中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2020, Vol. 15 ›› Issue (11): 2057-2062.doi: 10.4103/1673-5374.282262

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

脑多巴胺神经营养因子可促进缺氧损伤神经干细胞的增殖和分化能力

  

  • 出版日期:2020-11-15 发布日期:2020-08-21
  • 基金资助:
    中国国家自然科学基金项目（81471780，81671819）

Cerebral dopamine neurotrophic factor promotes the proliferation and differentiation of neural stem cells in hypoxic environments

Chao-Qun Lin1 , Lu-Kui Chen1, 2   

  1. 1 School of Medicine, Southeast University, Nanjing, Jiangsu Province, China
    2 Department of Neurosurgery, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China
  • Online:2020-11-15 Published:2020-08-21
  • Contact: Lu-Kui Chen, PhD,neuro_clk@hotmail.com.
  • Supported by:
    This study was supported by the National Natural Science Foundation of China, Nos. 81471780 and 81671819 (both to LKC).

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摘要：

既往研究发现，脑多巴胺神经营养因子对脑多巴胺能神经元存在保护作用，且被认为是多种神经退行性疾病的潜在治疗药物。但其是否对缺氧环境十分敏感的神经干细胞的增殖、分化和凋亡发生影响，目前尚不可知。实验首先从胎鼠海马中提取了神经干细胞，以不同浓度的脑多巴胺神经营养因子进行培养，发现其中200 nM脑多巴胺神经营养因子是在非缺氧环境下提高神经干细胞活性的最佳浓度。然后以此浓度的脑多巴胺神经营养因子对细胞进行干预，并以90％N2、5％CO2和5％空气环境培养6h建立缺氧模型。结果显示，脑多巴胺神经营养因子可显著提高缺氧神经干细胞的活性，并减少缺氧神经干细胞的凋亡。通过标志物的检测说明脑多巴胺神经营养因子可恢复缺氧神经干细胞向神经元和星形胶质细胞分化的能力。同时还发现脑多巴胺神经营养因子能降低细胞缺氧神经干细胞中LIN28蛋白的表达，并促进Let-7mRNA表达。因此认为脑多巴胺神经营养因子可逆转缺氧对神经干细胞增殖、分化和凋亡的不利影响，且LIN28/Let-7信号通路可能参与脑多巴胺神经营养因子的调节作用。实验于2018-09-24经东南大学实验动物中心批准（批准号20180924006）。

orcid: 0000-0002-8075-8369 (Lu-Kui Chen)

关键词: 脑多巴胺神经营养因子, 缺氧, 神经干细胞, 细胞凋亡, 星形胶质细胞, 分化, LIN28, Let-7, 神经元, 增殖

Abstract: Previous research found that cerebral dopamine neurotrophic factor (CDNF) has a protective effect on brain dopaminergic neurons, and CDNF is regarded as a promising therapeutic agent for neurodegenerative diseases. However, the effects of CDNF on the proliferation, dif- ferentiation, and apoptosis of neural stem cells (NSCs), which are very sensitive to hypoxic environments, remain unknown. In this study, NSCs were extracted from the hippocampi of fetal rats and cultured with different concentrations of CDNF. The results showed that 200 nM CDNF was the optimal concentration for significantly increasing the viability of NSCs under non-hypoxic environmental conditions. Then, the cells were cultured with 200 nM CDNF under the hypoxic conditions of 90% N 2 , 5% CO 2 , and 5% air for 6 hours. The results showed that CDNF significantly improved the viability of hypoxic NSCs and reduced apoptosis among hypoxic NSCs. The detection of markers showed that CDNF increased the differentiation of hypoxic NSCs into neurons and astrocytes. CDNF also reduced the expression level of Lin28 protein and increased the expression of Let-7 mRNA in NSCs, under hypoxic conditions. In conclusion, we determined that CDNF was able to reverse the adverse proliferation, differentiation, and apoptosis effects that normally affect NSCs in a hypoxic environ- ment. Furthermore, the Lin28/Let-7 pathway may be involved in this regulated function of CDNF. The present study was approved by the Laboratory Animal Centre of Southeast University, China (approval No. 20180924006) on September 24, 2018.

Key words: apoptosis,  astrocyte, cerebral dopamine neurotrophic factor, differentiation, hypoxia, Let-7, Lin28, neural stem cells, neuron,
proliferation