Department of Cell Physiology, Ruhr University of Bochum, Universitätsstraße 150, 44780, Bochum, Germany.
Nat Commun. 2021 Jan 15;12(1):391. doi: 10.1038/s41467-020-20112-4.
Spinal cord injury (SCI) often causes severe and permanent disabilities due to the regenerative failure of severed axons. Here we report significant locomotor recovery of both hindlimbs after a complete spinal cord crush. This is achieved by the unilateral transduction of cortical motoneurons with an AAV expressing hyper-IL-6 (hIL-6), a potent designer cytokine stimulating JAK/STAT3 signaling and axon regeneration. We find collaterals of these AAV-transduced motoneurons projecting to serotonergic neurons in both sides of the raphe nuclei. Hence, the transduction of cortical neurons facilitates the axonal transport and release of hIL-6 at innervated neurons in the brain stem. Therefore, this transneuronal delivery of hIL-6 promotes the regeneration of corticospinal and raphespinal fibers after injury, with the latter being essential for hIL-6-induced functional recovery. Thus, transneuronal delivery enables regenerative stimulation of neurons in the deep brain stem that are otherwise challenging to access, yet highly relevant for functional recovery after SCI.
脊髓损伤（SCI）常因切断轴突的再生失败而导致严重且永久性的残疾。在此，我们报告了完全性脊髓横断后双侧后肢运动功能的显著恢复。这是通过单侧转导表达高活性白细胞介素 6（hIL-6）的腺相关病毒（AAV）实现的，hIL-6 是一种有效的设计细胞因子，可刺激 JAK/STAT3 信号通路和轴突再生。我们发现这些转导的运动神经元的侧支投射到中缝核双侧的 5-羟色胺能神经元。因此，皮质神经元的转导促进了 hIL-6 在脑干支配神经元中的轴突运输和释放。因此，hIL-6 的这种跨神经元传递促进了损伤后皮质脊髓和中缝脊髓纤维的再生，后者对于 hIL-6 诱导的功能恢复至关重要。因此，跨神经元传递能够刺激深部脑干中神经元的再生，否则这些神经元难以接触，但对于 SCI 后的功能恢复非常重要。
