Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice
Descending motor circuitry required for NT-3 mediated locomotor recovery after spinal cord injury in mice
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DOI：
10.1038/s41467-019-13854-3
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发表时间：
2019-12-20
影响因子：
16.6
通讯作者：
Xu, Xiao-Ming
中科院分区：
文献类型：
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作者：
Han, Qi;Ordaz, Josue D.;Xu, Xiao-Ming
腰椎神经回路介导的运动功能受下行脊髓通路的调节。脊髓损伤(SCI)中断下行投射，使腰椎运动神经元(MNS)失神经。我们以前曾报道，将神经营养素-3(NT-3)逆行转运到腰椎MNS可以减轻脊髓损伤诱导的腰椎MN树突萎缩，并使胸部吻侧挫伤后的功能恢复。在这里，我们从功能上剖析了下行神经通路在小鼠T9挫伤脊髓损伤后NT-3介导的恢复中所起的作用。我们发现，脊髓损伤后产生腿部运动需要对腰椎MN的残存投影。接下来，我们证明备用的固有脊髓下行通路，而不是其他通路(包括皮质脊髓、红核脊髓、5-羟色胺能和多巴胺能通路)，是NT-3促进恢复的原因。最后，我们证明NT-3在T9挫伤后通过促进树突状细胞的再生而不是阻止树突萎缩来诱导固有的脊髓-MN回路重组。
Locomotor function, mediated by lumbar neural circuitry, is modulated by descending spinal pathways. Spinal cord injury (SCI) interrupts descending projections and denervates lumbar motor neurons (MNs). We previously reported that retrogradely transported neurotrophin-3 (NT-3) to lumbar MNs attenuated SCI-induced lumbar MN dendritic atrophy and enabled functional recovery after a rostral thoracic contusion. Here we functionally dissected the role of descending neural pathways in response to NT-3-mediated recovery after a T9 contusive SCI in mice. We find that residual projections to lumbar MNs are required to produce leg movements after SCI. Next, we show that the spared descending propriospinal pathway, rather than other pathways (including the corticospinal, rubrospinal, serotonergic, and dopaminergic pathways), accounts for NT-3-enhanced recovery. Lastly, we show that NT-3 induced propriospino-MN circuit reorganization after the T9 contusion via promotion of dendritic regrowth rather than prevention of dendritic atrophy.