Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

Ying Wang, Wei Wu, Xiangbing Wu, Yan Sun, Yi P. Zhang, Ling Xiao Deng, Melissa Jane Walker, Wenrui Qu, Chen Chen, Naikui Liu, Qi Han, Heqiao Dai, Lisa Be Shields, Christopher B. Shields, Dale R. Sengelaub, Kathryn Jones, George M. Smith, Xiao-Ming Xu

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Retrogradely-transported neurotrophin signaling plays an important role in regulating neural circuit specificity. Here we investigated whether targeted delivery of neurotrophin-3 (NT-3) to lumbar motoneurons (MNs) caudal to a thoracic (T10) contusive spinal cord injury (SCI) could modulate dendritic patterning and synapse formation of the lumbar MNs. In vitro, Adeno-associated virus serotype two overexpressing NT-3 (AAV-NT-3) induced NT-3 expression and neurite outgrowth in cultured spinal cord neurons. In vivo, targeted delivery of AAV-NT-3 into transiently demyelinated adult mouse sciatic nerves led to the retrograde transportation of NT-3 to the lumbar MNs, significantly attenuating SCI-induced lumbar MN dendritic atrophy. NT-3 enhanced sprouting and synaptic formation of descending serotonergic, dopaminergic, and propriospinal axons on lumbar MNs, parallel to improved behavioral recovery. Thus, retrogradely transported NT-3 stimulated remodeling of lumbar neural circuitry and synaptic connectivity remote to a thoracic SCI, supporting a role for retrograde transport of NT-3 as a potential therapeutic strategy for SCI.

Original languageEnglish (US)
JournaleLife
Volume7
DOIs
StatePublished - Sep 12 2018

Fingerprint

Neurotrophin 3
Thoracic Injuries
Spinal Cord Injuries
Recovery
Motor Neurons
Dependovirus
Nerve Growth Factors
Sciatic Nerve
Viruses
Synapses
Neurons
Atrophy
Axons
Spinal Cord
Thorax

Keywords

  • dendritic morphology
  • lumbar motoneuron
  • mouse
  • neuroscience
  • NT-3
  • plasticity
  • retrograde transport
  • spinal cord injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

Cite this

Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery. / Wang, Ying; Wu, Wei; Wu, Xiangbing; Sun, Yan; Zhang, Yi P.; Deng, Ling Xiao; Walker, Melissa Jane; Qu, Wenrui; Chen, Chen; Liu, Naikui; Han, Qi; Dai, Heqiao; Shields, Lisa Be; Shields, Christopher B.; Sengelaub, Dale R.; Jones, Kathryn; Smith, George M.; Xu, Xiao-Ming.

In: eLife, Vol. 7, 12.09.2018.

Research output: Contribution to journalArticle

Wang, Y, Wu, W, Wu, X, Sun, Y, Zhang, YP, Deng, LX, Walker, MJ, Qu, W, Chen, C, Liu, N, Han, Q, Dai, H, Shields, LB, Shields, CB, Sengelaub, DR, Jones, K, Smith, GM & Xu, X-M 2018, 'Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery', eLife, vol. 7. https://doi.org/10.7554/eLife.39016
Wang, Ying ; Wu, Wei ; Wu, Xiangbing ; Sun, Yan ; Zhang, Yi P. ; Deng, Ling Xiao ; Walker, Melissa Jane ; Qu, Wenrui ; Chen, Chen ; Liu, Naikui ; Han, Qi ; Dai, Heqiao ; Shields, Lisa Be ; Shields, Christopher B. ; Sengelaub, Dale R. ; Jones, Kathryn ; Smith, George M. ; Xu, Xiao-Ming. / Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery. In: eLife. 2018 ; Vol. 7.
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