Song Juhyun, Kang So Mang, Lee Kyoung Min, Lee Jong Eun
Department of Anatomy, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea.
Department of Anatomy, Yonsei University College of Medicine, Brain Korea 21 Project for Medical Science, 50 Yonsei-ro, Seodaemun-gu, Seoul 120-752, Republic of Korea ; BK21 Plus Project for Medical Sciences and Brain Research Institute, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
Biomed Res Int. 2015;2015:854359. doi: 10.1155/2015/854359. Epub 2015 Feb 1.
Stem cell therapy for tissue regeneration has several limitations in the fact that transplanted cells could not survive for a long time. For solving these limitations, many studies have focused on the antioxidants to increase survival rate of neural stem cells (NSCs). Melatonin, an antioxidant synthesized in the pineal gland, plays multiple roles in various physiological mechanisms. Melatonin exerts neuroprotective effects in the central nervous system. To determine the effect of melatonin on NSCs which is in LPS-induced inflammatory stress state, we first investigated nitric oxide (NO) production and cytotoxicity using Griess reagent assays, LDH assay, and neurosphere counting. Also, we investigated the effect of melatonin on NSCs by measuring the mRNA levels of SOX2, TLX, and FGFR-2. In addition, western blot analyses were performed to examine the activation of PI3K/Akt/Nrf2 signaling in LPS-treated NSCs. In the present study, we suggested that melatonin inhibits NO production and protects NSCs against LPS-induced inflammatory stress. In addition, melatonin promoted the expression of SOX2 and activated the PI3K/Akt/Nrf2 signaling under LPS-induced inflammation condition. Based on our results, we conclude that melatonin may be an important factor for the survival and proliferation of NSCs in neuroinflammatory diseases.
用于组织再生的干细胞疗法存在若干局限性，即移植的细胞无法长期存活。为了解决这些局限性，许多研究聚焦于抗氧化剂以提高神经干细胞（NSCs）的存活率。褪黑素是一种在松果体中合成的抗氧化剂，在多种生理机制中发挥多种作用。褪黑素在中枢神经系统中发挥神经保护作用。为了确定褪黑素对处于脂多糖（LPS）诱导的炎症应激状态下的神经干细胞的影响，我们首先使用格里斯试剂测定法、乳酸脱氢酶（LDH）测定法和神经球计数法研究了一氧化氮（NO）的产生和细胞毒性。此外，我们通过测量SOX2、TLX和FGFR-2的mRNA水平来研究褪黑素对神经干细胞的影响。另外，进行蛋白质免疫印迹分析以检测LPS处理的神经干细胞中PI3K/Akt/Nrf2信号通路的激活情况。在本研究中，我们表明褪黑素可抑制NO的产生，并保护神经干细胞免受LPS诱导的炎症应激。此外，在LPS诱导的炎症条件下，褪黑素促进了SOX2的表达并激活了PI3K/Akt/Nrf2信号通路。基于我们的研究结果，我们得出结论，褪黑素可能是神经炎症性疾病中神经干细胞存活和增殖的重要因素。
