Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Sep 12, 2018
- Source ID
- 10.7554/elife.39016
Entities
People
- Chen Chen
- Christopher B. Shields
- Dale R Sengelaub
- George M. Smith
- Heqiao Dai
- Kathryn J Jones
- Ling-xiao Deng
- Lisa B. E. Shields
- Melissa Jane Walker
- Nai-kui Liu
- Qi Han
- Wei Wu
- Wenrui Qu
- Xiangbing Wu
- Xiao-Ming Xu
- Yan Sun
- Yi P Zhang
- Ying Wang
Organizations
- Craig H Neilsen Foundation
- Fudan University
- Indiana State Department of Health
- Indiana University
- National Institutes of Health
- National Natural Science Foundation of China
- Temple University
- United States Department of Defense
- United States Department of Veterans Affairs