Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery.
Remodeling of lumbar motor circuitry remote to a thoracic spinal cord injury promotes locomotor recovery.
复制标题
重塑远离胸部脊髓损伤的腰部运动回路可促进运动恢复。
作者：
Wang Y;Wu W;Wu X;Sun Y;Zhang YP;Deng LX;Walker MJ;Qu W;Chen C;Liu NK;Han Q;Dai H;Shields LB;Shields CB;Sengelaub DR;Jones KJ;Smith GM;Xu XM
神经营养因子信号在神经回路特异性调节中起重要作用。在这里，我们调查是否有针对性的交付神经营养素-3（NT-3）的腰运动神经元（MN）尾侧胸（T10）挫伤性脊髓损伤（SCI）可以调节树突状图案和突触形成的腰MN。在体外培养的脊髓神经元中，过表达NT-3的腺相关病毒血清型2（AAV-NT-3）诱导NT-3表达和轴突生长。在体内，将AAV-NT-3靶向递送到短暂脱髓鞘的成年小鼠坐骨神经中导致NT-3逆行运输到腰椎MN，显著减弱SCI诱导的腰椎MN树突状萎缩。NT-3增强了腰椎MN上下行的多巴胺能、多巴胺能和本体脊髓轴突的发芽和突触形成，与改善的行为恢复平行。因此，逆行运输NT-3刺激腰椎神经回路和突触连接的重建远程胸部SCI，支持作为SCI的潜在治疗策略的NT-3逆行运输的作用。
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.