Department of Pharmacy, College of Pharmacy, Pusan National University, Geumjeong-gu, Busan, Republic of Korea.
Toxicol Lett. 2010 Mar 1;193(1):86-93. doi: 10.1016/j.toxlet.2009.12.015. Epub 2009 Dec 24.
Acrylamide (ACR) is a well-known neurotoxin in mammalian species that causes neuropathy characterized by ataxia and skeletal muscle weakness. Therefore, ACR-mediated axon damage in the central and peripheral nervous systems is considered to be central-peripheral axonopathy. However, the molecular mechanisms underlying ACR's toxicity to neural progenitor cells are unknown. This study investigated the adverse effects of ACR on mouse multipotent neural progenitor cells and adult hippocampal neurogenesis. ACR significantly reduced the proliferation of neural progenitor cells, and high ACR concentrations induced apoptotic and necrotic cell death. We found that elevated intracellular levels of reactive oxygen species were involved in ACR-mediated cytotoxicity. Interestingly, the administration of ACR to young mice resulted in a significant decrease in the number of newly generated cells in the dentate gyrus of the hippocampus, suggesting an impairment of adult neurogenesis. These results suggest that ACR's deleterious effects on the central nervous system are due to the death of neural progenitor cells and impaired adult neurogenesis.
丙烯酰胺（ACR）是一种在哺乳动物中已知的神经毒素，可引起以共济失调和骨骼肌无力为特征的周围神经病。因此，ACR 介导的中枢和周围神经系统轴突损伤被认为是中枢-周围轴突病。然而，ACR 对神经祖细胞毒性的分子机制尚不清楚。本研究探讨了 ACR 对小鼠多能神经祖细胞和成年海马神经发生的不良影响。ACR 显著降低了神经祖细胞的增殖能力，高浓度的 ACR 诱导细胞凋亡和坏死性细胞死亡。我们发现，细胞内活性氧水平的升高参与了 ACR 介导的细胞毒性。有趣的是，向幼鼠给予 ACR 导致海马齿状回中新生成的细胞数量显著减少，提示成年神经发生受损。这些结果表明，ACR 对中枢神经系统的有害影响是由于神经祖细胞的死亡和成年神经发生受损所致。
