Zhang Shan, Chen Shu, Liu Anmin, Wan Jungang, Tang Lingwen, Zheng Niandong, Xiong Yi
Department of Neurology, The People's Hospital of Leshan, Leshan 614000, Sichuan, China.
Department of Neurosurgery, The People's Hospital of Leshan, Leshan 614000, Sichuan, China.
Neurosci Lett. 2018 May 14;675:133-139. doi: 10.1016/j.neulet.2017.10.014. Epub 2017 Oct 13.
The neurotrophin brain-derived neurotrophic factor (BDNF) has been involved in supporting of neuron survival. The observation of reduced level of BDNF in the substantia nigra (SN) of Parkinson's disease (PD) patients suggests its important role in neuron protection in PD pathogenesis. However, the mechanism underlying the down-regulation of BDNF in PD was largely unknown. In this study, we found that miR-210-3p is involved in the regulation of BDNF production by 1-methyl-4-phenylpyridinium (MPP). MPP inhibits the BDNF production in SH-SY5Y cells through a transcription independent manner. Moreover, miR-210-3p, which targets BDNF mRNA, is up-regulated by MPP in SH-SY5Y cells. Importantly, inhibition of miR-210-3p prevents the reduction of BDNF production by MPP and improves the DA neuron survival in 1-methyl-4-phenyl-1,2,3,6-tetra hydropyridine (MPTP) model. Together, we demonstrated up-regulation of miR-210-3p by MPP reduces the BDNF production and contributes to the DA neuron damage.
神经营养因子脑源性神经营养因子（BDNF）参与支持神经元存活。帕金森病（PD）患者黑质（SN）中BDNF水平降低的观察结果表明其在PD发病机制中的神经元保护作用。然而，PD中BDNF下调的潜在机制在很大程度上尚不清楚。在本研究中，我们发现miR-210-3p参与1-甲基-4-苯基吡啶鎓（MPP）对BDNF产生的调控。MPP通过转录非依赖方式抑制SH-SY5Y细胞中BDNF的产生。此外，靶向BDNF mRNA的miR-210-3p在SH-SY5Y细胞中被MPP上调。重要的是，抑制miR-210-3p可防止MPP降低BDNF的产生，并改善1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）模型中多巴胺能神经元的存活。总之，我们证明MPP上调miR-210-3p会降低BDNF的产生并导致多巴胺能神经元损伤。
