Spinal cord injury (SCI) causes severe neurological dysfunction such as motor deficits and sensory impairments caused by the disruption of neuronal networks. Injured neurons in the central nervous system spontaneously regenerate their neuronal network, resulting in promoting functional recovery. However, the regenerative capacity in the adult central nervous system is limited, therefore, understanding the mechanism that promotes regeneration of the neuronal network is required to establish a strategy for restoring motor function after SCI.
In this study, we explored the factor that promotes neurite elongation using in vitro siRNA-screening and found that Synaptotagmin 4 (Syt4) has a potential to promote neurite elongation. We detected that Syt4 is mainly expressed in neurons in the brain compared with other organs. To ask the function of Syt4 in vivo, we injected adeno-associated virus 9 (AAV9) encoding shRNA against Syt4 into the motor cortex and found that suppression of Syt4 prevented regeneration of neuronal network and functional recovery in the mice with SCI. These results indicate that Syt4 expressing in neurons sustains the spontaneous regeneration of the neuronal network in the adult central nervous system.