora flavescens
title Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
title_full Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
title_fullStr Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
title_full_unstemmed Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
title_short Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
title_sort matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
topic matrine; chronic spinal cord injury; axonal growth; synaptogenesis; hindlimb locomotor; presynapse; immunohistochemistry; Basso Mouse Scale; Body Support Score; Sophora flavescens
url http://www.nrronline.org/article.asp?issn=1673-5374;year=2019;volume=14;issue=11;spage=1961;epage=1967;aulast=Tanabe
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AT tomoharukuboyama matrinepromotesneuralcircuitremodelingtoregulatemotorfunctioninamousemodelofchronicspinalcordinjury
AT chihirotohda matrinepromotesneuralcircuitremodelingtoregulatemotorfunctioninamousemodelofchronicspinalcordinjury