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, Nai Kui Liu, Qi Han, Heqiao Dai, Lisa B.E. Shields, Christopher B. Shields, Dale R. Sengelaub, Kathryn J. Jones, George M. Smith, Xiao Ming Xu

Research output: Contribution to journalArticle

12 Scopus citations

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)
Article numbere39016
JournaleLife
Volume7
DOIs
StatePublished - Sep 2018

ASJC Scopus subject areas

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

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