Distinctive Alteration of Neuropeptide Y Expression Responsible for Neuro-Proliferation Following Zebrafish Spinal Cord Injury

Abstract In strong contrast to the limited repair within the mammalian central nervous system, the spinal cord of adult zebrafish is capable of regeneration following injury. Understanding the mechanism underlying neural regeneration and functional recovery in spinal cord-injured zebrafish may lead to effective 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, the effects of NPY on neuronal repair and subsequent recovery of motor function in adult zebrafish post-SCI were evaluated. Real-time quantitative PCR (qRT-PCR), in situ hybridization (ISH) and immunostaining of NPY revealed decreased NPY expression at 12 hours (h), 6 days (d) and 21 d after SCI. Double-immunostaining for NPY and Islet-1, a motoneuron marker, showed that NPY was expressed in spinal cord motoneurons. NPY morpholino (MO) treatment resulted in suppressed locomotor recovery and axon regrowth. PCNA and Islet-1 double-staining showed suppressed motoneuron proliferation in NPY-MO zebrafish. Similar to NYP, the mRNA level for NPY1R was also expressed within motoneurons and downregulated at 12 h and 21 d after SCI. Collectively, these data suggest that NPY expression in motoneurons promotes locomotor recovery and axon regrowth in adult zebrafish, possibly by regulating motoneuron proliferation through the activation of NPY1R.