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AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury

DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively prom...

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Autores principales: Li, Wen-Yuan, Wang, Ying, Zhai, Feng-Guo, Sun, Ping, Cheng, Yong-Xia, Deng, Ling-Xiao, Wang, Zhen-Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572611/
https://www.ncbi.nlm.nih.gov/pubmed/28884027
http://dx.doi.org/10.1155/2017/1621629
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author Li, Wen-Yuan
Wang, Ying
Zhai, Feng-Guo
Sun, Ping
Cheng, Yong-Xia
Deng, Ling-Xiao
Wang, Zhen-Yu
author_facet Li, Wen-Yuan
Wang, Ying
Zhai, Feng-Guo
Sun, Ping
Cheng, Yong-Xia
Deng, Ling-Xiao
Wang, Zhen-Yu
author_sort Li, Wen-Yuan
collection PubMed
description DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury.
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spelling pubmed-55726112017-09-07 AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury Li, Wen-Yuan Wang, Ying Zhai, Feng-Guo Sun, Ping Cheng, Yong-Xia Deng, Ling-Xiao Wang, Zhen-Yu Neural Plast Research Article DPSN axons mediate and maintain a variety of normal spinal functions. Unsurprisingly, DPSN tracts have been shown to mediate functional recovery following SCI. KLF7 could contribute to CST axon plasticity after spinal cord injury. In the present study, we assessed whether KLF7 could effectively promote DPSN axon regeneration and synapse formation following SCI. An AAV-KLF7 construct was used to overexpress KLF7. In vitro, KLF7 and target proteins were successfully elevated and axonal outgrowth was enhanced. In vivo, young adult C57BL/6 mice received a T10 contusion followed by an AAV-KLF7 injection at the T7–9 levels above the lesion. Five weeks later, overexpression of KLF7 was expressed in DPSN. KLF7 and KLF7 target genes (NGF, TrkA, GAP43, and P0) were detectably increased in the injured spinal cord. Myelin sparring at the lesion site, DPSN axonal regeneration and synapse formation, muscle weight, motor endplate morphology, and functional parameters were all additionally improved by KLF7 treatment. Our findings suggest that KLF7 promotes DPSN axonal plasticity and the formation of synapses with motor neurons at the caudal spinal cord, leading to improved functional recovery and further supporting the potential of AAV-KLF7 as a therapeutic agent for spinal cord injury. Hindawi 2017 2017-08-13 /pmc/articles/PMC5572611/ /pubmed/28884027 http://dx.doi.org/10.1155/2017/1621629 Text en Copyright © 2017 Wen-Yuan Li et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Li, Wen-Yuan
Wang, Ying
Zhai, Feng-Guo
Sun, Ping
Cheng, Yong-Xia
Deng, Ling-Xiao
Wang, Zhen-Yu
AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title_full AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title_fullStr AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title_full_unstemmed AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title_short AAV-KLF7 Promotes Descending Propriospinal Neuron Axonal Plasticity after Spinal Cord Injury
title_sort aav-klf7 promotes descending propriospinal neuron axonal plasticity after spinal cord injury
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5572611/
https://www.ncbi.nlm.nih.gov/pubmed/28884027
http://dx.doi.org/10.1155/2017/1621629
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