Dubový Petr, Klusáková Ilona, Hradilová-Svíženská Ivana, Brázda Václav, Kohoutková Marcela, Joukal Marek
Department of Anatomy, Laboratory of Cellular and Molecular Neurobiology, Faculty of Medicine, Masaryk University, Brno, Czechia.
Front Cell Neurosci. 2019 Feb 4;13:11. doi: 10.3389/fncel.2019.00011. eCollection 2019.
The primary sensory neurons of dorsal root ganglia (DRG) are a very useful model to study the neuronal regenerative program that is a prerequisite for successful axon regeneration after peripheral nerve injury. Seven days after a unilateral sciatic nerve injury by compression or transection, we detected a bilateral increase in growth-associated protein-43 (GAP-43) and superior cervical ganglion-10 (SCG-10) mRNA and protein levels not only in DRG neurons of lumbar spinal cord segments (L4-L5) associated with injured nerve, but also in remote cervical segments (C6-C8). The increase in regeneration-associated proteins in the cervical DRG neurons was associated with the greater length of regenerated axons 1 day after ulnar nerve crush following prior sciatic nerve injury as compared to controls with only ulnar nerve crush. The increased axonal regeneration capacity of cervical DRG neurons after a prior conditioning sciatic nerve lesion was confirmed by neurite outgrowth assay of cultivated DRG neurons. Intrathecal injection of IL-6 or a JAK2 inhibitor (AG490) revealed a role for the IL-6 signaling pathway in activating the pro-regenerative state in remote DRG neurons. Our results suggest that the pro-regenerative state induced in the DRG neurons non-associated with the injured nerve reflects a systemic reaction of these neurons to unilateral sciatic nerve injury.
背根神经节（DRG）的初级感觉神经元是研究神经元再生程序的非常有用的模型，而神经元再生程序是周围神经损伤后轴突成功再生的先决条件。在单侧坐骨神经通过压迫或横断损伤7天后，我们不仅在与受伤神经相关的腰脊髓节段（L4-L5）的DRG神经元中，而且在远端颈节段（C6-C8）中检测到生长相关蛋白43（GAP-43）和颈上神经节10（SCG-10）的mRNA和蛋白水平双侧增加。与仅接受尺神经挤压的对照组相比，坐骨神经损伤后，尺神经挤压1天后，颈DRG神经元中再生相关蛋白的增加与再生轴突的长度增加有关。通过培养的DRG神经元的神经突生长试验证实了先前的坐骨神经损伤预处理后颈DRG神经元轴突再生能力的增强。鞘内注射IL-6或JAK2抑制剂（AG490）揭示了IL-6信号通路在激活远端DRG神经元的促再生状态中的作用。我们的结果表明，在与受伤神经不相关的DRG神经元中诱导的促再生状态反映了这些神经元对单侧坐骨神经损伤的全身反应。
