In strong contrast to limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of almost complete recovery following injury. Understanding the mechanism underlying neural repair and functional recovery in zebrafish may lead to innovative therapies for human spinal cord injury (SCI). Since neuropeptide Y (NPY) plays a protective role in the pathogenesis of several neurological diseases, in the present study, we evaluated the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish following SCI. Real-time quantitative PCR (qRT-PCR), in situ hybridization and immunostaining for NPY revealed decreased NPY expression at 12 hours (h), 6 and 21 days (d) after SCI. Double-immunostaining for NPY and islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. Morpholino (MO) treatment for suppressing the expression of NPY inhibited supraspinal axon regrowth and locomotor recovery, in which double-staining for proliferating cell nuclear antigen (PCNA) and islet-1 showed a reduction in motoneuron proliferation. Similarly, a downregulated mRNA level of Y1 receptor of NPY (NPY1R) was also detected at 12 h, 6 and 21 d after injury. Immunostaining for NPY and in situ hybridization for NPY1R revealed that NPY1R was co-localized with NPY. Collectively, the results suggest that NPY expression in motoneurons promotes descending axon regeneration and locomotor recovery in adult zebrafish after SCI, possibly by regulating motoneuron proliferation through activation of NPY1R.

与哺乳动物中枢神经系统内的有限修复形成鲜明对比的是，成年斑马鱼的脊髓在受伤后几乎能够完全恢复。了解斑马鱼神经修复和功能恢复的潜在机制可能会导致人类脊髓损伤 (SCI) 的创新疗法。由于神经肽 Y (NPY) 在几种神经系统疾病的发病机制中起保护作用，因此在本研究中，我们评估了 NPY 对 SCI 后成年斑马鱼的神经元修复和随后运动功能恢复的影响。实时定量 PCR (qRT-PCR)、NPY 的原位杂交和免疫染色显示，在 SCI 后 12 小时 (h)、6 天和 21 天 (d) NPY 表达降低。NPY 和 islet-1（一种运动神经元标记物）的双重免疫染色，表明 NPY 在脊髓运动神经元中表达。用于抑制 NPY 表达的 Morpholino (MO) 治疗抑制了脊髓上轴突再生和运动恢复，其中增殖细胞核抗原 (PCNA) 和胰岛 1 的双染色显示运动神经元增殖减少。类似地，在损伤后 12 小时、6 和 21 天也检测到 NPY 的 Y1 受体（NPY1R）的 mRNA 水平下调。NPY 的免疫染色和NPY1R 的原位杂交显示 NPY1R 与 NPY 共定位。总的来说，结果表明运动神经元中的 NPY 表达促进 SCI 后成年斑马鱼的下行轴突再生和运动恢复，可能是通过激活 NPY1R 调节运动神经元增殖。