TY - JOUR
T1 - Matrine promotes neural circuit remodeling to regulate motor function in a mouse model of chronic spinal cord injury
AU - Tanabe, Norio
AU - Kuboyama, Tomoharu
AU - Tohda, Chihiro
N1 - Publisher Copyright:
© 2019 Wolters Kluwer Medknow Publications. All rights reserved.
PY - 2019/7/9
Y1 - 2019/7/9
N2 - 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.
AB - 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.
KW - Axonal growth
KW - Basso mouse scale
KW - Body support score
KW - Chronic spinal cord injury
KW - Hindlimb locomotor
KW - Immunohistochemistry
KW - Matrine
KW - Presynapse
KW - Sophora flavescens
KW - Synaptogenesis
UR - http://www.scopus.com/inward/record.url?scp=85072069730&partnerID=8YFLogxK
U2 - 10.4103/1673-5374.259625
DO - 10.4103/1673-5374.259625
M3 - 学術論文
AN - SCOPUS:85072069730
SN - 1673-5374
VL - 14
SP - 1961
EP - 1967
JO - Neural Regeneration Research
JF - Neural Regeneration Research
IS - 11
ER -