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Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats

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Abstract

17β-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.

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Acknowledgements

This work was supported by the Natural Science Foundation of Zhejiang Province, China (LY14H060009), National Natural Science Foundation of China (80215097), Science-technology Program of Wenzhou Municipal Sci-Tech Bureau, China (Y20150226) and the key Discipline Construction Project of Colleges and Universities in Zhejiang Province, China (2012-207).

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    1. Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China

      Chao-Wei Lin, Bi Chen, Ke-Lun Huang, Yu-Sen Dai & Hong-Lin Teng

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    1. Chao-Wei Lin
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    2. Bi Chen
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    Correspondence to Hong-Lin Teng.

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    Chao-Wei Lin and Bi Chen have contributed equally to this work.

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    Lin, CW., Chen, B., Huang, KL. et al. Inhibition of Autophagy by Estradiol Promotes Locomotor Recovery after Spinal Cord Injury in Rats. Neurosci. Bull. 32, 137–144 (2016). https://doi.org/10.1007/s12264-016-0017-x

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    • DOI: https://doi.org/10.1007/s12264-016-0017-x

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