Therapeutic effects of exendin‐4 on spinal cord injury via restoring autophagy function and decreasing necroptosis in neuron

Abstract

AbstractAimsNecroptosis is one of programmed death that may aggravate spinal cord injury (SCI). We aimed to investigate the effect and mechanism of exendin‐4 (EX‐4) on the recovery of motor function and necroptosis after SCI.MethodsThe SD rats with left hemisection in the T10 spinal cord as SCI model were used. The behavior tests were measured within 4 weeks. The effects of EX‐4 on necroptosis‐associated proteins and autophagy flux were explored. In addition, the SHSY5Y cell model was introduced to explore the direct effect of EX‐4 on neurons. The effect of lysosome was explored using mTOR activator and AO staining.ResultsEX‐4 could improve motor function and limb strength, promote the recovery of autophagy flux, and accelerate the degradation of necroptosis‐related protein at 3 d after injury in rats. EX‐4 reduced lysosome membrane permeability, promoted the recovery of lysosome function and autophagy flux, and accelerated the degradation of necroptosis‐related proteins by inhibiting the phosphorylation level of mTOR in the SHSY5Y cell model.ConclusionOur results demonstrated that EX‐4 may improve motor function after SCI via inhibiting mTOR phosphorylation level and accelerating the degradation of necroptosis‐related proteins in neurons. Our findings may provide new therapeutic targets for clinical treatment after SCI.