Methylglyoxal Causes Cell Death in Neural Progenitor Cells and Impairs Adult Hippocampal Neurogenesis.
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.
['Chun|Hye Jeong|HJ|', 'Lee|Yujeong|Y|', 'Kim|Ah Hyun|AH|', 'Lee|Jaewon|J|']
D000818:Animals D001362:Avoidance Learning D019208:Brain-Derived Neurotrophic Factor D016923:Cell Death D049109:Cell Proliferation D002478:Cells, Cultured D006624:Hippocampus D020935:MAP Kinase Signaling System D008297:Male D008568:Memory D051379:Mice D008810:Mice, Inbred C57BL D058953:Neural Stem Cells D055495:Neurogenesis D011765:Pyruvaldehyde D017382:Reactive Oxygen Species D016708:Synaptophysin
Methylglyoxal Neural progenitor cells Hippocampal neurogenesis Memory retention Brain-derived neurotropic factor