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Effects of Alpha-Synuclein on Primary Spinal Cord Neurons Associated with Apoptosis and CNTF Expression

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Abstract

Spinal cord injury (SCI) often causes neurological deficits with poor recovery; the treatment, however, is far from satisfaction, and the mechanisms remain unclear. Using immunohistochemistry and western blotting analysis, we found α-synuclein (SNCA) was significantly up-regulated in the spinal caudal segment of rats subjected to spinal cord transection at 3 days post-operation. Moreover, the role of SNCA on neuronal growth and apoptosis in vitro was determined by using overexpressing and interfering SNCA recombined plasmid vectors, and the underlying mechanism was detected by QRT-PCR and western blotting. Spinal neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival, while it results in cell apoptosis in SNCA-ORF group. In molecular level, SNCA silence induced the up-regulation of CNTF and down-regulation of Caspase7/9. Together, endogenous SNCA plays a crucial role in spinal neuronal survival, in which the underlying mechanism may be linked to the regulation both apoptotic genes (Caspase7/9) and CNTF. The present findings therefore provide novel insights into the role of SNCA in spinal cord and associated mechanism, which may provide novel cue for the treatment of SCI in future clinic trials.

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Funding

This project was supported by Grants from National Natural Science Foundation of China (CN) (No. 81560215; 81171176), Ph.D. Programs Foundation of Ministry of Education of China (No. 20125317120001) and Yunnan Provincial Natural Science Foundation of China (No. 2011FZ112, 2013FZ134).

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    Authors and Affiliations

    1. Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China

      Guo-Ying Feng, Xue Zhou & Ting-Hua Wang

    2. Institute of Neuroscience, Kunming Medical University, Kunming, 650031, China

      Jia Liu, Mei-Rong Chen, Fang Wang & Ting-Hua Wang

    3. Department of Anesthesia, Institute of Neurological Disease, Translational Neuroscience Center, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China

      You-Cui Wang, Yue Hu, Qing-Jie Xia, Yang Xu, Fei-Fei Shang & Ting-Hua Wang

    4. Biomedical Engineering Research Center, Kunming Medical University, Kunming, 650031, China

      Zhen-Yu Wang

    5. Department of Histology and Neurobiology, West China School of Preclinical and Forensic Medicine, Sichuan University, Chengdu, 610041, Sichuan, China

      Ting-Hua Wang

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    1. Guo-Ying Feng
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    Guo-Ying Feng and Jia Liu are co-first authors and these authors have contributed equally to this work.

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    Feng, GY., Liu, J., Wang, YC. et al. Effects of Alpha-Synuclein on Primary Spinal Cord Neurons Associated with Apoptosis and CNTF Expression. Cell Mol Neurobiol 37, 817–829 (2017). https://doi.org/10.1007/s10571-016-0420-x

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