Rapamycin Promotes Autophagy and Reduces Neural Tissue Damage and Locomotor Impairment after Spinal Cord Injury in Mice
Rapamycin Promotes Autophagy and Reduces Neural Tissue Damage and Locomotor Impairment after Spinal Cord Injury in Mice
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DOI：
10.1089/neu.2011.1919
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发表时间：
2012-03-01
影响因子：
4.2
通讯作者：
Itoi, Eiji
中科院分区：
文献类型：
--
作者：
Sekiguchi, Akira;Kanno, Haruo;Itoi, Eiji
哺乳动物雷帕霉素靶蛋白（mTOR）是一种负调节自噬的丝氨酸/苏氨酸激酶。雷帕霉素是mTOR信号传导的抑制剂，可促进自噬并在多种中枢神经系统（CNS）疾病中发挥神经保护作用。在本研究中，我们研究了雷帕霉素治疗是否促进自噬，减少脊髓损伤（SCI）后小鼠神经组织损伤和运动障碍。我们的研究结果表明，雷帕霉素的管理显着降低了p70 S6 K蛋白的磷酸化，并导致更高的表达水平的LC 3和Beclin 1在损伤的脊髓。此外，与溶剂处理的小鼠相比，雷帕霉素处理的小鼠中受损脊髓中的神经元损失和细胞死亡显著减少。此外，雷帕霉素处理的小鼠在Basso小鼠量表（BMS）评分中显示出比载体处理的小鼠显著更高的运动功能。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障碍。给予雷帕霉素在SCI后的损伤部位产生神经保护功能。雷帕霉素治疗可能是SCI后的一种新的治疗策略。
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.