Regulation of autophagy by AMP-activated protein kinase/ sirtuin ۱ pathway reduces spinal cord neurons damage

Objective(s): AMP-activated protein kinase/sirtuin ۱ (AMPK/SIRT۱) signaling pathway has been proved to be involved in the regulation of autophagy in various models. The aim of this study was to evaluate the effect of AMPK/SIRT۱ pathway on autophagy after spinal cord injury (SCI). Materials and Methods:The SCI model was established in rats in vivo and the primary spinal cord neurons were subjected to mechanical injury (MI) in vitro. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst ۳۳۳۴۲ staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation of AMPK/SIRT۱ pathway was determined by Western blot and immunohistochemical staining. Results: We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC۳II/LC۳I and level of p۶۲ were first increased significantly and then decreased after the trauma in vivo and in vitro, indicating the defect in autophagy. The levels of p-AMPK and SIRT۱ were increased obviously after the trauma in vivo and in vitro. Further activation of the AMPK/SIRT۱ pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT۱ pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p۶۲ in spinal cord neurons at ۲۴ hr after MI. Conclusion: Our results demonstrate that regulation of autophagy by AMPK/SIRT۱ pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.

Keywords:

AMPK/SIRT۱ pathway , Autophagy flux , p۶۲ , Resveratrol , Spinal cord injury