, Volume 21, Issue 4, pp 404–420 | Cite as

Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats

  • You-Cui Wang
  • Guo-Ying Feng
  • Qing-Jie Xia
  • Yue Hu
  • Yang Xu
  • Liu-lin Xiong
  • Zhi-wei Chen
  • Hang-Ping Wang
  • Ting-Hua WangEmail author
  • Xue ZhouEmail author


Spinal cord injury (SCI) often causes severe functional impairment with poor recovery. The treatment, however, is far from satisfaction, and the mechanisms remain unclear. By using proteomics and western blot, we found spinal cord transection (SCT) resulted in a significant down-regulation of α-synuclein (SNCA) in the motor cortex of SCT rats at 3 days post-operation. In order to detect the role of SNCA, we used SNCA-ORF/shRNA lentivirus to upregulate or knockdown SNCA expression. In vivo, SNCA-shRNA lentivirus injection into the cerebral cortex motor area not only inhibited SNCA expression, but also significantly enhanced neurons’ survival, and attenuated neuronal apoptosis, as well as promoted motor and sensory function recovery in hind limbs. While, overexpression SNCA exhibited the opposite effects. In vitro, cortical neurons transfected with SNCA-shRNA lentivirus gave rise to an optimal neuronal survival and neurite outgrowth, while it was accompanied by reverse efficiency in SNCA-ORF group. In molecular level, SNCA silence induced the upregulation of Bcl-2 and the downregulation of Bax, and the expression of NGF, BDNF and NT3 was substantially upregulated in cortical neurons. Together, endogenous SNCA play a crucial role in motor and sensory function regulation, in which, the underlying mechanism may be linked to the regulation of apoptosis associated with apoptotic gene (Bax, Bcl2) and neurotrophic factors expression (NGF, BDNF and NT3). These finds provide novel insights to understand the role of SNCA in cerebral cortex after SCT, and it may be as a novel treatment target for SCI repair in future clinic trials.


α-synuclein Spinal cord transection Cortical neuron Apoptosis Motor and sensory function 



We gratefully thank Jia Liu and Mei-rong Chen for assistance with the experiment and valuable discussion. This research was supported by a grant from National Natural Science Foundation of China (CN) (No. 81171176).

Compliance with ethical standards

Conflicts of interest

All authors declare that they have no conflict of interest.


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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • You-Cui Wang
    • 1
  • Guo-Ying Feng
    • 1
  • Qing-Jie Xia
    • 3
  • Yue Hu
    • 3
  • Yang Xu
    • 3
  • Liu-lin Xiong
    • 3
  • Zhi-wei Chen
    • 4
  • Hang-Ping Wang
    • 4
  • Ting-Hua Wang
    • 1
    • 2
    • 3
    Email author
  • Xue Zhou
    • 1
    Email author
  1. 1.Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, State Key Lab of BiotherapySichuan UniversityChengduChina
  2. 2.Institute of NeuroscienceKunming Medical UniversityKunmingChina
  3. 3.Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China HospitalSichuan UniversityChengduChina
  4. 4.Institute of Physical EducationYunnan Normal UniversityKunmingChina

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