Department of Spine Surgery, Wenzhou Medical University First Affiliated Hospital, Wenzhou, Zhejiang, China.
Department of Emergency Medicine, Wenzhou Medical University Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou, Zhejiang, China.
CNS Neurosci Ther. 2018 Dec;24(12):1185-1195. doi: 10.1111/cns.12856. Epub 2018 Apr 15.
Autophagy has been regarded as a promising therapeutic target for spinal cord injury (SCI). Erythropoietin (EPO) has been demonstrated to exhibit neuroprotective effects in the central nervous system (CNS); however, the molecular mechanisms of its protection against SCI remain unknown. This study aims to investigate whether the neuroprotective effects of EPO on SCI are mediated by autophagy via AMP-activated protein kinase (AMPK) signaling pathways.
Functional assessment and Nissl staining were used to investigate the effects of EPO on SCI. Expressions of proteins were detected by Western blot and immunohistochemistry.
Treatment with EPO significantly reduced the loss of motor neurons and improved the functional recovery following SCI. Erythropoietin significantly enhanced the SCI-induced autophagy through activating AMPK and inactivating mTOR signaling. The inhibitor of AMPK, compound C, could block the EPO-induced autophagy and beneficial action on SCI, whereas the activator of AMPK, metformin, could mimic the effects of EPO. In the in vitro studies, EPO enhanced the hypoxia-induced autophagy in an AMPK-dependent manner.
The AMPK-dependent induction of autophagy contributes to the neuroprotection of EPO on SCI.
自噬已被认为是脊髓损伤 (SCI) 的一种有前途的治疗靶点。促红细胞生成素 (EPO) 已被证明在中枢神经系统 (CNS) 中具有神经保护作用；然而，其对 SCI 的保护作用的分子机制尚不清楚。本研究旨在探讨 EPO 是否通过 AMP 激活蛋白激酶 (AMPK) 信号通路介导对 SCI 的神经保护作用。
通过功能评估和尼氏染色来研究 EPO 对 SCI 的影响。通过 Western blot 和免疫组化检测蛋白表达。
EPO 治疗可显著减少运动神经元的丢失，并改善 SCI 后的功能恢复。EPO 通过激活 AMPK 并抑制 mTOR 信号来显著增强 SCI 诱导的自噬。AMPK 的抑制剂，化合物 C，可以阻断 EPO 诱导的自噬和对 SCI 的有益作用，而 AMPK 的激活剂，二甲双胍，可以模拟 EPO 的作用。在体外研究中，EPO 以 AMPK 依赖的方式增强缺氧诱导的自噬。
AMPK 依赖性自噬的诱导有助于 EPO 对 SCI 的神经保护作用。
