Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery

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 2 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.
Source: eLife - Category: Biomedical Science Tags: Neuroscience Source Type: research

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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research
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Source: Tissue and Cell - Category: Cytology Authors: Tags: Tissue Cell Source Type: research
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ConclusionAdv ‐HIF‐1α improves functional recovery in rats with SCI, and the underlying mechanism may be related to the mobilization of BMSCs to the injured area and higher expression levels of NT‐3 and BDNF.
Source: The Journal of Gene Medicine - Category: Genetics & Stem Cells Authors: Tags: RESEARCH ARTICLE Source Type: research
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Source: Life Sciences - Category: Biology Source Type: research
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Source: Behavioural Neurology - Category: Neurology Authors: Tags: Behav Neurol Source Type: research
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Source: Innovations in Clinical Neuroscience - Category: Neuroscience Authors: Tags: Commentary Current Issue Source Type: research
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Source: NeuroReport - Category: Neurology Tags: Clinical Neuroscience Source Type: research
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Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research
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