Department of Orthopaedic Surgery, Tohoku University School of Medicine, Sendai, Japan.
J Neurotrauma. 2012 Mar 20;29(5):946-56. doi: 10.1089/neu.2011.1919. Epub 2011 Sep 21.
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that negatively regulates autophagy. Rapamycin, an inhibitor of mTOR signaling, can promote autophagy and exert neuroprotective effects in several diseases of the central nervous system (CNS). In the present study, we examined whether rapamycin treatment promotes autophagy and reduces neural tissue damage and locomotor impairment after spinal cord injury (SCI) in mice. Our results demonstrated that the administration of rapamycin significantly decreased the phosphorylation of the p70S6K protein and led to higher expression levels of LC3 and Beclin 1 in the injured spinal cord. In addition, neuronal loss and cell death in the injured spinal cord were significantly reduced in the rapamycin-treated mice compared to the vehicle-treated mice. Furthermore, the rapamycin-treated mice showed significantly higher locomotor function in Basso Mouse Scale (BMS) scores than did the vehicle-treated mice. These results indicate that rapamycin promoted autophagy by inhibiting the mTOR signaling pathway, and reduced neural tissue damage and locomotor impairment after SCI. The administration of rapamycin produced a neuroprotective function at the lesion site following SCI. Rapamycin treatment may represent a novel therapeutic strategy after SCI.
哺乳动物雷帕霉素靶蛋白（mTOR）是一种丝氨酸/苏氨酸激酶，可负向调节自噬。雷帕霉素是 mTOR 信号通路的抑制剂，可在中枢神经系统（CNS）的几种疾病中促进自噬并发挥神经保护作用。在本研究中，我们研究了雷帕霉素治疗是否能促进自噬，减少小鼠脊髓损伤（SCI）后的神经组织损伤和运动功能障碍。我们的结果表明，雷帕霉素的给药显著降低了 p70S6K 蛋白的磷酸化水平，并导致损伤脊髓中 LC3 和 Beclin 1 的表达水平升高。与载体处理的小鼠相比，雷帕霉素处理的小鼠损伤脊髓中的神经元丢失和细胞死亡明显减少。此外，雷帕霉素处理的小鼠在 Basso Mouse Scale（BMS）评分中的运动功能明显优于载体处理的小鼠。这些结果表明，雷帕霉素通过抑制 mTOR 信号通路促进自噬，并减少 SCI 后的神经组织损伤和运动功能障碍。雷帕霉素在 SCI 后的损伤部位具有神经保护作用。雷帕霉素治疗可能是 SCI 后的一种新的治疗策略。
