Chun Hye Jeong, Lee Yujeong, Kim Ah Hyun, Lee Jaewon
Department of Pharmacy, College of Pharmacy, Molecular Inflammation Research Center for Aging Intervention, Pusan National University, Busan, 609-735, Republic of Korea.
Neurotox Res. 2016 Apr;29(3):419-31. doi: 10.1007/s12640-015-9588-y. Epub 2015 Dec 21.
Methylglyoxal (MG) is formed during normal metabolism by processes like glycolysis, lipid peroxidation, and threonine catabolism, and its accumulation is associated with various degenerative diseases, such as diabetes and arterial atherogenesis. Furthermore, MG has also been reported to have toxic effects on hippocampal neurons. However, these effects have not been studied in the context of neurogenesis. Here, we report that MG adversely affects hippocampal neurogenesis and induces neural progenitor cell (NPC) death. MG significantly reduced C17.2 NPC proliferation, and high concentration of MG (500 μM) induced cell death and elevated oxidative stress. Further, MG was found to activate the ERK signaling pathway, indicating elevated stress response. To determine the effects of MG in vivo, mice were administrated with vehicle or MG (0.5 or 1 % in drinking water) for 4 weeks. The numbers of BrdU-positive cells in hippocampi were significantly lower in MG-treated mice, indicating impaired neurogenesis, but MG did not induce neuronal damage or glial activations. Interestingly, MG reduced memory retention when administered to mice at 1 % but not at 0.5 %. In addition, the levels of hippocampal BDNF and synaptophysin were significantly lower in the hippocampi of mice treated with MG at 1 %. Collectively, our findings suggest MG could be harmful to NPCs and to hippocampal neurogenesis.
甲基乙二醛（MG）在正常代谢过程中通过糖酵解、脂质过氧化和苏氨酸分解代谢等过程形成，其积累与各种退行性疾病相关，如糖尿病和动脉粥样硬化。此外，据报道MG对海马神经元也有毒性作用。然而，这些影响尚未在神经发生的背景下进行研究。在此，我们报告MG对海马神经发生有不利影响并诱导神经祖细胞（NPC）死亡。MG显著降低了C17.2 NPC的增殖，高浓度的MG（500μM）诱导细胞死亡并升高氧化应激。此外，发现MG激活ERK信号通路，表明应激反应增强。为了确定MG在体内的作用，给小鼠饮用载体或MG（饮用水中0.5%或1%）4周。MG处理的小鼠海马中BrdU阳性细胞数量显著降低，表明神经发生受损，但MG未诱导神经元损伤或胶质细胞激活。有趣的是，以1%而非0.5%的剂量给小鼠施用MG时，会降低记忆保持能力。此外，在以1%的MG处理的小鼠海马中，海马脑源性神经营养因子（BDNF）和突触素水平显著降低。总的来说，我们的研究结果表明MG可能对NPC和海马神经发生有害。
