Lin Chao-Qun, Chen Lu-Kui
School of Medicine, Southeast University, Nanjing, Jiangsu Province, China.
School of Medicine, Southeast University, Nanjing, Jiangsu Province; Department of Neurosurgery, Cancer Center, Integrated Hospital of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong Province, China.
Neural Regen Res. 2020 Nov;15(11):2057-2062. doi: 10.4103/1673-5374.282262.
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, differentiation, 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, 5% CO, 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 environment. 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.
先前的研究发现，脑源性多巴胺神经营养因子（CDNF）对脑多巴胺能神经元具有保护作用，并且CDNF被视为神经退行性疾病的一种有前景的治疗药物。然而，CDNF对神经干细胞（NSC）的增殖、分化和凋亡的影响尚不清楚，而神经干细胞对缺氧环境非常敏感。在本研究中，从胎鼠海马中提取神经干细胞，并用不同浓度的CDNF进行培养。结果表明，在非缺氧环境条件下，200 nM的CDNF是显著提高神经干细胞活力的最佳浓度。然后，将细胞在90%N₂、5%CO₂和5%空气的缺氧条件下用200 nM的CDNF培养6小时。结果表明，CDNF显著提高了缺氧神经干细胞的活力，并减少了缺氧神经干细胞中的细胞凋亡。标志物检测表明，CDNF增加了缺氧神经干细胞向神经元和星形胶质细胞的分化。在缺氧条件下，CDNF还降低了神经干细胞中Lin28蛋白的表达水平，并增加了Let-7 mRNA的表达。总之，我们确定CDNF能够逆转通常在缺氧环境中影响神经干细胞的不良增殖、分化和凋亡效应。此外，Lin28/Let-7通路可能参与了CDNF的这种调节功能。本研究于2018年9月24日获得中国东南大学实验动物中心批准（批准号：20180924006）。
