Apelin regulates mitochondrial dynamics by inhibiting Mst1-JNK-Drp1 signaling pathway to reduce neuronal apoptosis after spinal cord injury

In the secondary injury stage of spinal cord injury, mitochondrial dysfunction leads to decreased ATP production, increased ROS production, and activation of the mitochondria-mediated apoptosis signaling pathway. This ultimately intensifies neuronal death and promotes the progression of the injury. Apelin, a peptide produced by the APLN gene, has demonstrated promise in the treatment of spinal cord injuries. The aim of this study was to investigate how Apelin protects neurons after spinal cord injury by influencing the mitochondrial dynamics. The results showed that Apelin has the ability to reduce mitochondrial division in PC12 cells, enhance the mitochondrial membrane potential, improve antioxidant capacity, facilitate the clearance of excess ROS, and ultimately decrease apoptosis. Moreover, Apelin is overexpressed in neurons in the damaged part of the spinal cord, contributing to reduce mitochondrial division, improved antioxidant capacity, increased ATP production, decreased apoptosis, promoted spinal cord morphological repair, maintained the number of nissl bodies, and enhanced signal transduction in the descending spinal cord pathway. Apelin exerts its protective effect by inhibiting the Mst1-JNK-Drp1 signaling pathway. In summary, our study further improved the effect of Apelin in the treatment of spinal cord injury, revealed the mechanism of Apelin in protecting damaged neurons after spinal cord injury by maintaining mitochondrial homeostasis, and provided a new therapeutic mechanism for Apelin in spinal cord injury.