title: Knockdown of α-synuclein in cerebral cortex improves neural behavior associated with apoptotic inhibition and neurotrophin expression in spinal cord transected rats.
abstract: 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.
authors.affiliation: Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, State Key Lab of Biotherapy, Sichuan University, Chengdu, 610041, China.
authors.forename: You-Cui
authors.initials: YC
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, State Key Lab of Biotherapy, Sichuan University, Chengdu, 610041, China.
authors.forename: Guo-Ying
authors.initials: GY
authors.lastname: Feng
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Qing-Jie
authors.initials: QJ
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China.
authors.forename: Liu-Lin
authors.initials: LL
authors.lastname: Xiong
authors.affiliation: Institute of Physical Education, Yunnan Normal University, Kunming, 650500, China.
authors.forename: Zhi-Wei
authors.initials: ZW
authors.lastname: Chen
authors.affiliation: Institute of Physical Education, Yunnan Normal University, Kunming, 650500, China.
authors.forename: Hang-Ping
authors.initials: HP
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, State Key Lab of Biotherapy, Sichuan University, Chengdu, 610041, China. tinghua_neuron@263.net.|Institute of Neuroscience, Kunming Medical University, Kunming, 650031, China. tinghua_neuron@263.net.|Department of Anesthesiology and Institute of Neurological Disease, Translational Neuroscience Center, West China Hospital, Sichuan University, Chengdu, 610041, China. tinghua_neuron@263.net.
authors.forename: Ting-Hua
authors.initials: TH
authors.lastname: Wang
authors.affiliation: Department of Histology and Embryology, West China School of Preclinical and Forensic Medicine, State Key Lab of Biotherapy, Sichuan University, Chengdu, 610041, China. zhouxue7239@163.com.
authors.forename: Xue
authors.initials: X
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002470:Cell Survival / Q000235:genetics*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005260:Female; D020932:Nerve Growth Factor / Q000096:biosynthesis; D009414:Nerve Growth Factors / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000235:genetics; D013116:Spinal Cord / Q000601:surgery; D013119:Spinal Cord Injuries / Q000473:pathology*; D051844:alpha-Synuclein / Q000096:biosynthesis / Q000235:genetics*; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis
chemical_list: D019208:Brain-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; C497606:Snca protein, rat; D051844:alpha-Synuclein; D051028:bcl-2-Associated X Protein; D020932:Nerve Growth Factor
keywords: Apoptosis; Cortical neuron; Motor and sensory function; Spinal cord transection; α-synuclein