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 BE Shields,
Christopher B Shields,
Dale R Sengelaub,
Kathryn J Jones,
George M Smith,
Xiao-Ming Xu
Affiliations
Ying Wang
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States; Neural Tissue Engineering Research Institute, Mudanjiang College of Medicine, Mudanjiang, China
Wei Wu
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Xiangbing Wu
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Yan Sun
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States; Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Fudan University, Shanghai, China
Yi P Zhang
Norton Neuroscience Institute, Norton Healthcare, Louisville, United States
Ling-Xiao Deng
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Melissa Jane Walker
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Wenrui Qu
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States; Program in Medical Neuroscience, Paul and Carole Stark Neurosciences Research Institute, Indiana University School of Medicine, Indiana, United States
Nai-Kui Liu
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Qi Han
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Heqiao Dai
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States
Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, United States; Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, United States; Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, United States
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.
