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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 Liu, Nai-Kui
Wang, Ying
Wu, Wei
Wu, Xiangbing
Sun, Yan
Zhang, Yi P.
Deng, Ling-Xiao
Walker, Melissa Jane
Qu, Wenrui
Liu, Nai-Kui
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Journal article
Date
2018-10-03
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Neural Sciences
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https://doi.org/10.7554/elife.39016
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.
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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 BE Shields, Christopher B Shields, Dale R Sengelaub, Kathryn J Jones, George M Smith, Xiao-Ming Xu (2018) Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery eLife 7:e39016. https://doi.org/10.7554/eLife.39016
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eLife Sciences Publications
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eLife, Vol. 7
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