Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats
Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats
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DOI：
10.1007/s12264-016-0017-x
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发表时间：
2016-04-01
影响因子：
5.6
通讯作者：
Teng, Hong-Lin
中科院分区：
文献类型：
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作者：
Lin, Chao-Wei;Chen, Bi;Teng, Hong-Lin
17 β-雌二醇（E2）已被证明在不同的中枢神经系统疾病中具有神经保护作用。雌激素在脊髓损伤（SCI）中的神经保护机制尚不清楚。以往的研究表明，自噬在神经损伤过程中起着至关重要的作用。在这项研究中，我们表明，E2治疗促进了SCI大鼠运动功能的恢复，减少了运动神经元的丢失。Real-time PCR和western blot分析表明，E2的保护作用与抑制LC 3 Ⅱ和beclin-1的表达有关。免疫组化结果进一步证实，在运动神经元LC 3的免疫反应性下调时，E2。体外研究表明，在PC 12细胞模型中，E2预处理降低了雷帕霉素（自噬增敏剂）诱导的自噬活性并增加了存活率。这些结果表明，E2对SCI的神经保护作用部分与抑制过度的自噬有关。
17 beta-estradiol (E2) has been shown to have neuroprotective effects in different central nervous system diseases. The mechanisms underlying estrogen neuroprotection in spinal cord injury (SCI) remain unclear. Previous studies have shown that autophagy plays a crucial role in the course of nerve injury. In this study, we showed that E2 treatment improved the restoration of locomotor function and decreased the loss of motor neurons in SCI rats. Real-time PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3II and beclin-1 expression. Immunohistochemical study further confirmed that the immunoreactivity of LC3 in the motor neurons was down-regulated when treated with E2. In vitro studies demonstrated similar results that E2 pretreatment decreased the autophagic activity induced by rapamycin (autophagy sensitizer) and increased viability in a PC12 cell model. These results indicated that the neuroprotective effects of E2 in SCI are partly related to the suppression of excessive autophagy.