TY - JOUR TI - Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery AU - Wang, Ying AU - Wu, Wei AU - Wu, Xiangbing AU - Sun, Yan AU - Zhang, Yi P AU - Deng, Ling-Xiao AU - Walker, Melissa Jane AU - Qu, Wenrui AU - Chen, Chen AU - Liu, Nai-Kui AU - Han, Qi AU - Dai, Heqiao AU - Shields, Lisa BE AU - Shields, Christopher B AU - Sengelaub, Dale R AU - Jones, Kathryn J AU - Smith, George M AU - Xu, Xiao-Ming VL - 7 PY - 2018 DA - 2018/09/12 SP - e39016 C1 - eLife 2018;7:e39016 DO - 10.7554/eLife.39016 UR - https://doi.org/10.7554/eLife.39016 AB - 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. KW - NT-3 KW - retrograde transport KW - lumbar motoneuron KW - dendritic morphology KW - plasticity KW - spinal cord injury JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -