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

• Published in: Neuroscience bulletin Vol. 32; no. 2; pp. 137 - 144
• Main Authors: Lin, Chao-Wei, Chen, Bi, Huang, Ke-Lun, Dai, Yu-Sen, Teng, Hong-Lin
• Format: Journal Article
• Language: English
• Published: Singapore Springer Singapore 01.04.2016; Springer
• Subjects: 17β-雌二醇; Anatomy; Anesthesiology; Animals; Autophagy - drug effects; Beclin-1 - genetics; Beclin-1 - metabolism; Biomedical and Life Sciences; Biomedicine; blot分析; Disease Models, Animal; Down-Regulation - drug effects; Estradiol; Estradiol - blood; Estradiol - pharmacology; Estradiol - therapeutic use; Estrogens - blood; Estrogens - pharmacology; Estrogens - therapeutic use; Female; Follow-Up Studies; Human Physiology; Hydrogen Peroxide - metabolism; Locomotion - drug effects; Microtubule-Associated Proteins - genetics; Microtubule-Associated Proteins - metabolism; Motor Neurons - drug effects; Nervous system diseases; Neurology; Neurosciences; Original; Original Article; Ovariectomy; Pain Medicine; PC12 Cells; Phenols; Rats; Rats, Sprague-Dawley; Recovery of Function - drug effects; Spinal cord injuries; Spinal Cord Injuries - drug therapy; Spinal Cord Injuries - pathology; 中枢神经系统疾病; 大鼠; 实时定量PCR; 神经保护作用; 脊髓损伤; 运动神经元; 17β-estradiol; Motor neuron; Spinal cord injury; Autophagy
• ISSN: 1673-7067; 1995-8218
• DOI: 10.1007/s12264-016-0017-x

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. Realtime PCR and western blot analysis revealed that the protective function of E2 was related to the suppression of LC3 II 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.