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

被引:10
作者
Feng, Guo-Ying [1 ]
Liu, Jia [2 ]
Wang, You-Cui [3 ]
Wang, Zhen-Yu [4 ]
Hu, Yue [3 ]
Xia, Qing-Jie [3 ]
Xu, Yang [3 ]
Shang, Fei-Fei [3 ]
Chen, Mei-Rong [2 ]
Wang, Fang [2 ]
Zhou, Xue [1 ]
Wang, Ting-Hua [1 ,2 ,3 ,5 ]
机构
[1] Sichuan Univ, West China Sch Preclin & Forens Med, Dept Histol & Embryol, Chengdu 610041, Sichuan, Peoples R China
[2] Kunming Med Univ, Inst Neurosci, Kunming 650031, Peoples R China
[3] Sichuan Univ, Dept Anesthesia, Inst Neurol Dis, Translat Neurosci Ctr,State Key Lab Biotherapy,We, Chengdu 610041, Sichuan, Peoples R China
[4] Kunming Med Univ, Biomed Engn Res Ctr, Kunming 650031, Peoples R China
[5] Sichuan Univ, Dept Histol & Neurobiol, West China Sch Preclin & Forens Med, Chengdu 610041, Sichuan, Peoples R China
基金
中国国家自然科学基金;
关键词
Alpha-synuclein; Primary spinal neurons; Spinal cord transection; Apoptotic gene; Ciliary neurotrophic factor; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; ALZHEIMERS-DISEASE; LEWY BODIES; CELL-DEATH; RAT MODEL; INJURY; MECHANISMS; MICE; NEUROTOXICITY;
D O I
10.1007/s10571-016-0420-x
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
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 alpha-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.
引用
收藏
页码:817 / 829
页数:13
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