Spinal Cord and Brain Injury Research Group, Stark Neurosciences Research Institute, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Department of Neurological Surgery, Indiana University School of Medicine, Indianapolis, IN, 46202, USA.
Nat Commun. 2019 Dec 20;10(1):5815. doi: 10.1038/s41467-019-13854-3.
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.
运动功能由腰骶神经回路介导，受下行脊髓通路调节。脊髓损伤（SCI）会中断下行投射并使腰骶运动神经元（MNs）去神经支配。我们之前的研究报告称，逆行转运的神经营养因子-3（NT-3）向腰骶 MNs 的运输可减轻 SCI 诱导的腰骶 MN 树突萎缩，并在 T9 挫伤后实现功能恢复。在这里，我们在小鼠 T9 挫伤性 SCI 后，从功能上解析了 NT-3 介导的恢复中下行神经通路的作用。我们发现，残留的腰骶 MN 投射对于 SCI 后腿部运动是必需的。接下来，我们表明，未受损的脊髓固有通路，而不是其他通路（包括皮质脊髓、红核脊髓、血清素能和多巴胺能通路），是 NT-3 增强恢复的原因。最后，我们表明，NT-3 通过促进树突再生而不是防止树突萎缩，在 T9 挫伤后诱导固有脊髓-MN 回路重组。
