Regulation of autophagy by AMP-activated protein kinase/ sirtuin 1 pathway reduces spinal cord neurons damage

Abstract

<strong><em>Objective(s)</em></strong>: AMP-activated protein kinase/sirtuin 1 (AMPK/SIRT1) 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/SIRT1 pathway on autophagy after spinal cord injury (SCI).<br /> <strong><em>Materials and Methods:</em></strong>The SCI model was established in rats<em> in vivo </em>and the primary spinal cord neurons were subjected to mechanical injury (MI) <em>in vitro</em>. The apoptosis in spinal cord tissue and neurons was assessed by TUNEL staining and Hoechst 33342 staining, respectively. The autophagy-related proteins levels were detected by Western blot. The activation <strong>of</strong> AMPK/SIRT1 pathway was determined by Western blot and immunohistochemical staining.<br /> <strong><em>Results:</em></strong> We found that the apoptosis of spinal cord tissue and cell damage of spinal cord neurons was obvious after the trauma. The ratio of LC3II/LC3I and level of p62 were first increased significantly and then decreased after the trauma <em>in vivo </em>and <em>in vitro</em>, indicating the defect in autophagy. The levels of p-AMPK and SIRT1 were increased obviously after the trauma <em>in vivo </em>and<em> in vitro</em>. Further activation of the AMPK/SIRT1 pathway by pretreatment with resveratrol, a confirmed activator of the AMPK/SIRT1 pathway, alleviated the cell damage and promoted the autophagy flux via downregulation of p62 in spinal cord neurons at 24 hr after MI.<br /> <strong><em>Conclusion:</em></strong> Our results demonstrate that regulation of autophagy by AMPK/SIRT1 pathway can restrain spinal cord neurons damage, which may be a potential intervention of SCI.